ORIGINAL_ARTICLE
Renal injury, nephrolithiasis and Nigella sativa: A mini review
Objective: The incidence and prevalence of kidney stone is increasing worldwide. After the first recurrence the risk of subsequent relapses is higher and the time period between relapses is shortened. Urinary stones can be severely painful and make a huge economic burden. The stone disease may increase the vulnerability of patients to other diseases such as renal failure. Medicinal herbs are rich sources of antioxidants which are increasingly consumed globally for their safety, efficacy and low price. Nigella sativa is a spice plant that is widely used for prevention and treatment of many ailments in Muslim countries and worldwide. This review aims at investigation of the effects of Nigella sativa on renal injury and stone formation. Materials and Method: The scientific resources including PubMed, Scopus, and Google scholar were searched using key words such as: nephrolithiasis, urolithiasis, kidney/renal stone, renal injury, renal failure, urinary retention and black seed, black cumin, Nigella sativa and thymoquinone. Results: N. sativa and its main component, thymoquinone showed positive effects in prevention or curing kidney stones and renal failure through various mechanism such as antioxidative, anti-inflammatory, anti-eicosanoid and immunomodulatory effects. The putative candidate in many cases has been claimed to be thymoquinone but it seems that at least in part, particularly in kidney stones, the herbal melanin plays a role which requires further investigation to prove. Conclusion: N. sativa and its components are beneficial in prevention and curing of renal diseases including nephrolithiasis and renal damages.
https://ajp.mums.ac.ir/article_6020_b4fd3efc8a26ec54f5450e2c1fced37b.pdf
2016-01-01
1
8
10.22038/ajp.2016.6020
Nigella sativa L
Thymoquinone
Herbal melanin
nephrolithiasis
Renal failure
Parichehr
Hayatdavoudi
hayatdp891@mums.ac.ir
1
Neurocognitive research center & department of physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Abolfazl
Khajavi Rad
khajavirada@mums.ac.ir
2
Neurogenic inflammation research center & department of physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Ziba
Rajaei
rajaeiz@iums.ac.ir
3
Department of physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
AUTHOR
Mousa AL-Reza
Hadjzadeh
hajzadehmr@mums.ac.ir
4
Neurocognitive research center & department of physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Ahmed OG, El-Mottaleb NA, 2013. Renal function and arterial blood pressure alterations after exposure to acetaminophen with a potential role of Nigella sativa oil in adult male rats. J Physiol Biochem, 69: 1–13.
1
Ali B H, Blunden G. 2003. Pharmacological and Toxicological Properties of Nigella sativa. Phytother Res, 305: 299–305.
2
Alok S, Jain SK, Verma A, Kumar M, Sabharwal M. 2013. Pathophysiology of kidney , gallbladder and urinary stones treatment with herbal and allopathic medicine : A review. Asian Pac J Trop Dis, 3: 496–504. Anders HJ, Banas B, Schlondorff D. 2004. Signaling Danger : Toll-Like Receptors and their Potential Roles in Kidney Disease. J Am Soc Nephrol, 15: 854–867.
3
Awad AS, Kamel R., Sherief ME. 2011. Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine / spermine N-1-acetyl-transferase gene expression induced by renal ischaemia – reperfusion in rats. J Pharm Pharmacol, 63: 1037–1042.
4
Bayrak O, Bavbek N, Karatas OF, Bayrak R., Catal F, Cimentepe E, Akbas A, et al. 2008. Nigella sativa protects against ischaemia / reperfusion injury in rat kidneys. Nephrol Dial Transplant, 23: 2206–2212.
5
Chou Y, Li C, Hsu H, Chang W, Liu C. 2011. Renal function in patients with urinary stones of varying compositions. KJMS, 27:264–267.
6
Coe FL, Evan A, Worcester E. 2005. Kidney stone disease. J Clin Invest, 115:2598–2608.
7
Deepika A, Minu S, Surinder KS. 2013. The role of natural antioxidants as potential therapeutic agents in nephrolithiasis. Asian J Pharm Clin Res, 6: 1–6.
8
El-obeid A, Westermark B, Hassib A, Ponte F. 2006. Effect of herbal melanin on IL-8: A possible role of Toll-like receptor 4 (TLR4). Biochem Bioph Res Co, 344:1200–1206.
9
Fararh K M, Atoji Y, Shimizu Y, Takewaki T. 2002. Isulinotropic properties of Nigella sativa oil in Streptozotocin plus Nicotinamide diabetic hamster. Res Vet Sci, 73: 279–282.
10
Grases F, Costa-bauza A, Prieto R M. 2006. Renal lithiasis and nutrition. Nut J, 5: 1–7.
11
Hadjzadeh M R, Khoei A, Hadjzadeh Z. 2007. Ethanolic Extract of Nigella Sativa L Seeds on Ethylene Glycol-Induced Kidney Calculi in Rats. Urol J, 4: 86–90.
12
Hadjzadeh MR, Mohammadian N, Rahmani Z. 2008. Effect of Thymoquinone on Ethylene Glycol-Induced Kidney Calculi in Rats. Urol J, 5: 149–155.
13
Hadjzadeh MR, Khajavi-rad A, Rajaei Z, Tehranipour M, Monavar N. 2011. The preventive effect of N-butanol fraction of Nigella sativa on ethylene glycol-induced kidney calculi in rats. Pharmacogn Mag, 7: 338–343.
14
Hamed MA, Ali SA. 2013. Effects of black seed oil on resolution of hepato-renal toxicity induced by bromobenzene in rats. Eur Rev Med Pharmacol Sci, 17: 569–581.
15
Havakhah S, Sadeghnia HR., Hajzadeh MR, Mohammadian N, Shafiee S, Hosseinzadeh H, Mohareri N, et al. 2014. Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage.
16
IJBMS, 17: 986–992.
17
Heilberg IP 2000. Nephrology Dialysis Transplantation Update on dietary recommendations and medical treatment of renal stone disease. Nephrol Dial Transplant, 15: 117–123.
18
Irani D, Eshratkhah R, Amin-sharifi A. 2005. Efficacy of Extracorporeal shock wave lithotripsy Monotherapy in Complex Urolithiasis in the Era of Advanced Endourologic Procedures. Urol J, 2: 13–19.
19
Jayakar B. 2002. Anti-ulcer effect of Nigella sativa Linn . against gastric ulcers in rats. Curr Sci India, 82: 177–179.
20
Jonassen JA, Kohjimoto Æ Y, Scheid C R, Schmidt Æ M. 2005. Oxalate toxicity in renal cells. Urol Res., 33: 329–339.
21
Kanter M, Coskun O, Budancamanak M. 2005. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol, 11: 6684–8.
22
Karaolanis G, Lionaki S, Moris D, Palla V, Vernadakis S. 2014. Secondary hyperoxaluria : a risk factor for kidney stone formation and renal failure in native kidneys and renal grafts. Transplant Rev, 28: 182–187.
23
Khajavi rad A, Hadjzadeh MR, Monavvar N. 2008. Preventive effects of ethyl acetate fractions from aqueous and ethanolic extract of Nigella sativa L. seeds on calcium oxalate kidney stones in Wistar rats. Koomesh, 9: 123–132.
24
Khattab MM, Nagi MN. 2007. Thymoquinone Supplementation attenuates Hypertension and Renal Damage in Nitric Oxide deficient Hypertensive Rats. Phytother Res, 414: 410–414.
25
Liu X, Zheng J, Zhou H. 2011. TLRs as pharmacological targets for plant-derived compounds in infectious and inflammatory diseases. Int immunopharmacol, 11: 1451–1456.
26
Mckenzie G, Hall J. 2013. Management of stone disease. Surgery, 31: 354–361.
27
Merchant ML, Cummins T D, Wilkey D W, Salyer SA, Powell DW, Klein JB, Lederer ED. 2008. Proteomic analysis of renal calculi indicates an important role for inflammatory processes in calcium stone formation. Am J Physiol Renal Physiol, 295: 1254–1258.
28
Miyazawa K, Takahashi Y, Morita N, Moriyama MT, Kosaka T, Nishio M, Yoshimoto T, et al. 2012. Cyclooxygenase 2 and prostaglandin E 2 regulate the attachment of calcium oxalate crystals to renal epithelial cells. Int J Urol, 19: 936–943.
29
Moe OW. 2006. Kidney stones : pathophysiology and medical management. Lancet, 367:333–44.
30
Musa D, Dilsiz N, Gumushan H, Ulakoglu G, Bitiren M. 2015. Antitumor activity of an ethanol extract of Nigella sativa seeds Antitumor activity of an ethanol extract of Nigella sativa seeds. Biologia Bratisl, 56: 735–740.
31
Nouvenne A, Meschi T, Guerra A, Allegri F, Prati B, Borghi L. 2008. Dietary treatment of nephrolithiasis. Clin Cases Miner Bone Metab, 5: 135–141.
32
Oberg F, Haseeb A, Ahnfelt M, Ponte F. 2009. Herbal melanin activates TLR4 / NF-kB signaling pathway. Phytomedicine, 16: 477–484.
33
Oncalves RD, Sponchiado PO. 2005. Antioxidant Activity of the Melanin Pigment Extracted from Aspergillus nidulans. Biol Pharm Bull, 28: 1129–1131.
34
Pacioretty LM, Babish JG. 2011. Formulations containing thymoquinone for urinary health. Patent.
35
Ragheb A, Attia A, Eldin W S, Elbarbry F, Gazarin S, Shoker A. 2009. The Protective Effect of Thymoquinone, an Anti-oxidant and Anti-inflammatory Agent, against Renal Injury: A Review. Saudi J Kidney Dis Transpl, 20: 741–752.
36
Romero V, Akpinar H, Assimos DG. 2010. Kidney Stones : A Global Picture of Prevalence , Incidence , and Associated Risk Factors. Rev Urol, 12: 86–96.
37
Sayed-Ahmed MM, Nagi MN. 2007. Thymoquinone Supplementation Prevents The Development of Gentamicin-induced acute renal toxicity in rats. Clin Exp Pharmacol P, 34: 399–405.
38
Sayer JA, Moochhalab SH, Thomasb DJ. 2010. The medical management of urolithiasis. Brit J Med Surg Urol, 3: 87–95.
39
Stone JR, Knutson TL, Kang C. 2010. Bilateral obstructing renal stones: an uncommon cause of acute renal failure. Am J Emerg Med. 28: 5-6
40
Tozawa K, Yasui T, Okada A, Hirose M, Hamamoto S, Itoh Y, Kohri K. 2008. NF – kB activation in renal tubular epithelial cells by oxalate. Int J Urol, 15: 924–928.
41
Tsao K, Wu TL, Chang PY, Sun CF, Wu LL, Wu JT. 2007. Multiple Risk Markers for Atherogenesis Associated With Chronic Inflammation Are Detectable in Patients With Renal Stones. J Clin Lab Anal, 21: 426–431.
42
Ulu R, Dogukan A, Tuzcu M, Gencoglu H, Ulas M, Ilhan N, Muqbil I, et al. 2012. Regulation of renal organic anion and cation transporters by thymoquinone in cisplatin induced kidney injury. Food Chem Toxicol, 50: 1675–1679.
43
Vance S, Benghuzzi H, Wilson-Simpson F, Tucci M. 2008. Thymoquinone supplementation and its effect on kidney tubule epithelial cells in vitro. Biomed Sci Instrum, 44: 477–82.
44
ORIGINAL_ARTICLE
Gastrointestinal effects of Nigella sativa and its main constituent, thymoquinone: a review
Gastrointestinal (GI) diseases affect a large number of people all over the world. Uncontrolled acid secretion and occurrence of gastric ulcers are common disorders of GI tract which pose serious problems to human health. Many synthetic drugs have been used to treat GI disorders but a definite cure has not been discovered so far and the available medications cause several side effects. Nigella sativa (N. sativa) (Ranunculacea) has several therapeutic effects which are attributed to its constituents like nigellicine, nigellidine, thymoquinone, dithymoquinone, thymol and carvacrol. Several beneficial pharmacological properties of this plant such as anti-oxidant, anti-bacterial, anti-histaminic, anti-hypertensive, hypoglycemic, anti-fungal, anti-inflammatory, anti-cancer and immunomodulatory effects were reported and different therapeutic properties such as reliving bronchial asthma, jaundice, hydrophobia, paralysis, conjunctivitis, piles, skin diseases, anorexia, headache, dysentery, infections, obesity, back pain, hypertension and gastrointestinal problems, have been described for the seeds of N. sativa and its oil. The present review provides a detailed summery of scientific researches regarding gastrointestinal effect of N. sativa and its main constituent, thymoquinone.
https://ajp.mums.ac.ir/article_4695_fcf0aa8ffbeb64177330b14f9252fdd2.pdf
2016-01-01
9
20
10.22038/ajp.2016.4695
Nigella Sativa
Gastrointestinal disease
Thymoquinone
Farzaneh
Shakeri
shakerif911@mums.ac.ir
1
Neurogenic Inflammation Research Centre and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Iran
AUTHOR
Zahra
Gholamnezhad
2
Neurogenic Inflammation Research Centre and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Iran
AUTHOR
Bruno
Mégarbane
3
Department of Medical and Toxicological Critical Care, Paris-Diderot University, INSERM U1144, Paris, France
AUTHOR
Ramin
Rezaee
rezaeer871@mums.ac.ir
4
Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
AUTHOR
Mohammad Hosein
Boskabady
boskabadymh@mums.ac.ir
5
Neurogenic Inflammation Research Centre and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Iran
LEAD_AUTHOR
Abdel-Wahab WM. 2013. Protective effect of thymoquinone on sodium fluoride-induced hepatotoxicity and oxidative stress in rats. J Basic Appl Zool, 66:263-270.
1
Abdel Sater KA. 2009. Protective effect of Nigella sativa oil on stress gastric ulcer in hypothyroidal rats. Internet J Nutr Wellness, 7:314-324.
2
Adel A-M, Morsy BM, Mahmoud AM, Abo-Seif MA, Zanaty MI. 2013. Beneficial therapeutic effects of Nigella sativa and/or Zingiber officinale in HCV patients in Egyp.EXCLI J, 12:943-955.
3
Al-Ghamdi M. 2001. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol, 76:45-48.
4
Al Mofleh, Ibrahim A, Alhaider, Abdulqader A, Mossa, Jaber S, Al-Sohaibani, Mohammed O, Al-Yahya, Mohammed A, Rafatullah, Syed Shaik, Shaffi A. 2008. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi J Gastroenterol, 14:128-34.
5
Awad AS, Kamel R, Sherief MAE. 2011. Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N‐1‐acetyl‐transferase gene expression induced by renal ischaemia–reperfusion in rats. J Pharm Pharacol, 63:1037-1042.
6
Bamosa AO, Kaatabi H, Lebda FM, Elq A-MA, Al-Sultan A. 2010. Effect of Nigella sativa seeds on the glycemic control of patients with type 2 diabetes mellitus.Indian J Physiol Pharmacol, 54:344-54.
7
Banerjee S, Kaseb AO, Wang Z, Kong DM, Mussop P, Subhash S, Fazlul HM, Ramzi M. 2009. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res, 69:5575-5583.
8
Boka J, Mahdavi A, Samie A, Jahanian R. 2014. Effect of different levels of black cumin (Nigella sativa L.) on performance, intestinal Escherichia coli colonization and jejunal morphology in laying hens. J Anim Physiol Anim Nutr, 98:373-383.
9
Boskabady M, Mohsenpoor N, Takaloo L.2010. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicin, 17:707-713.
10
Burits M, Bucar F. 2000. Antioxidant activity of Nigella sativa essential oil. Phytotherapy Research, 323-8.
11
Chaturvedi P, Singh AP, Moniaux N, Senapati S, Chakraborty S, Meza JL, Batra SK. 2007. MUC4 mucin potentiates pancreatic tumor cell proliferation, survival, and invasive properties and interferes with its interaction to extracellular matrix proteins. Mol Cancer Res, 5:309-320.
12
ChehlN, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. 2009. Anti‐inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB, 11:373-381.
13
Coban S, Yildiz F, Alpaslan Al, Behcet A, Nurten B, MuharremC. 2010. The effects of Nigella sativa on bile duct ligation induced‐liver injury in rats. Cell Biochem Funct, 28:83-88.
14
Daba MH, Abdel-Rahman MS. 1998. Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol Lett, 95:23-29.
15
Dehkordi FR, Kamkhah AF. 2008. Antihypertensiveeffect of Nigella sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol, 22:447-452.
16
El-Abhar H, Abdallah D, Saleh S. 2003. Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. J Ethnopharmacol, 84:251-258.
17
El-Dakhakhny M, Barakat M, El-Halim MA, Aly S. 2000. Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J Ethnopharmacol, 72:299-304.
18
El-Masry TA, Elahwel AM, Emara AM. 2010. Study on treating ethanol-induced gastric lesions with omeprazole, Nigella sativa oil, or both. Toxicol Environ Chem, 92:1765-1782.
19
El-Tahir KE-DH, Bakeet DM. 2006. The black seed Nigella sativa Linnaeus-A mine for multi cures: a plea for urgent clinical evaluation of its volatile oil. J Taibah Univ Med Sci, 1:1-19.
20
Emekli-Alturfan E, Yarat A, Tunali-Akbay T, Isik F, Yenidogan G, Sener G, Sehirli O, Pisiriciler R, Altintas A. 2011. Effect of Black Cumin (Nigella Sativa) Seed Oil on Gastric Tissue in Experimental Colitis. Adv Environ Biol, 5:483-90.
21
Farrag A, Mahdy KA, Abdel RG, Osfor MM. 2007. Protective effect of Nigella sativa seeds against lead-induced hepatorenal damage in male rats. Pak J Biol Sci, 10:2809-2816.
22
Gali-Muhtasib H, Diab-Assaf M, Boltze C, Al-Hmaira J, Hartig R, Roessner A, Schneider-Stock R. 2004. Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int J Oncol, 25:857-866 .
23
Gholamnezhad Z, Boskabady MH, Hosseini M. 2014. Effect of Nigella sativa on immune response in treadmill exercised rat. BMC Complement Altern Med, 14:437.
24
Gholamnezhad Z, Keyhanmanesh R, Boskabady MH. 2015. Anti-inflammatory, antioxidant, and immunomodulatory aspects of Nigella sativa for its preventive and bronchodilatory effects on obstructive respiratory diseases: A review of basic and clinical evidence. J Funct Food, 17:910-27.
25
Goreja WG. 2003. Black seed:nature's miracle remedy (papreback). Karger Publishers. pp. 1-51,New York.
26
Helal GK. 2010. Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. Pak J Pharm Sci, 23:131-137.
27
Isik F, Akbay TT, Yarat A, Genc Z, Pisiriciler R, Caliskan-Ak E, Cetinel S, Altıntas A, Sener G. 2011. Protective effects of black cumin (Nigella sativa) oil on TNBS-induced experimental colitis in rats. Dig Dis Sci, 56:721-730.
28
Islam S, Ahsan M, Hassan CM, Malek MA. 1989. Antifungal activities of the oils of Nigella sativa seeds. Pak J Pharm Sci, 2:25-28.
29
Kanter M, Coskun O, Budancamanak M. 2005a. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbontetrachloride-treated rats. World J Gastroenterol, 11:6684-8.
30
Kanter M, Coskun O, Uysal H. 2006. The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol, 80:217-224.
31
Kanter M, Demir H, Karakaya C, Ozbek H. 2005b. Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol, 11:6662-6.
32
KapanM,Tekin R, Onder A, Firat U, Evliyaoglu O, Taskesen F, Arikanoglu Z. 2012. Thymoquinone ameliorates bacterial translocation and inflammatory response in rats with intestinal obstruction. Int J Surg, 10:484-488.
33
Magdy M-A, Hanan E-A, Nabila E-M. 2012. Thymoquinone: Novel gastroprotective mechanisms. Eur J Pharmacol, 697:126-131.
34
Mahgoub AA. 2003. Thymoquinone protects against experimental colitis in rats. Toxicol Lett, 143:133-143.
35
Mahmoud M, El-Abhar H, Saleh S. 2002. The effect of Nigella sativa oil against the liver damage induced by Schistosoma mansoni infection in mice. J Ethnopharmacol, 79:1-11.
36
Mahmoud SS, Torchilin VP. 2013. Hormetic/cytotoxic effects of Nigella sativa seed alcoholic and aqueous extracts on MCF-7 breast cancer cells alone or in combination with doxorubicin. Cell Biochem Biophys, 66:451-460.
37
Majdalawieh AF, Hmaidan R, Carr RI. 2010. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol, 131:268-275.
38
Mantle D, Pickering AT, Perry EK. 2000. Medicinal plant extracts for the treatment of dementia. CNS drugs, 13:201-213.
39
Mohamed AM, Metwally NM, Mahmoud SS. 2005. Sativa seeds against Schistosoma mansoni different stages. Mem Inst OswaldoCruz,100:205-211.
40
Mohammed SS, Naim MM, Mahmoud SH. 2010. Possible Protective Effect of Nigella Sativa Oil Against Piroxicam‐Induced Gastric Mucosal Damage in Adult Male Albino Rats (Light and Scanning Electron Microscopic Study). Egypt J Histo, 33:127-139.
41
Morsi NM. 1999. Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Micro biol Pol, 49:63-74.
42
Nagi MN, Alam K, Badary OA, Al‐Shabanah OA, Al‐Sawaf HA, Al‐Bekairi AM. 1999. Thymoquinone protects against carbon tetrachloride hetatotoxicity in mice via an antioxidant mechanism. Int Biochem Mol Biol, 47:153-9.
43
Nagi MN, Almakki HA, Sayed-Ahmed MM, Al-Bekairi AM. 2010. Thymoquinone supplementation reverses acetaminophen-induced oxidative stress, nitric oxide production and energy decline in mice liver. Food Chem Toxicol, 48:2361-5.
44
Nili-Ahmadabadi A, Tavakoli F, Hasanzadeh G, Rahimi H, Sabzevari O. 2011. Protective effect of pretreatment withthymoquinone against Aflatoxin B1 induced liver toxicity in mice. Daru J Pharm Sci, 19:282-7.
45
Payment P. 1997. Epidemiology of endemic gastrointestinal and respiratory diseases: Incidence, fraction attributable to tap water and costs to society. Water Sci Technol, 35:7-10.
46
Raza M, Alghasham AA, Alorainy MS, El-Hadiyah TM. 2008. Potentiation of valproate-induced anticonvulsant response by Nigella sativa seed constituents: the role of GABA receptors. Int J health Sci, 2:15.
47
Rifat-uz-Zaman MSA, Khan MS. 2004. Gastroprotective and anti-secretory effect of Nigella sativa seed and its extracts in indomethacin-treated rats. Pak J Biol Sci, 7:995-1000.
48
Rooney S, Ryan M. 2005. Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Anticancer Res, 25:4255-4259.
49
Salem EM, Yar T, Bamosa A, Al-Quorain A, Yasawy MI, Alsulaiman RM, Randhawa MA. 2010. Comparative study of Nigella Sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia. Saudi J Gastroenterol, 16:207-214.
50
Salim EI, Fukushima S. 2003. Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis. Nutr cancer, 45:195-202.
51
Sayed-Ahmed MM, Aleisa AM, Al-Rejaie SS, Al-Yahya AA, Al-Shabanah OA, Hafez MM, Nagi MN. 2010. Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling. Oxid Med Cell Longev, 3:254-261.
52
Sharma PC, Yelne MB, Dennis TG. 2001. Database on medicinal plants used in Ayurveda. pp. 420-440, New Delhi.
53
Shenawy E, Nahla S, Soliman MF, Reyad SI. 2008. The effect of antioxidant properties of aqueous garlic extract and Nigella sativa as anti-schistosomiasis agents in mice. Rev Inst Med Trop São Paulo, 50:29-36.
54
Singh AP, Moniaux N, Chauhan SC, Meza JL, Batra SK. 2004. Inhibition of MUC4 expression suppresses pancreatictumor cell growth and metastasis. Cancer Res, 64:622-30.
55
Suddek GM. 2014. Protective role of thymoquinone against liver damage induced by tamoxifen in female rats. Can J Physiol Pharmacol, 92:640-4.
56
Suguna P, Geetha A, Aruna R, Siva GV. 2013. Effect of thymoquinone on ethanol and high fat diet induced chronic pancreatitis a dose response study in rats. Indian J Exp Biol, 51:292-302.
57
Torres MP, Ponnusamy MP, Chakraborty S, Smith LM, Das S, Arafat HA, Batra SK. 2010. Effects of thymoquinonein the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies. Mol Cancer Ther, 9:1419-1431.
58
Yildiz F, Coban S, Terzi A, Ates M, Aksoy N, Cakir H, Ocak AR, Bitiren M. 2008. Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver. World J Gastroenterol, 14:5204-9.
59
ORIGINAL_ARTICLE
A review on the inhibitory potential of Nigella sativa against pathogenic and toxigenic fungi
Nigella sativa (N. sativa) grows in various parts of the world, particularly in Iran. It has been traditionally used as a folk remedy to treat a number of diseases. The seeds of this plant contain moisture, proteins, carbohydrates, crude fiber, alkaloids, saponins, ash, fixed oils and essential oil. The major components of the essential oil are thymoquinone, p-cymene, trans-anethole, 2-methyl-5(1-methyl ethyl)-Bicyclo[3.1.0]hex-2-en and γ-terpinene. So far, several pharmacological effects such as anti-oxidant, anti-inflammatory, anti-cancer and anti-microbial have been reported for N. sativa or its active compounds. Thymoquinone, thymohydroquinone and thymol are the most active constituents which have different beneficial properties. The oil, extracts and some of N. sativa active components possessed moderate in vitro and in vivo inhibitory activity against pathogenic yeasts, dermatophytes, non-dermatophytic filamentous fungi and aflatoxin-producing fungi. The main morphological changes of pathogenic and toxigenic fungi treated with N. sativa oil were observed in the cell wall, plasma membrane and membranous organelles, particularly in the nuclei and mitochondria. Although this review represents first step in the search for a new anti-fungal drug, the full potential of N. sativa as a fungitoxic agent has not been exploited and necessitates further investigations.
https://ajp.mums.ac.ir/article_6190_797eb9e0832118bc85ab47d66b2eb856.pdf
2016-01-01
21
33
10.22038/ajp.2016.6190
Nigella Sativa
Thymoquinone
Antifungal and anti-aflatoxigenic activity
Yeast
Dermatophyte
Aspergillus
Hojjatollah
Shokri
hshokri@ut.ac.ir
1
Faculty of Veterinary Medicine, Amol University of Special Modern Technologies, Amol, Iran
LEAD_AUTHOR
Abdel-Wahhab MA, Aly SE. 2005. Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis. J Appl Toxicol, 25: 218-223.
1
Adamu HM, Ekanem EO, Bulama S. 2010. Identification of essential oil components from Nigella sativa seed by gas chromatography-mass spectroscopy. Pak J Nutr, 9: 966-967.
2
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
3
Al-Ghasham A, Ata HS, El-Deep S, Meki A, Shehada S. 2008. Study of protective effect of date and Nigella sativa on aflatoxin B1 toxicity. Int J Health Sci, 2: 26-44.
4
Ali B, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. Phytother Res, 17: 299-305.
5
Ali Z, Ferreira D, Carvalho P, Avery MA, Khan IA. 2008. Nigellidine-4-O-sulfite, the first sulfated indazole-type alkaloid from the seeds of Nigella sativa. J Nat Prod, 71: 1111-1112.
6
Aljabre SH, Randhawa MA, Akhtar N, Alakloby OM, Alqurashi AM, Aldossary A. 2005. Antidermatophyte activity of ether extract of Nigella sativa and its active principle, thymoquinone. J Ethnopharmacol, 101: 116-119.
7
Al-Jassir MS. 1992. Chemical composition and microflora of black cumin (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chem, 45: 239-242.
8
Al Saleh IA, Billedo G, Inam IE. 2006. Level of selenium, DL-α-tocopgerol, DL-γ- tocopherol, all trans retinol, thymoquinone and thymol in different brands of Nigella sativa seeds. J Food Comp Anal, 19: 167-175.
9
Amara AA, El-Masry MH, Bogdady HH. 2008. Plant crude extracts could be the solution: extracts showing in vivo antitumorigenic activity. Pak J Pharm Sci, 21: 159-171.
10
Asdadi A, Harhar H, Gharby S, Bouzoubaâ Z, Yadini AE, Moutaj R, Hadek ME, Chebli B, Hassani LMI. 2014. Chemical composition and antifungal activity of Nigella Sativa L. oil seed cultivated in Morocco. Int J Pharma Sci Invent, 3: 9-15.
11
Atta MB. 2003. Some characteristics of Nigella (Nigella sativa L.) seed cultivated in Egypt and its lipid profile. Food Chem, 83: 63-68.
12
Atta-Ur-Rahman. 1995. Nigellidine-a new indazole alkaloid from the seed of Nigella sativa. Tetrahedron Lett, 36: 1993-1994.
13
Badary OA, Abdel-Naim AB, Abdel-Wahab MH, Hamada FM. 2000. The influence of thymoquinone on doxorubicin-induced hyperlipidemic nephropathy in rats. Toxicol, 143: 219-226.
14
Boskabady MH, Mohsenpoor N, Takaloo L. 2010. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomed, 17: 707-713.
15
Bathnagar D, Garcia S. 2001. Aspergillus. In Labbe RG, Garcia S. (Eds.), Guide to Foodborne Pathogens. New York: John Wiley and Sons, pp. 35-49.
16
Burits M, Bucar F. 2000. Anti-oxidant activity of Nigella sativa oil. Phytother Res, 14: 323-328.
17
Cavaleiro C, Pinto E, Goncalves MJ, Salgueiro L. 2006. Antifungal activity of Juniperus essential oils against dermatophyte, Aspergillus and Candida strains. J Appl Microbiol, 100: 1333-1338.
18
Cheikh-Rouhou S, Besbes S, Lognay G, Blecker C, Deroanne C, Attia H. 2008. Sterol composition of black cumin (Nigella sativa L.) and Aleppo pine (Pinus halpensis Mill.) seed oils. J Food Comp Anal, 21: 162-168.
19
Cosentino S, Tuberoso CIG, Pisano B. 1999. In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils. Lett Appl Microbiol, 29: 130-136.
20
Daferera DJ, Zirgas BN, Polission MG. 2000. GC-MS analysis of essential oil from some Greek aromatic plants and their fungitoxicity on Penicillium digitatum. J Agric Food Chem, 48: 2576-2581.
21
Douglas LJ. 2003. Candida biofilms and their role in infection. Trends Microbiol, 11: 30-36.
22
Duarte MCT, Figueira GM. 2008. Anti-Candida activity of essential oils and extracts from native and exotic medicinal plants used in Brazil. In: Rai MK, Carpinella C. (Eds.), Naturally Occurring Bioactive Compounds: A Newer and Safer Alternative for Control of Pest and Diseases. The Haworth Press Inc.
23
El-Nagerabi SAF, Al-Bahry SN, Elshafie AE, Al-Hilali S. 2012. Effect of Hibiscus sabdariffa extract and Nigella sativa oil on the growth and aflatoxin B1 production of Aspergillus flavus and Aspergillus parasiticus strains. Food Control, 25: 59-63.
24
El-Tahir KE, Bakheet DM. 2007. The black seed Nigella sativa linnaeus-a mine for multi-cures: A plea for urgent clinical evaluation of its volatile oil. J T U Med Sci, 1: 1-19.
25
El-Wakil SS. 2007. Evaluation of the in vitro effect of Nigella sativa aqueous extract on Blastocystis hominis isolates. J Egypt Soc Parasitol, 7: 801-813.
26
Fan JJ, Chen.JH. 1999. Inhibition of aflatoxin-producing by welsh onion extracts. J Food Prot, 62: 414-417.
27
Feldmesser M. 2003. New and emerging antifungal agents: Impact on respiratory infections. Am J Respir Med, 2: 371-383.
28
Fierro M, Fidalgo CB. 1996. The involvement of nitrous oxide in the anti-Candida albicans activity of rat neutrophils. Immunol, 89: 295-300.
29
Iheshiulor OOM, Esonu BO, Chuwuka OK, Omede AA, Okoli IC, Ogbuewu IP. 2011. Effects of mycotoxins in animal nutrition. Asian J Anim Sci, 5: 19-33.
30
Junemann M. 1998. Three great healing herbs, Lotus Light Publications, Twin Laked,WI, pp. 45.
31
Gerige SJ, Gerige MKY, Rao M. 2009. GC-MS Analysis of Nigella sativa seeds and antimicrobial activity of its volatile oil. Braz Arch Biol Technol, 52: 1189-1192.
32
Geweely NS, Alakilli SYM. 2012. Effect of the purification of antidermatophytic proteins from Nigella sativa on four zoophilic species. Afr J Biotechnol, 11: 9422-9434.
33
Golparvar AR, Ghaisari MM, Hadipanah A, Armin A. 2013. Chemical analysis and identification of the components of black seed and Thyme cultivated in Iran. Sci Agri, 4: 55-57.
34
Goreja WG. 2003. Black seed: Nature's Miracle Remedy, Amazing Herbs Press, New York, NY.
35
Gupta S, Satishkumar MN, Duraiswamy B, Das S, Chhajed M. 2012. Potential herbs and its phytoconstituents against fungal infection: A systematic review. World J Pharma Res, 1: 1-20.
36
Halamova K, Kokoska L, Flesar J, Sklenickova O, Svobodova B, Marsik P. 2010. In vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levels. J Food Prot, 73: 2291-2295.
37
Hussein SY, Mekkawy IAA, Moktar ZZ Mubarak M. 2000. Protective effect of Nigella sativa seed against aflatoxicosis in Oreochromis niloticus. Proc. Conf. Mycotoxins and Dioxins and the Environment, Bydgoszcz, 25-27 Sept., pp: 109-130.
38
Ivankovic SR, Stojkovic M, Jukic M, Milos M. 2006. The antitumor activity of thymoquinone and thymohydroquinone in vitro and in vivo. Exp Oncol, 28: 220-224.
39
Kauffman CA. 2006. Fungal infections. Proc Am Thorac Soc, 3: 35-40.
40
Khan MA, Ashfaq MK, Zuberi HS, Zuberi AH. 2003. The in vivo anti-fungal activity of the aqueous extract from Nigella sativa seed. Phytother Res, 17: 183-186.
41
Khosravi AR, Minooeianhaghighi MH, Shokri H, Emami SA, Alavi SM, Asili J. 2011. The potential inhibitory effect of Cuminum cyminum, Ziziphora clinopodioides and Nigella sativa essential oils on the growth of Aspergillus fumigatus and Aspergillus flavus. Braz J Microbiol, 42: 216-224.
42
Khosravi AR, Shokri H, Farahnejat Z, Chalangari R, Katalin M. 2013. Antimycotic efficacy of Iranian medicinal plants towards dermatophytes obtained from patients with dermatophytosis. Chinese J Nat Med, 11: 43-48.
43
Khosravi AR, Shokri H, Minooeianhaghighi M. 2011. Inhibition of aflatoxin production and growth of Aspergillus parasiticus by Cuminum cyminum, Ziziphora clinopodioides, and Nigella sativa essential oils. Foodborne Pathog Dis, 8: 1275-1280.
44
Kumar R, Mishra AK, Dubey NK, Tripathi YB. 2007. Evaluation of Chenopodium ambrosioides as a potential source of antifungal, antiaflatoxigenic and antioxidant activity. Int J Food Microbiol, 115: 159-164.
45
Mahmoudvand H, Sharifi I, Fasihi Harandi M, Shokohi M, Shakibaie M, Rezaei Riabi T. 2014. Anti-leishmania effects of methotrexate (MTX) alone and incombination with meglumine antimoniate (MA) against Iranian isolate of sensitive and MA-resistant Leishmania tropica: an in-vitro assay. Asian Pac J Trop Med, 4: 412-420.
46
Mahmoud MR, El-Abhar HS, Saleh S. 2002. The effects of Nigella sativa oil against the liver damage induced by Schistosoma mansoni in mice. J Ethnopharmacol, 79: 1-11.
47
Maraqa A, Al-Sharoa NF, Farah H, Elbjeirami WM, Shakya AK, Sallal AJ. 2007. Effect of Nigella sativa extract and oil on aflatoxin production by Aspergillus flavus. Turk J Biol, 31: 155-159.
48
Mariam A, Al-Basal A. 2009. In vitro and in vivo anti-microbial effects of Nigella sativa Linn. seed extracts against clinical isolates from skin wound infections. Am J Appl Sci, 6: 1440-1447.
49
Martinez-Rossi NM, Peres NTA, Rossi A. 2008. Antifungal resistance mechanisms in dermatophytes. Mycopathologia, 166: 369-383.
50
Mehta BK, Pandit V, Gupta M. 2009. New principles from seeds of Nigella sativa. Nat Prod Res, 23: 138-148.
51
Morikawa T, Xu F, Ninomiya K, Matsuda H, Yoshikawa M. 2004. N. mines A3, A4, A5 and C, new dolabellane-type diterpene alkaloids with lipid metabolism-promoting activities from the Egyptian medicinal food black cumin. Chem Pharm Bull, 52: 494-497.
52
Naeini A, Khosravi AR, Chitsaz M, Shokri H, Kamlnejad M. 2009. Anti-Candida albicans activity of some Iranian plants used in traditional medicine. J Mycol Méd, 19: 168-172.
53
Nasir Z, Abid AR, Hayat Z, Shakoor HI. 2005. Effect of kalongi (Nigella sativa) seeds on egg production and quality in white Leghorn layers. J Anim Plant Sci, 15: 22-24.
54
Nergiz C, Otles S. 1993. Chemical composition of Nigella sativa L. seeds. Food Chem, 48: 259-261.
55
Nickavar B, Mojab F, Javidnia K, Amoli MA. 2003. Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Z Naturforsch C, 58: 629-631.
56
Ouraïni D, Agoumi A, Ismaili-Alaoui M, Alaoui K, Cherrah Y, Alaoui MA, Belabbas MA. 2007. Activité antifongique de l’acide oléique et des huiles essentielles de Thymus saturejoides L. et de Mentha pulegium L., comparée aux antifongiques dans les dermatoses mycosiques. Phytothér, 5: 6-14.
57
Ozmen A, Gamze B, Tugba A. 2007. Antimitotic and antibacterial effects of the Nigella sativa L Seed. Cayologial, 60: 270-272.
58
Pina-Vaz C, Rodrigues AG, Pinto E, Costa-de-Oliveira S, Tavares C, Salgueiro LR, Cavaleiro C, Goncalves MJ, Martinez-de-Oliveira J. 2004. Antifungal activity of Thymus oils and their major compounds. J Eur Acad Dermatol, 18: 73-78.
59
Pinto E, Palmeira A, Salgueiro L, Cavaleiro C, Goncalves MJ, Pina-Vaz C, Rodrigues A, Oliveira S. 2003. Antifungal activity of oregano oils (Lippia graveolens and Origanum virens) on dermatophyte species. Clin Microbiol Infec, 9: 222-230.
60
Rapp RP. 2004. Changing strategies for the management of invasive fungal infections. Pharmacother, 24: 4S-28S.
61
Rasooli I, Razzaghi-Abyaneh M. 2004. Inhibitory effects of thyme oils on growth and aflatoxin production by Aspergillus parasiticus. Food Control, 1: 479-483.
62
Raval BP, Shah TG, Suthar MP, Ganure AL. 2010. Screening of Nigella Sativa Seeds for antifungal activity. Ann Biolog Res, 1: 164-171.
63
Rchid H, Chevassus H, Nmila R, Guiral C, Petit P, Chokairi M. 2004. Nigella sativa seed extracts enhance glucose-induced insulin release from rat-isolated langerhans islets. Fundam Clin Pharmacol, 18: 525-529.
64
Randhawa MA, Al-Ghamdi MS. 2002. A review of the pharmacothera peutic effects of Nigella sativa. Pak J Med Res, 41: 77-83.
65
Rogozhin EA, Oshchepkova YI, Odintsova TI, Khadeeva NV, Veshkurova ON, Egorov TA. 2011. Novel antifungal defensins from Nigella sativa L. seeds. Plant Physiol Biochem, 49: 131-137.
66
Roze LV, Koptina AV, Laivenieks M, Beaudry RM, Jones DA, Kanarsky AV, Linz JE. 2011. Willow volatiles influence growth, development, and secondary metabolism in Aspergillus parasiticus. Appl Microbiol Biotechnol, 92: 359-370.
67
Sakuda S, Ono M, Ikeda H, Nakamura T, Inagaki Y, Kawachi R, Nakayama J, Suzuki A, Isogai A, Nagasawa H. 2000. Blasticidin A as an inhibitor of aflatoxin production by Aspergillus parasiticus. J Antibiotics, 68: 407-412.
68
Salem ML 2005. Immunomodulatory and therapeutic properties of the Nigella Sativa L. Seed. Int Immunopharmacol, 5: 1749-1770.
69
Shigeharu I, Katsuhisa U, Toshio T, Hideyo Y, Shigeru A. 2006. Evaluation of the effect of terpenoid quinones on Trichophyton mentagrophytes by solution and vapor contact. J Infect Chemother, 12: 100-104.
70
Shohayeb M, Halawani E. 2012. Comparative antimicrobial activity of some active constituents of N. sativa L. World Appl Sci J, 20: 182-189.
71
Shokri H, Sharifzadeh A, Ashrafi Tamai I. 2012. Anti-Candida zeylanoides activity of some Iranian plants used in traditional medicine. J Mycol Méd, 22: 211-216.
72
Sidat MM, Correia D, Buene TP. 2006. Tinea capitis among rural school children of the district of Magude, in Maputo province, Mozambique. Mycoses, 49: 480-483.
73
Singh G, Marimuthu P, de Heluani CS, Catalan C. 2005. Chemical constituents and antimicrobial and antioxidant potentials of essential oil and acetone extract of Nigella sativa seeds. J Sci Food Agric, 85: 2297-2306.
74
Singh SS, Singh DG, Schuff C, de Lampasona MP, Catalán CAN. 2015. Composition, in vitro antioxidant and antimicrobial activities of essential oil and oleoresins obtained from black cumin seeds (Nigella sativa L.). BioMed Res Int, In Press.
75
Sitara U, Niaz I, Naseem J, Sultana N. 2008. Antifungal effect of essential oils on in vitro growth of pathogenic fungi. Pak J Bot, 40: 409-414.
76
Sitheeque MAM, Panagoda GJ, Yau J, Amarakoon AMT, Udagama URN, Samaranayake LP. 2009. Antifungal activity of black tea polyphenols (catechins and thea flavins) against Candida Species. Chemother, 55: 189-196.
77
Staphylakis PK, Gegiou D. 1986. The sterols of Nigella sativa seed oil. Phytochem, 25: 761-763.
78
Sultan MT, Butt MS, Anjum FM, Jamil A, Akhtar S, Nasir M. 2009. Nutritional profile of indigenous cultivar of black cumin seeds and antioxidant potential of its fixed and essential oil. Pak J Bot, 41: 1321-1330.
79
Sunita M, Meenakshi S. 2013. Chemical composition and antidermatophytic activity of Nigella sativa essential oil. Afr J Pharma Pharmacol, 7: 1286-1292.
80
Taha M, Abdel Azeiz AZ, Saudi W. 2010. Antifungal effect of thymol, thymoquinone and thymohydroquinone against yeasts, dermatophytes and non-dermatophyte molds isolated from skin and nails fungal infections. Egypt J Biochem Mol Biol, 28: 109-126.
81
Takruri HRH, Dameh MAF. 1998. Study of nutritional value of black cumin seeds (Nigella sativa L.). J Sci Food Agric, 76: 404-410.
82
Toma CC, Simu GM, Hanganu M, Olah N, Vata FMG, Hammami C, Hammami M. 2010. Chemical composition of the Tunisian Nigella sativa. Note I. Profile on essential oil. Farmacia, 58: 458-464.
83
Uz E, BayraK O, Uz E, Kaya A, Baayrak R. 2008. Nigella sativa oil for prevention of chroniccyclosporine nephrotoxicity: An experimental model. Am J Nephrol, 28: 517-522.
84
Venkatachallam UKT, Pattekhan H, Divakar S, Kadimi US. 2010. Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxide. J Food Sci Technol, 47: 598-605.
85
Yahyaraeyat R, Khosravi AR, Shahbazzadeh D, Khalaj V. 2013. The potential effects of Zataria multiflora Boiss essential oil on growth, aflatoxin production and transcription of aflatoxin biosynthesis pathway genes of toxigenic Aspergillus parasiticus. Braz J Microbiol, 44: 649-655.
86
Yoshinari T, Akiyama T, Nakamura K, Kondo T, Takahashi Y, Muraoka Y, Nonomura Y, Nagasawa H, Sakuda S. 2007. Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus. Microbiol, 153: 2774-2780.
87
Youssef MKE, Eshak NS, Hana RS. 2013. Physicochemical characteristics, nutrient content and fatty acid composition of Nigella sativa oil and sesame oil. Food Pub Health, 3: 309-314.
88
Zaoui A, Cherrah Y, Lacaille-Dubois MA, Settaf A, Amarouch H, Hassar M. 2000. Diuretic and hypotensive effects of Nigella sativa in the spontaneously hypertensive rat. Therapie, 55: 379-382.
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ORIGINAL_ARTICLE
Effects of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress status in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial
Objectives: Nigella sativa is a medicinal plant that has long been used in traditional medicine for treating various conditions. Numerous animal studies provided evidences that the seed may elicit a broad anti-inflammatory/anti-oxidant activity. The aim of the present clinical trial was to evaluate anti-inflammatory and antioxidant properties of Nigella sativa oil in patients with rheumatoid arthritis (RA). Materials and Methods: Forty-two patients with RA were assigned into two groups in this randomized, double blind, placebo-controlled clinical trial. Subjects in intervention group received two capsules, 500 mg each, of Nigella sativa oil, each day for 8 weeks. The other group consumed two capsules as placebo per day for the same period of time. Serum TNF-α, IL-10, and whole blood levels of oxidative stress parameters were measured at baseline and end of the trial. Results: The serum level of IL-10 was increased in the Nigella sativa group (p<0.01). Moreover, treatment with Nigella sativa led to significant reduction of serum MDA and NO compared with baseline (p<0.05). There were no significant differences in the TNF-α, SOD, catalase, and TAS values between or within the groups, before and after the intervention (p>0.05). Conclusions: This study indicates that Nigella sativa could improve inflammation and reduce oxidative stress in patients with RA. It is suggested that Nigella sativa may be a beneficial adjunct therapy in this population of patients
https://ajp.mums.ac.ir/article_3910_70c4f6e446e33f23fb426d1832a9e880.pdf
2016-01-01
34
43
10.22038/ajp.2016.3910
Nigella Sativa
Rheumatoid arthritis
Oxidative stress
IL-10
TNF-α
Vahid
Hadi
vahidhadi1@gmail.com
1
Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Sorayya
Kheirouri
kheirouris@tbzmed. ac.ir
2
Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
LEAD_AUTHOR
Mohammad
Alizadeh
mdalizadeh @ tbzmed .ac . ir
3
Department of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Alireza
Khabbazi
4
Department of Internal Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Hossein
Hosseini
mohosseini @yahoo.com
5
Department of Agriculture, Barij Essence Pharmaceutical Company, Kashan, Iran
AUTHOR
Doyle TJ, Lee JS, Dellaripa PF, Lederer JA, Matteson EL, Fischer A, Ascherman DP, Glassberg MK, Ryu JH, Danoff SK, Brown KK, Collard HR, Rosas IO. 2014. A roadmap to promote clinical and translationalresearch in rheumatoid arthritis-associated interstitial lung disease. Chest, 145: 454-463.
1
Zyrianova Y, Kelly BD, Gallagher C, McCarthy C, Molloy MG, Sheehan J, Dinan TG. 2006. Depression and anxiety in rheumatoid arthritis: the role of perceived social support. Ir J Med Sci, 175: 32-36.
2
Goronzy JJ, Weyand CM. 2009. Developments in the scientific understanding of rheumatoid arthritis. Arthritis Res Ther, 11:249.
3
Weyand CM, Goronzy JJ, Takemura S, Kurtin PJ. 2000. Cell-cell interactions in synovitis. Interactions between T cells and B cells in rheumatoid arthritis. Arthritis Res, 2: 457-463.
4
El Gazzar MA, El Mezayen R, Nicolls MR, Dreskin SC. 2007. Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim Biophys Acta, 1770: 556-564.
5
Yudoh K, Matsuno H, Nakazawa F, Yonezawa T, Kimura T. 2000. Reduced expression of the regulatory CD4+ T cell subset is related to Th1/Th2 balance and disease severity in rheumatoid arthritis. Arthritis Rheum, 43: 617-627.
6
Ebru U, Burak U, Yusuf S, Reyhan B, Arif K, Faruk TH, Emin M, Aydin K, Atilla II, Semsettin S, Kemal E. 2008. Cardioprotective effects of Nigella sativa oil on cyclosporine A-induced cardiotoxicity in rats. Basic Clin Pharmacol Toxicol, 103: 574-580.
7
Wadley AJ, Veldhuijzen van Zanten JJ, Stavropoulos-Kalinoglou A, Metsios GS, Smith JP, Kitas GD, Aldred S.. 2014. Three months of moderate-intensity exercise reduced plasma 3-nitrotyrosine in rheumatoid arthritis patients. Eur J Appl Physiol, 114: 1483-1492.
8
Kurien BT, Scofield RH. 2003. Free radical mediated peroxidative damage in systemic lupus erythematosus. Life Sci, 73: 1655-1666.
9
Amin, G. R. 1991. Popular medicinal plants of Iran, Iranian Research Institute of Medicinal Plants Tehran.
10
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
11
El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, Nikami H, Takewaki T. 2005. Macrophage-derived cytokine and nitric oxide profiles in type I and type II diabetes mellitus: effect of thymoquinone. Acta Diabetol, 42: 23-30.
12
Toubi E, Kessel A, Mahmudov Z, Hallas K, Rozenbaum M, Rosner I. 2005. Increased spontaneous apoptosis of CD4+ CD25+ T cells in patients with active rheumatoid arthritis is reduced by infliximab. Ann N Y Acad Sci, 1051: 506-514.
13
Gheita, T. A. and S. A. Kenawy. 2012. "Effectiveness of Nigella sativa oil in the management of rheumatoid arthritis patients: a placebo controlled study." Phytother Res, 26: 1246-1248.
14
Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A. 1993. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci (Lond), 84: 407-412.
15
Aebi H. 1984. Catalase in vitro. Methods Enzymol, 105: 121-6.
16
Moshage H, Kok B, Huizenga JR, Jansen PL. 1995. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem, 41: 892-896.
17
Bilici M, Efe H, Köroğlu MA, Uydu HA, Bekaroğlu M, Değer O. 2001. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord, 64: 43-51.
18
Katsoulis K, Kontakiotis T, Leonardopoulos I, Kotsovili A, Legakis IN, Patakas D. 2003. Serum total antioxidant status in severe exacerbation of asthma: correlation with the severity of the disease. J Asthma, 40: 847-854.
19
Majdalawieh AF, Hmaidan R, Carr RI. 2010. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol, 131: 268-275.
20
Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. 2012. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact, 197: 40-46.
21
Tekeoglu, I., A. Dogan, L. Ediz, M. Budancamanak and A. Demirel. 2007. "Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models." Phytother Res, 21: 895-897.
22
Schett G, Stach C, Zwerina J, Voll R, Manger B. 2008. How antirheumatic drugs protect joints from damage in rheumatoid arthritis. Arthritis Rheum, 58: 2936-2948.
23
Williams RO. 2004. Collagen-induced arthritis as a model for rheumatoid arthritis. Methods Mol Med, 98: 207-216.
24
Juarranz Y, Abad C, Martinez C, Arranz A, Gutierrez-Canas I, Rosignoli F, Gomariz RP, Leceta J. 2005. Protective effect of vasoactive intestinal peptide on bone destruction in the collagen-induced arthritis model of rheumatoid arthritis. Arthritis Res Ther, 7: R1034-1045.
25
Majdalawieh AF, Carr RI. 2010. In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum). J Med Food, 13: 371-381.
26
Wu CH, Lin MC, Wang HC, Yang MY, Jou MJ, Wang CJ. 2011. Rutin inhibits oleic acid induced lipid accumulation via reducing lipogenesis and oxidative stress in hepatocarcinoma cells. J Food Sci, 76: T65-72.
27
Schulz JB, Lindenau J, Seyfried J, Dichgans J. 2000. Glutathione, oxidative stress and neurodegeneration. Eur J Biochem, 267: 4904-4911.
28
Seo WG, Pae HO, Oh GS, Chai KY, Kwon TO, Yun YG, Kim NY, Chung HT. 2001. Inhibitory effects of methanol extract of Cyperus rotundus rhizomes on nitric oxide and superoxide productions by murine macrophage cell line, RAW 264.7 cells. J Ethnopharmacol, 76: 59-64.
29
Blanco FJ, Ochs RL, Schwarz H, Lotz M. 1995. Chondrocyte apoptosis induced by nitric oxide. Am J Pathol, 146: 75-85.
30
El-Mahmoudy A, Matsuyama H, Borgan MA, Shimizu Y, El-Sayed MG, Minamoto N, Takewaki T. 2002. Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages. Int Immunopharmacol, 2: 1603-1611.
31
Sayed-Ahmed, M. M., A. M. Aleisa, S. S. Al-Rejaie, A. A. Al-Yahya, O. A. Al-Shabanah, M. M. Hafez and M. N. Nagi. 2010. "Thymoquinone attenuates diethylnitrosamine induction of hepatic carcinogenesis through antioxidant signaling." Oxid Med Cell Longev, 3: 254-261.
32
Hassan, A. S., J. H. Ahmed and S. S. Al-Haroon. 2012. A study of the effect of Nigella sativa (Black seeds) in isoniazid (INH)- induced hepatotoxicity in rabbits. Indian J Pharmacol, 44: 678-682
33
Seif, A. A. 2014. "Nigella Sativa reverses osteoporosis in ovariectomized rats."BMC Complement Altern Med, 14: 22.
34
Wilkins R, Tucci M, Benghuzzi H. 2011. Role of plant-derived antioxidants on NF-kb expression in LPS-stimulated macrophages - biomed. Biomed Sci Instrum, 47: 222-227.
35
El Gazzar MA, El Mezayen R, Nicolls MR, Dreskin SC. 2007. Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim Biophys Acta, 1770: 556-564.
36
Ahn K, Aggarwal B. 2005. Transcription Factor NF-κB : A Sensor for Smoke and Stress Signals. Ann N Y Acad Sci, 1056: 218-233.
37
Ishibashi T. 2013. Molecular Hydrogen: New Antioxidant and Anti-inflammatory Therapy for Rheumatoid Arthritis and Related Diseases. Curr Pharm Des, 19: 6375-6381
38
Woo CC, Kumar AP, Sethi G, Tan KH. 2012. Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol, 83: 443-451.
39
ORIGINAL_ARTICLE
The protective effect of Nigella sativa against cisplatin-induced nephrotoxicity in rats
Objective: The clinical use of cisplatin is highly restricted, because of its nephrotoxicity.In this study the protective effect of Nigella sativa (N. sativa) against cisplatin-induced nephrotoxicity was investigated in rats. Materials and Methods: In the current study, the effects of the administration of aqueous-ethanolic extract of N. sativa (100 and 200 mg/kg, BW) and vitamin E (100 mg/kg, BW) against blood and urine biochemical alterations and kidney function in rats treated with cisplatin were investigated. Cisplatin was injected at a dose of 6 mg/kg, BW, on the sixth day of the experiment. Results: The results indicated significant changes in serum urea and creatinine concentration, urine glucose concentration, and urine output in cisplatin group compared with control group. Serum urea and creatinine concentration in preventive and preventive+treatment vitamin E and preventive+treatment N. sativa (200 mg/kg, BW) groups and also serum creatinine concentration in preventive+treatment N. sativa (100 mg/kg, BW) group significantly decreased compared with cisplatin group. Urine glucose concentration in preventive and preventive+treatment N. sativa groups and urine output in preventive and preventive+treatment N. sativa (200 mg/kg, BW) groups significantly decreased compared with cisplatin group.Osmolarity excretion rate in preventive and preventive+treatment vitamin E and preventive N. sativa groups was significantly higher than control group. Conclusions: The current study suggests that N. sativa extract and vitamin E in a dose- and time-dependent manner improved the serum and urine biochemical parameters and kidney function in cisplatin-induced nephrotoxicity in rats. However, it needs more investigations to determine the mechanism of N. sativa action on cisplatin-induced kidney toxicity.
https://ajp.mums.ac.ir/article_4046_42345665e53c01afde657052133f46a3.pdf
2016-01-01
44
54
10.22038/ajp.2016.4046
Cisplatin
Nigella Sativa
Vitamin E
Renal failure
Sara
Hosseinian
hoseinians@mums.ac.ir
1
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Abolfazl
Khajavi rad
khajavirada@mums.ac.ir
2
Neurogenic Inflammation Research Center, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
LEAD_AUTHOR
Mousa-Al-Reza
Hadjzadeh
hajzadehmr@mums.ac.ir
3
Neurocognitive Research Center, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Nema
Mohamadian Roshan
roshann@mums.ac.ir
4
Departmant of Pathology, Qaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Shahrzad
Havakhah
havakhahsh891@mums.ac.ir
5
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Somayeh
Shafiee
shafiees2@mums.ac.ir
6
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Ahmad A, Husain A, Mujeeb M, Alam Khan S, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
1
Ali BH, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. Phytother Res, 17: 299-305.
2
Alimohammadi S, Hobbenaghi R, Javanbakht J, Kheradmand D, Mortezaee R, Tavakoli M, Khadivar F, Akbari H. 2013. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn Pathol, 8: 137.
3
Al-Naqeeb G, Maznah I, Al-Zubairi AS. 2009. Fatty acid profile, α-tocopherol content and total antioxidant activity of oil extracted from Nigella sativa seeds. Int J Pharmacol, 5: 244-250.
4
Antunes LMG, Darin JDC, Bianchi LMP. 2001. Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Rese, 43: 145–150.
5
Arany I, Megyesi JK, Kaneto H, Price PM, Safirstein RL. 2004. Cisplatin-induced cell death is EGFR/src/ERK signaling dependent in mouse proximal tubule cells. Am J Physiol Renal Physiol, 287: F543–F549.
6
Ashraf SS, Rao MV, Kaneez FS, Qadri S, Al-Marzouqi AH, Chandranath IS, Adem A. 2011. Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress.J Chromatogr Sci, 49: 321-326.
7
Badary OA. 1999. Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice. J Ethnopharmacol, 67: 135-42.
8
Badary OA, Nagi MN, Al-Shabanah OA, Al-Sawaf HA, Al-Sohaibani MO, Al-Bekairi AM. 1997. Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol, 75: 1356-1361.
9
Butt MS, Sultan MT. 2010. Nigella sativa: reduces the risk of various maladies. Crit Rev Food Sci Nutr, 50: 654-665.
10
Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA.2009. Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.HBP (Oxford), 11: 373-381.
11
Chirino YI, Pedraza-Chaverri J. 2009. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol, 61: 223-242.
12
Ciarimboli G. 2014. Membrane Transporters as Mediators of Cisplatin Side Effects. Anticancer Res, 34: 547-550.
13
Egawa Takata T, Endo H, Fujita M, Ueda Y, Miyatake T, Okuyama H, Yoshino K, Kamiura S, Enomoto T, Kimura T. 2010. Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer. Cancer Sci, 101: 2171-1278.
14
El Daly ES. 1996. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Islamic Acad Sci , 9: 105-118.
15
Fallah Huseini H, Amini M, Mohtashami R, Ghamarchehre ME, Sadeqhi Z, Kianbakht S, Fallah Huseini A. 2013. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res, 27: 1849-1853.
16
Francescato HD, Coimbra TM, Costa RS, Bianchi Mde L. 2004. Protective effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis. Kidney Blood Press Res, 27: 148-158.
17
Ikari A, Nagatani Y, Tsukimoto M, Harada H, Miwa M, Takagi K. 2005. Sodium-dependent glucose transporter reduces peroxynitrite and cell injury caused by cisplatin in renal tubular epithelial cells.Biochim Biophys Acta, 1717: 109-117.
18
Ito Y, Arahata Y, Goto Y, Hirayama M, Nagamutsu M, Yasuda T, Yanagi T, Sobue G.1998. Cisplatin neurotoxicity presenting as reversible posterior leukoencephalopathy syndrome. Am J Neuroradiol, 19: 415.
19
Katzung BG. 2004. Basic and Clinical Pharmacology. pp. 906, NewYork: McGraw-Hill.
20
Kawai Y, Nakao T, Kunimura N,Kohda Y, Gemba M. 2006. Relationship of intracellular calcium and oxygen radicals to Cisplatin-related renal cell injury. J PharmacolSci, 100: 65–72.
21
Khan A, Chen HC, Tania M, Zhang DZ. 2011.Anticancer Activities of Nigella sativa (Black Cumin). Afr J Tradit Complement Altern Med, 8: 226-232.
22
Kim SW, Lee JU, Nah MY, Kang DG, Ahn KY, Lee HS, Choi KC. 2001. Cisplatin decreases the abundance of aquaporin water channels in rat kidney. J Am Soc Nephrol,12: 875-882.
23
Kim YH, Kim YW, Oh YJ, Back N, Chung SA, Chung HG, Jeong TS, Choi MS, Lee KT. 2006. Protective effect of the ethanol extract of the roots of Brassica rapa on cisplatin-induced nephrotoxicity in LLC-PK1 cells and rats. Biol Pharm Bull, 29: 2436-2441.
24
Kim YK, Byun HS, Kim YH, Woo JS, Lee SH. 1995. Effect of cisplatin on renal function in rabbits:mechanism of reduced glucose reabsorption. Toxicol Appl Pharmacol, 130: 19-26.
25
Kishore BK, Krane CM, Di Iulio D, Menon AG, Cacini W. 2000. Expression of renal aquaporins 1, 2, and 3 in a rat model of cisplatin-induced polyuria. Kidney Int, 58: 701-711.
26
Kroning R, Lichtenstein AK, Nagami GT. 2000. Sulfur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines. Cancer Chemother Pharmacol, 45: 43–49.
27
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. 2010. Mechanisms of Cisplatin Nephrotoxicity.Toxins, 2: 2490-2518.
28
Morsi NM. 2000. Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Microbiol Pol. 49: 63-74.
29
Naghizadeh B, Boroushaki MT, Vahdati Mashhadian N, Mansouri SMT. 2008. Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. Iran Biomed J, 12: 93-100.
30
Nath KA, Norby SM. 2000. Reactive oxygen species and acute renal failure. Am J Med, 109: 665-678.
31
Portilla D, Li S, Nagothu K, Megyesi J, Kaissling B, Schnackenberg L, Safirstein RL, Beger RD. 2006. Metabolomic study of cisplatin-induced nephrotoxicity. Kidney Int, 69: 2194-2204.
32
Ramesh G, Reeves WB. 2004. Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha. Kidney Int , 65: 490–499.
33
Randhawa MA. 2008. Black seed, Nigella sativa, deserves more attention. J Ayub Med Coll Abbottabad, 20: 1-2.
34
Razzaque MS. 2007. Cisplatin nephropathy: is cytotoxicity avoidable? Nephrol Dial Transplant, 22: 2112-2116.
35
Rooney S and Ryan MF. 2005. Effects of Alpha-hederin and Thymoquinone, constituents of Nigella sativa, on Human Cancer Cell Lines. Anticancer Res, 25: 2199-2204.
36
Salama RHM, Abd-El-Hameed NA, Abd-El-Ghaffar SKH, Mohammed ZT, Ghandour NMA. 2011. Nephroprotective Effect of Nigella sativa and Matricaria chamomilla in Cisplatin Induced Renal Injury. Int J Clin Med, 2: 185-195.
37
Salem ML. 2005. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int J Immunopharmacol, 5: 1749-1770.
38
Shimeda Y, Hirotani Y, Akimoto Y, Shindou K, Ijiri Y, Nishihori T, Tanaka K. 2005. Protective Effects of Capsaicin against Cisplatin-Induced Nephrotoxicity in Rats. Biol Pharm Bull, 28: 1635-1638.
39
Tikoo K, Bhatt DK, Gaikwad AB, Sharma V, Kabra DG.2007.Differential effects of tannic acid on cisplatin induced nephrotoxicity in rats. FEBS Lett, 581: 2027-2035.
40
Wong NL, Walker VR, Wong EF, Sutton RA.1993. Mechanism of polyuria after cisplatin therapy.Nephron, 65: 623-627.
41
Yaman I, Balikci E. 2010. Protective effects of Nigella sativa against gentamicin-induced nephrotoxicity in rats. Exp Toxicol Pathol, 62: 183-19
42
Yao X, Panichpisal K, Kurtzman N, Nugent K. 2007. Cisplatin nephrotoxicity: a review. Am J Med Sci, 334: 115-124.
43
ORIGINAL_ARTICLE
Attenuation of morphine tolerance and dependence by thymoquinone in mice
Objectives: Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice. Materials and Methods: Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively) during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p.) was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination. Results: Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p.) significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days) and also single injection of thymoquinone (40 mg/kg, on the fourth day) attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg) produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg). Conclusion: Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine.
https://ajp.mums.ac.ir/article_4402_919389c7b4720d86a89ad8639dd23cc0.pdf
2016-01-01
55
66
10.22038/ajp.2016.4402
Thymoquinone
Nigella Sativa
Morphine
Dependence
Tolerance
Pain
Hossein
Hosseinzadeh
hosseinzadehh@mums.ac.ir
1
Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Siavash
Parvardeh
parvardehs@sbmu.ac.ir
2
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
LEAD_AUTHOR
Alireza
Masoudi
dr.masoudi90@yahoo.com
3
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
AUTHOR
Mahsa
Moghimi
mahsa_764314@yahoo.com
4
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
AUTHOR
Fatemeh
Mahboobifard
amirshayan7@gmail.com
5
Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
AUTHOR
Abdel-Fattah AM, Matsumoto K, Watanabe H. 2000. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol, 400: 89-97.
1
Abdel-Zaher AO, Abdel-Rahman MS, ELwasei FM. 2010. Blockade of nitric oxide overproduction and oxidative stress by Nigella sativa oil attenuates morphine-induced tolerance and dependence in mice. Neurochem Res, 35: 1557-1565.
2
Abdel-Zaher AO, Abdel-Rahman MS, ELwasei FM. 2011. Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: Role of nitric oxide and oxidative stress. Neurotoxicology, 32: 725-733.
3
Abdel-Zaher AO, Mostafa MG, Farghaly HSM, Hamdy MM, Abdel-Hady RH. 2013. Role of oxidative stress and inducible nitric oxide synthase in morphine-induced tolerance and dependence in mice. Effect of alpha-lipoic acid. Behav Brain Res, 247: 17-26.
4
Ahmad A, Husain A, Mujeeb M, Alam Khan S, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
5
Akhondian J, Kianifar H, Raoofziaee M, Moayedpour A, Toosi MB, Khajedaluee M. 2011. The effect of thymoquinone on intractable pediatric seizures (pilot study). Epilepsy Res, 93: 39-43.
6
Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA, Williams BR. 2013. Koda-Kimble and Young’s applied therapeutics: the clinical use of drugs, pp. 112-146, Philadelphia, Lippincott Williams & Wilkins.
7
Al-Sheddi ES, Farshori NN, Al-Oqail MM, Musarrat J, Al-Khedhairy AA, Siddiqui MA. 2014. Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer cell line. Asian Pac J Cancer Prev, 15: 983-987.
8
Babazadeh B, Sadeghnia HR, Safarpour Kapurchal E, Parsaee H, Nasri S, Tayarani-Najaran Z. 2012. Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells. Avicenna J Phytomed, 2: 125-132.
9
Bashir MU, Qureshi HJ. 2010. Analgesic effect of Nigella sativa seeds extract on experimentally induced pain in albino mice. J Coll Physicians Surg Pak, 20: 464-467.
10
Bhandari PR. 2014. Potential role of Nigella sativa (black cumin) in epilepsy. Int J Nutr Pharmacol Neurol Dis, 4: 188.
11
Boskabady MH, Keyhanmanesh R, Khamneh S, Ebrahimi MA. 2011. The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs. Clinics, 66: 879-887.
12
Boskabady MH, Kiani S, Jandaghi P. 2004. Stimulatory effect of Nigella sativa on b2-adrenoceptors of guinea pig tracheal chains. MJIRI, 18: 153-158.
13
Boskabady MH, Mohsenpoor N, Takaloo L. 2010. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine, 17: 707-713.
14
Bourgou S, Pichette A, Marzouk B, Legault J. 2012. Antioxidant, anti‐inflammatory, anticancer and antibacterial activities of extracts from Nigella sativa (black cumin) plant parts. J Food Biochem, 36: 539-546.
15
Cikman O, Ozkan A, Aras AB, Soylemez O, Alkis H, Taysi S, et al. 2014. Radioprotective effects of Nigella sativa oil against oxidative stress in liver tissue of rats exposed to total head irradiation. J Invest Surg, 27: 262-266.
16
Contet C, Kieffer BL, Befort K. 2004. Mu opioid receptor: a gateway to drug addiction. Curr Opin Neurobiol, 14: 370-378.
17
Develi S, Evran B, Betül Kalaz E, Koçak-Toker N, Erata GÖ. 2014. Protective effect of Nigella sativa oil against binge ethanol-induced oxidative stress and liver injury in rats. Chin J Nat Med, 12: 495-499.
18
Dogrul A, Zagli U, Tulunay FC. 2002. The role of T-type calcium channels in morphine analgesia, development of antinociceptive tolerance and dependence to morphine, and morphine abstinence syndrome. Life Sci, 71: 725-734.
19
Dollah MA, Parhizkar S, Izwan M. 2013. Effect of Nigella sativa on the kidney function in rats. Avicenna J Phytomed, 3: 152-158.
20
Doyle T, Bryant L, Batinic-Haberle I, Little J, Cuzzocrea S, Masini E, Spasojevic I, Salvemini D. 2009. Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance. Neuroscience, 164: 702-710.
21
Ezz HSA, Khadrawy YA, Noor NA. 2011. The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: a comparison with valproate. Neurochem Res, 36: 2195-2204.
22
Gilhotra N, Dhingra D. 2011. Thymoquinone produced antianxiety-like effects in mice through modulation of GABA and NO levels. Pharmacol Rep, 63: 660-669.
23
Han Y, Jiang C, Tang J, Wang C, Wu P, Zhang G, Liu W, Jamangulova N, Wu X, Song X. 2014. Resveratrol reduces morphine tolerance by inhibiting microglial activation via AMPK signalling. Eur J Pain, doi: 10.1002/ejp.511.
24
Hobbenaghi R, Javanbakht J, Sadeghzadeh S, Kheradmand D, Abdi FS, Jaberi MH, et al. 2014. Neuroprotective effects of Nigella sativa extract on cell death in hippocampal neurons following experimental global cerebral ischemia-reperfusion injury in rats. J Neurol Sci, 337: 74-79.
25
Hosseinzadeh H, Fazly Bazzaz BS, Haghi MM. 2007. Antibacterial activity of total extracts and essential oil of Nigella sativa L. seeds in mice. Pharmacologyonline, 2: 429-435.
26
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. 2007. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine, 14: 621-7.
27
Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri MT. 2005. Intra-cerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monitor, 11: 106-110.
28
Hosseinzadeh H, Parvardeh S. 2004. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine, 11: 56-64.
29
Imenshahidi M, Hosseinzadeh H, Es'haghian A. 2007. Effects of ethosuximide on morphine tolerance and dependence in mice. Pharmacologyonline, 2: 287-299.
30
Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, Azmi NH, Ghafar SA, Chan KW. 2013. Thymoquinone prevents β-amyloid neurotoxicity in primary cultured cerebellar granule neurons. Cell Mol Neurobiol, 33: 1159-1169.
31
Jrah-Harzallah H, Ben-Hadj-Khalifa S, Almawi WY, Maaloul A, Houas Z, Mahjoub T. 2013. Effect of thymoquinone on 1, 2-dimethyl-hydrazine-induced oxidative stress during initiation and promotion of colon carcinogenesis. Eur J Cancer, 49: 1127-1135.
32
Jrah-Harzallah H, Grayaa R, Kharoubi W, Maaloul A, Hammami M, Mahjoub T. 2012. Thymoquinone, the Nigella sativa bioactive compound, prevents circulatory oxidative stress caused by 1, 2-dimethylhydrazine in erythrocyte during colon post-initiation carcinogenesis. Oxid Med Cell Longevity, 2012.
33
Khan A, Vaibhav K, Javed H, Khan MM, Tabassum R, Ahmed ME. 2012. Attenuation of Aβ-induced neurotoxicity by thymoquinone via inhibition of mitochondrial dysfunction and oxidative stress. Mol Cell Biochem, 369: 55-65.
34
Leong XF, Rais Mustafa M, Jaarin K. 2013. Nigella sativa and its protective role in oxidative stress and hypertension. Evid Based Complement Altern Med, 2013. Doi: 10.1155/2013/120732.
35
Mansouri MT, Naghizadeh B, Ghorbanzadeh B. 2014. Ellagic acid enhances morphine analgesia and attenuates the development of morphine tolerance and dependence in mice. Eur J Pharmacol, 741: 272-280.
36
Mathur ML, Gaur J, Sharma R, Haldiya KR. 2011. Antidiabetic properties of a spice plant Nigella sativa. J Endocrinol Metab, 1: 1-8.
37
Norfazlina MN, Farida Zuraina MY, Rajab NF, Mohd Nazip S, Rumiza AR, Suziana Zaila CF. 2014. In vitro cytotoxicity effects of single and combination Nigella sativa and Zingiber zerumbet extracts on human myeloid leukemia (HL60) cells and its mode of cell death. J Appl Pharm Sci, 4: 51-55.
38
Özek M, Üresin Y, Güngör M. 2003. Comparison of the effects of specific and nonspecific inhibition of nitric oxide synthase on morphine analgesia, tolerance and dependence in mice. Life Sci, 72: 1943-1951.
39
Park HS, Lee HY, Kim YH, Park JK, Zvartau EE, Lee H. 2006. A highly selective k-opioid receptor agonist with low addictive potential and dependence liability. Bioorg Med Chem Lett, 16: 3609-3613.
40
Parvardeh S, Fatehi M. 2003. Effects of thymoquinone, the major constituent of Nigella sativa seeds, on the contractile response of rat vas deferens. Pharmac Biol, 41: 616-621.
41
Parvardeh S, Fatehi M. 2007. Inhibitory effects of thymoquinone, the major component of Nigella sativa seeds, on spontaneous and evoked contractions of guinea pig isolated ileum. J Med Plants, 6: 25-35.
42
Pasternak GW. 2001. Insights into mu opioid pharmacology; the role of mu opioid receptor subtypes. Life Sci, 68: 2213-2219.
43
Radad K, Hassanein K, Al-Shraim M, Moldzio R, Rausch WD. 2014. Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats. Exp Toxicol Pathol, 66: 13-17.
44
Sayed AA. 2012. Thymoquinone and proanthocyanidin attenuation of diabetic nephropathy in rats. Eur Rev Med Pharmacol Sci, 16: 808-815.
45
Seth V, Upadhyaya P, Moghe V, Ahmad M. 2011. Role of calcium in morphine dependence and naloxone-precipitated withdrawal in mice. J Exp Pharmacol, 3: 7-12.
46
Shimatani T, Adachi H, Mihashi H, Usumoto N, Yoshimoto K, Ayukawa K. 2014. Calcium channel blocker attenuated opioid withdrawal syndrome. Acute Med Surg, DOI: 10.1002/ams2.72.
47
Shippenberg TS, Zapata A, Chefer VI. 2007. Dynorphin and the pathophysiology of drug addiction. Pharmacol Ther, 116: 306-321.
48
Sultan MT, Butt MS, Karim R, Iqbal SZ, Ahmad S, Zia-Ul-Haq M, Aliberti L, Ahmad AN, De Feo V. 2014. Effect of Nigella sativa fixed and essential oils on antioxidant status, hepatic enzymes, and immunity in streptozotocin induced diabetes mellitus. BMC Complement Altern Med, 14: 193.
49
Sultan MT, Butt MS, Karim R, Zia-Ul-Haq M, Batool R, Ahmad S, Aliberti L, De Feo V. 2014. Nigella sativa fixed and essential oil supplementation modulates hyperglycemia and allied complications in streptozotocin-induced diabetes mellitus. Evid Based Complement Alternat Med, 2014: 826380. doi: 10.1155/2014/826380.
50
Suzuki T, Tsuda M, Narita M, Funada M, Mizoguchi H, Misawa M. 1996. Diazepam pretreatment suppresses morphine withdrawal signs in the mouse. Life Sci, 58: 349-357.
51
Tabatabai SM, Dashti S, Doosti F, Hosseinzadeh H. 2014. Phytotherapy of opioid dependence and withdrawal syndrome: a review. Phytother Res, 28: 811-830.
52
Tao YM, Li QL, Zhang CF, Xu XJ, Chen J, Ju YW, Chi ZQ, Long YQ, Liu JG. 2008. LPK-26, a novel k-opioid receptor agonist with potent antinociceptive effects and low dependence potential. Eur J Pharmacol, 584: 306-311.
53
Tejwani GA, Rattan AK, Sribanditmongkol P, Sheu M-J, Zuniga J, McDonald JS. 1993. Inhibition of morphine-induced tolerance and dependence by a benzodiazepine receptor agonist midazolam in the rat. Anesth Analg, 76: 1052-1060.
54
Tejwani GA, Sheu M-J, Sribanditmongkol P, Satyapriya A. 1998. Inhibition of morphine tolerance and dependence by diazepam and its relation to m-opioid receptors in the rat
55
brain and spinal cord. Brain Res, 797: 305-312.
56
Tembhurne SV, Feroz S, More BH, Sakarkar DM. 2014. A review on therapeutic potential of Nigella sativa (kalonji) seeds. J Med Plants Res, 8: 167-177.
57
Tsuji M, Takeda H, Matsumiya T, Nagase H, Yamazaki M, Narita M, Suzuki T. 2000. A novel k-opioid receptor agonist, TRK-820, blocks the development of physical dependence on morphine in mice. Life Sci, 66: 353-358.
58
Vogel HG. 2008. Drug Discovery and Evaluation: Pharmacological Assays, pp. 1013-1014, Berlin, Springer.
59
Zarrindast MR, Mousa-Ahmadi E. 1999. Effects of GABAergic system on naloxone-induced jumping in morphine-dependent mice. Eur J Pharmacol, 381: 129-133.
60
Zarrindast MR, Torkaman-Boutorabi A. 2003. Effects of imipramine on the expression and development of morphine dependence in mice. Eur J Pharmacol, 473: 19-25.
61
Ziaee T, Moharreri N, Hosseinzadeh H. 2012. Review of pharmacological and toxicological effects of Nigella sativa and its active constituents. J Med Plants, 11: 16-42.
62
ORIGINAL_ARTICLE
Nigella sativa seed decreases endothelial dysfunction in streptozotocin-induced diabetic rat aorta
Objective: Diabetes is an important risk factor for cardiovascular events. The great percent of morbidity in patients with diabetes is due to endothelial dysfunction. The present study investigated the effects of hydroalcholic extract of Nigella sativa (N. sativa) on contractile and dilatation response of isolated aorta in streptozotocin (STZ)-induced diabetic rat. Materials and Methods: Rats were divided into six experimental groups (control, untreated STZ-diabetic, and N. sativa hydroalcholic extract or metformin-treated diabetic rats). Treated rats received N. sativa extract (100, 200, and 400 mg/kg) or metformin (300 mg/kg) by gavage, daily for 6 weeks. Isolated rat thoracic rings were mounted in an organ bath system then contractile and dilatation responses induced by phenylephrine (PE), acetylcholine (ACh), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations. Results: The lower concentrations of N. sativa seed extract (DE 100 and DE 200) and metformin significantly reduced the contractile responses to higher concentrations of PE (10-6 - 10-5 M) compared to diabetic group (pThe relaxation response to Ach 10-8M, was increased in DE 200 and metformin groups compared to diabetic group (p<0.05). The relaxation responses to Ach 10-7 - 10-5Mwere significantly higher in all treated groups compared to diabetic group (pConclusion: Chronic administration of N. sativa seed extract has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats.
https://ajp.mums.ac.ir/article_4187_31003b0cd75a46747be9f1d5e5b35f62.pdf
2016-01-01
67
76
10.22038/ajp.2016.4187
Diabetes Mellitus
Nigella Sativa
Endothelial dysfunction
Isolated aorta
Rat
Abbasali
Abbasnezhad
abbasnezhada891@mums.ac.ir
1
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Saeed
Niazmand
niazmands@mums.ac.ir
2
Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Maryam
Mahmoudabady
mahmoudabadym@mums.ac.ir
3
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammad
Soukhtanloo
asadasd@mums.ac.ir
4
Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Seyed Abdolrahim
Rezaee
5
Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Seyed Mojtaba
Mousavi
6
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Abebe W, Harris KH, Macleod KM. 1990. Enhanced contractile responses of arteries from diabetic rats to alpha 1-adrenoceptor stimulation in the absence and presence of extracellular calcium. J Cardiovasc Pharmacol, 16: 239-248.
1
Ahmad A, HusainA, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F, Kishore K. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
2
Ahmad S, Beg ZH. 2013. Elucidation of mechanisms of actions of thymoquinone-enriched methanolic and volatile oil extracts from Nigella sativa against cardiovascular risk parameters in experimental hyperlipidemia. Lipids Health Dis, 12: 86.
3
Calvert JW, Gundewar S, Jha S, Greer JJ, Bestermann WH, Tian R, Lefer DJ. 2008. Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling. Diabetes, 57: 696-705.
4
Capellini VK, Baldo CF, Celotto AC, Batalhao ME, Carnio EC, Rodrigues AJ, Evora PR. 2010. Oxidative stress is not associated with vascular dysfunction in a model of alloxan-induced diabetic rats. Arq Bras Endocrinol Metabol, 54: 530-539.
5
Csanyi G, Lepran I, Flesch T, Telegdy G, Szabo G, Mezei Z. 2007. Lack of endothelium-derived hyperpolarizing factor (EDHF) up-regulation in endothelial dysfunction in aorta in diabetic rats. Pharmacol Rep, 59: 447-455.
6
De Vriese AS, Verbeuren TJ, Van De Voorde J, Lameire NH, Vanhoutte PM. 2000. Endothelial dysfunction in diabetes. Br J Pharmacol, 130: 963-974.
7
Dehkordi FR, Kamkhah AF. 2008. Antihypertensive effect of N. sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol, 22: 447-452.
8
El-Remessy AB, Tawfik HE, Matragoon S, Pillai B Caldwell RB, Caldwell RW. 2010. Peroxynitrite mediates diabetes-induced endothelial dysfunction: possible role of Rho kinase activation. Exp Diabetes Res, 2010: 247861.
9
El-SalehSC, Al-Sagair OA, Al-Khalaf MI. 2004. Thymoquinone and Nigella sativa oil protection against methionine-induced hyperhomocysteinemia in rats. Int J Cardiol, 93: 19-23.
10
Elcioglu KH, Kabasakal L, Cetinel S, Conturk G, Sezen SF, Ayanoglu-Dulger G. 2010. Changes in caveolin-1 expression and vasoreactivity in the aorta and corpus cavernosum of fructose and streptozotocin-induced diabetic rats. Eur J Pharmacol, 642: 113-120.
11
Fallah Huseini H, Amini M, Mohtashami R, Ghamarchehre ME, Sadeqhi Z, Kianbakht S, Fallah Huseini A. 2013. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res, 27: 1849-1853.
12
Ghosheh OA, Houdi AA, Crooks PA. 1999. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed Anal, 19: 757-762.
13
Hartge MM, Unger T, KintscherU. 2007. The endothelium and vascular inflammation in diabetes. Diab Vasc Dis Res, 4: 84-88.
14
Ismail M, Al-Naqeep G, Chan KW. 2010. Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats. Free Radic Biol Med, 48: 664-672.
15
Kaleem M, Kirmani D, Asif M, Ahmed Q, Bano B. 2006. Biochemical effects of Nigella sativa L seeds in diabetic rats. Indian J Exp Biol, 44: 745-748.
16
Katakam PV, Ujhelyi MR, Hoenig M, Miller AW. 2000. Metformin improves vascular function in insulin-resistant rats. Hypertension, 35: 108-112.
17
Kizub IV, Pavlova OO, Johnson CD, Soloviev AI, Zholos AV. 2010. Rho kinase and protein kinase C involvement in vascular smooth muscle myofilament calcium sensitization in arteries from diabetic rats. Br J Pharmacol, 159: 1724-1731.
18
Leong XF, Rais Mustafa M, Jaarin K. 2013. Nigella sativa and Its Protective Role in Oxidative Stress and Hypertension. Evid Based Complement Alternat Med, 2013: 120732.
19
Liu Y, Huang C, Ceng C, Zhan H, Zheng D, Han W. 2014. Metformin enhances nitric oxide production and diminishes Rho kinase activity in rats with hyperlipidemia. Lipids Health Dis, 13: 115.
20
Luscher TF, Creager MA, Beckman JA, Cosentino F. 2003. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part II. Circulation, 108: 1655-1661.
21
Majithiya JB, Balaraman R. 2006. Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats. Life sciences, 78: 2615-2624.
22
Mccarron JG, Bradley KN, Macmillan D, Muir TC. 2003. Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle. Biochem Soc Trans, 31: 920-924.
23
Nergiz C, Otles S. 1993. Chemical composition of Nigella sativa L. seeds. Food Chemistry, 48: 259-261.
24
Niazmand S, Fereidouni E, Mahmoudabady M, Mousavi SM. 2014. Endothelium-independent vasorelaxant effects of hydroalcoholic extract from Nigella sativa seed in rat aorta: the roles of Ca2+ and K+ channels. Biomed Res Int, 2014: 247054.
25
Oyama Y, Kawasaki H, Hattori Y, Kanno M. 1986. Attenuation of endothelium-dependent relaxation in aorta from diabetic rats. Eur J Pharmacol, 132: 75-78.
26
Paneni F, Beckman JA, Creager MA, Cosentino F. 2013. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J, 34: 2436-2443.
27
Pinho JF, Medeiros, MA, Capettini LS, Rezende BA, Campos PP, Andrade SP, Cortes SF, Cruz JS, Lemos VS. 2010. Phosphatidylinositol 3-kinase-delta up-regulates L-type Ca2+ currents and increases vascular contractility in a mouse model of type 1 diabetes. Br J Pharmacol, 161: 1458-1471.
28
Potenza MA, Gagliardi S, Nacci C, Carratu MR, Montagnani M. 2009. Endothelial dysfunction in diabetes: from mechanisms to therapeutic targets. Curr Med Chem, 16: 94-112.
29
Sartoretto JL, Melo GA, Carvalho MH, Nigro D, Passaglia RT, Scavone C, Cuman RK, Fortes ZB. 2005. Metformin treatment restores the altered microvascular reactivity in neonatal streptozotocin-induced diabetic rats increasing NOS activity, but not NOS expression. Life Sci, 77: 2676-2689.
30
Sena CM, Matafome P, Louro T, Nunes E, Fernandes R, Seica RM. 2011. Metformin restores endothelial function in aorta of diabetic rats. Br J Pharmacol, 163: 424-437.
31
Tabit CE, Chung WB, Hamburg NM, Vita JA. 2010. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications. Reviews in Endocrine and Metabolic Disorders, 11: 61-74.
32
Thorneloe KS, Nelson MT. 2005. Ion channels in smooth muscle: regulators of intracellular calcium and contractility. Can J Physiol Pharmacol, 83: 215-242.
33
Xu J, Zou MH. 2009. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation Circulation, 120: 1266-86
34
Zhang LN, Vincelette J, Chen D, Gless RD, Anandan SK, Rubanyi GM, Webb HK, Macintyre DE, Wang YX. 2011. Inhibition of soluble epoxide hydrolase attenuates endothelial dysfunction in animal models of diabetes, obesity and hypertension. Eur J Pharmacol, 654: 68-74.
35
Zou MH, Cohen R, Ullrich V. 2004. Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium, 11: 89-97.
36
ORIGINAL_ARTICLE
Effect of Alpha-Hederin, the active constituent of Nigella sativa, on miRNA-126, IL-13 mRNA levels and inflammation of lungs in ovalbumin-sensitized male rats
Objectives: In previous studies the therapeutic effects of Nigella sativa have been demonstrated on asthmatic animals. In the present study, the preventive effect of single dose of alpha-hederin, its active constituent, has been evaluated on lung inflammation and some inflammatory mediators in lungs of ovalbumin sensitized rat in order to elicit its mechanism. Materials and methods: Forty rats were randomly grouped in 4 groups; control (C), sensitized (S), sensitized pretreated groups with thymoquinone (3 mg/kg i.p., S+TQ) and alpha-hederin (0.02 mg/kg i.p., S+AH). Levels of IL-13 mRNA and miRNA-126 in lung tissue and its pathological changes in each group were assessed. Results: Elevated levels of miRNA-126, IL-13 mRNA and pathological changes were observed in the sensitized group compared to the control group (pConclusion: The results suggested that alpha-hederin had preventive effect on sensitized rats like thymoquinone. It may intervene in miRNA-126 expression, which consequently could interfere with IL-13 secretion pathway leading to a reduction in inflammatory responses.
https://ajp.mums.ac.ir/article_4622_eb1e17b7fc41beaaceda6589f909135c.pdf
2016-01-01
77
85
10.22038/ajp.2016.4622
Alpha-hederin
MiRNA-126
IL-13 mRNA
Ovalbumin
Thymoquinone
Asthma
Maryam
Fallahi
m.fallahi.h@gmail.com
1
Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Rana
Keyhanmanesh
rkeyhanmanesh@gmail.com
2
Medical Education Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Amir Mahdi
Khamaneh
r_keyhanmanesh@yahoo.com
3
Department of molecular medicine, School of advanced medical sciences, Tabriz University of Medical Sciences, Tabriz, Iran
AUTHOR
Mohammad Ali
Ebrahimi Saadatlou
anatomist2001@gmail.com
4
Department of basic sciences, College of veterinary medicine, Tabriz branch, Islamic Azad University, Tabriz, Iran
AUTHOR
Saeideh
Saadat
saadat_1987@yahoo.com
5
Department of Physiology, Faculty of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
AUTHOR
Hadi
Ebrahimi
ehadi2@yahoo.com
6
Tuberculosis and lung diseases research center, Tabriz University of Medical Sciences, Tabriz, Iran
LEAD_AUTHOR
Abd El Aziz AE, El Sayed NS, Mahran LG. 2011. Anti-asthmatic and anti-allergic effects of thymoquinone on airway-induced hypersensitivity in experimental animals. J Appl Pharm Sci, 1: 109-117.
1
Alipour MR, Khamaneh AM, Yousefzadeh N, Mohammad-nejad D, Soufi FG. 2013. Upregulation of microRNA-146a was not accompanied by downregulation of pro-inflammatory markers in diabetic kidney. Mol Biol Rep, 40: 6477-6483.
2
Al-JawadFH, Al-Razzuqi RAM, Hashim HM, Ismael AH. 2012. Broncho-relaxant activity of Nigella sativa versus anthemisnobilis in chronic bronchial asthma; a comparative study of efficacy. IOSR J Pharmac, 2: 81-83.
3
Angulo M, Lecuona E, Sznajder JI. 2012. Role of MicroRNAs in lung disease. Archivos de Bronconeumología (English Edition), 48: 325-330.
4
Barnes PJ. 2001. Th2 cytokines and asthma: an introduction. Respir Res, 2: 64-65.
5
Boskabady MH, Aslani MR. 2005. Possible relaxant effects of thymoquinone on guinea pig tracheal chains. Iran Biomed J, 9: 123-128.
6
Boskabady MH, Mohsenpoor N, Takaloo L. 2010. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine, 17: 707-713.
7
Bosnjak B, Stelzmueller B, Erb KJ, Epstein MM. 2011. Treatment of allergic asthma: modulation of Th2 cells and their responses. Respir Res, 12: 114.
8
Collison A, Herbert C, Siegle, J. Mattes, P. S. Foster and R. K. Kumar. 2011b. Altered expression of microRNA in the airway wall in chronic asthma: miR-126 as a potential therapeutic target. BMC pulmonary medicine, 11: 29.
9
Collison A, Mattes J, Plank M, Foster PS. 2011a. Inhibition of house dust mite–induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy Clin Immunol, 128: 160-167. e4.
10
Gepdiremen A, Mshvildadze V, Süleyman H, Elias R. 2005. Acute anti-inflammatory activity of four saponins isolated from ivy: alpha-hederin, hederasaponin-C, hederacolchiside-E and hederacolchiside-F in carrageenan-induced rat paw edema. Phytomedicine, 12: 440-444.
11
Greene CM, Gaughan KP. 2013. microRNAs in asthma: potential therapeutic targets. Curr Opin Pulm Med, 19:66–72.
12
Grünig G, Corry DB, Reibman J, Wills-Karp M. 2012. Interleukin 13 and the evolution of asthma therapy. Am J Clin Exp Immunol, 1: 20.
13
Hocaoglu AB, Karaman O, Erge DO, Erbil G, Yilmaz O, Kivcak B, Bagriyanik A, Uzuner N. 2012. Effect of hedera helix on lung histopathology in chronic asthma. Iran J Allergy, Asthma Immunol, 11: 316-323.
14
Hosseinzadeh H, Eskandari M, Ziaee T. 2008. Antitussive effect of thymoquinone, a constituent of Nigella sativa seeds, in guinea pigs. Pharmacologyonline, 2: 480-484.
15
Keyhanmanesh R, Boskabady MH, Khamneh S, Doostar Y. 2010. Effect of thymoquinone on the lung pathology and cytokine levels of ovalbumin-sensitized guinea pigs. Pharmacol rep, 62: 910-916.
16
Keyhanmanesh R, Gholamnezhad Z, Boskabady MH. 2014b. The relaxant effect of Nigella sativa on smooth muscles, its possible mechanisms and clinical applications. Iran J Basic Med Sci, 17: 939-949.
17
Keyhanmanesh R, Pejman L, Omrani H, Mirzamohammadi Z, Shahbazfar AA. 2014a. The effect of single dose of thymoquinone, the main constituents of Nigella sativa, in guinea pig model of asthma. BioImpacts, 4: 75.
18
Kumar M, Ahmad T, Sharma A, Mabalirajan U, Kulshreshtha A, Agrawal A, et al. 2011. Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol,128:1077–1085.
19
Mattes J, Collison A, Plank M, Phipps S, Foster PS. 2009. Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease. Proc Nat Acad Sci, 106: 18704-18709.
20
May R, Monk P, Cohen E, Manuel D, Dempsey F, Davis N, Dodd A, Corkill D, Woods J, Joberty-Candotti C, Conroy L, Koentgen F, Martin E, Wilson R, Brennan N, Powell J, Anderson I. 2011. Preclinical development of CAT-354, an IL-13-neutralising antibody, for the treatment of severe uncontrolled asthma. Br J Pharmacol, 166: 177-93.
21
Oglesby IK, Mc Elvaney NG, Greene CM. 2010. MicroRNAs in inflammatory lung disease-master regulators or target practice? Respiratory research, 11: 148.
22
Rad MK, Neamati A, Boskabady MH, Mahdavi-Shahri N, Mahmoudabady M. 2012. The preventive effect of Brassica napus L. oil on pathophysiological changes of respiratory system in experimental asthmatic rat.Avicenna J
23
Phytomed, 3: 56-63.
24
Rooney S, Ryan M. 2005. Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Anticancer res, 25: 4255-4259.
25
Saadat S, Mohammadi M, Fallahi M, keyhanmanesh R, Aslani MR. 2015.The protective effect of α-hederin, the active constituent of Nigella sativa, on tracheal responsiveness and lung inflammation in ovalbumin sensitized guinea pigs. J Physiol Sci, 65: 285-92.
26
Tsitsiou E, Williams AE, Moschos SA, Patel K, Rossios C, Jiang, X, Adams O, Macedo P, Booton R, Gibeon D, Chung KF, Lindsay MA. 2012. Transcriptome analysis shows activation of circulatingCD81 T cells in patients with severe asthma. American Academy of Allergy, Asthma Immunol, 129(1): 96-103.
27
Wolf A, Gosens R , Meurs H, Häberlein H. 2011. Pre-treatment with α-hederin increases β-adrenoceptor mediated relaxation of airway smooth muscle. Phytomedicine, 18: 214-218.
28
Yang M, Mattes J. 2008. Discovery, biology and therapeutic potential of RNA interference, microRNA and antagomirs. Pharmacol therap, 117: 94-104.
29
ORIGINAL_ARTICLE
Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa and Curcuma longa in rat kidney
Objective: Inflammation and oxidative stress is considered to have a crucial role in induction of nephropathy. Curcuma longa (C. longa) and Nigella sativa (N. sativa) have anti-inflammatory and antioxidant effects. This study was designed to investigate the effect of mixed hydro-alcoholic extract of N.sativa and C. longa on the oxidative stress induced by Adriamycin (ADR) in rat kidney. Material and Method: The animals were divided into 6 groups: control (CO), ADR, Adriamycin+ Vitamin C (ADR+VIT C), C. longa extract+ Adriamycin (C.LE+ADR), N. sativa extract+ Adriamycin (N.SE+ADR) and C. longa extract+ N. sativa extract + Adriamycin (N.S+C.L+ADR). ADR (5mg/kg) was injected intravenously, whereas VITC (100mg/kg) and extract of C. longa (1000mg/kg) and N. sativa (200mg/kg) were administrated orally. Finally, the renal tissue, urine and blood samples were collected and submitted to measure of redox markers, osmolarity and renal index. Results: The renal content of total thiol and superoxide dismutase (SOD) activity significantly decreased and Malondialdehyde (MDA) concentration increased in Adriamycin group compared to control group. The renal content of total thiol and SOD activity significantly enhanced and MDA concentration reduced in treated-mixed extract of C. longa and N. sativa along with ADR group compared to ADR group. The mixed extract did not restore increased renal index percentage induced by ADR. There also was no significant difference in urine and serum osmolarity between the groups. Conclusion: hydro-alcoholic extracts of N.sativa and C.longa led to an improvement in ADR-induced oxidative stress and mixed administration of the extracts enhanced the aforementioned therapeutic effect.
https://ajp.mums.ac.ir/article_5486_0ab36f65a0de28faf2c4ee50d8e468e1.pdf
2016-01-01
86
94
10.22038/ajp.2016.5486
Adriamycin
Nigella Sativa
Curcuma longa
Oxidative stress
Reza
Mohebbati
1
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammad Naser
Shafei
shafeimn@mums.ac.ir
2
Neurocognitive Research Center and department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mohammad
Soukhtanloo
asadasd@mums.ac.ir
3
Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Noema
Mohammadian Roshan
4
Department of Pathology, Qaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Abolfazl
Khajavi Rad
khajavirada@mums.ac.ir
5
Neurogenic Inflammation Research Center, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Akbar
Anaeigoudari
anaeiga901@mums.ac.ir
6
Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
AUTHOR
Sara
Hosseinian
hoseinians@mums.ac.ir
7
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Sareh
Karimi
8
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Farimah
Beheshti
beheshtif1@thums.ac.ir
9
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
1
Akram M, Uddin S, Ahmed A, Usmanghani K, Hannan A, Mohiuddin E, Asif M. 2001. Curcuma longa and curcumin: a review article. Rom J Biol, 55: 65–70.
2
Babu PS, Srinivasan K. 1997. Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats. Mol Cell Biochem, 166: 169-175.
3
Cizmarikova M, Podracka L, Klimcakov AL, Habalova V, Boor A, Mojzis J, Mirossay L. 2015. MDR1 polymorphisms and idiopathic nephrotic syndrome in Slovak children: preliminary results. Med Sci Monit, 21: 59-68.
4
Cohly H, Taylor A, Angel MF, Salahudeen AK. 1998. Effect of turmeric, turmerin and curcumin on H2O2-induced renal epithelial (LLC-PK1) cell injury. Free Radic Biol Med, 24: 49-54.
5
Antunes Lm, D'arc J, Bianchi Md. 2000. Protective effects of vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: a dose-dependent study. Pharmacological Research, 41: 405-411.
6
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. 2007. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine, 14: 621-627.
7
Jadhav VB, Thakare VN, Suralkar AA, Naik SR. 2013. Ameliorative effect of Luffa acutangula Roxb. on doxorubicin induced cardiac and oxidative stress in mice. Indian J Exp Biol, 51: 149-156.
8
Janero DR. 1990. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med, 9: 515-540.
9
Khan N, Sultana S. 2005. Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. Eur J Cancer Prev, 14: 159-168.
10
Khazdair MR. 2015. The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity. J Toxicol, 2015, 1-7.
11
Khorsandi L, Orazizadeh M. 2008. Protective effect of Curcuma longa extract on acetaminophen induced nephrotoxicity in mice. DARU, 16: 155-159.
12
Lee VW, Harris DC. 2011. Adriamycin nephropathy: a model of focal segmental glomerulosclerosis. Nephrology (Carlton), 16: 30-38.
13
Madesh M, Balasubramanian KA. 1998. Microtiter plate assay for superoxide dismutase using MTT reduction by superoxide. Indian J Biochem Biophys, 35: 184-188.
14
Medina-Navarro R, Corona-Candelas I, Barajas-Gonzalez S, Diaz-Flores M, Duran-Reyes G. 2014. Albumin antioxidant response to stress in diabetic nephropathy progression. PLoS One, 9: e106490.
15
Nakakura H, Ashida A, Hirano K, Tamai H. 2004. Oxidative stress in a rat model of nephrosis can be quantified by electron spin resonance. Pediatr Nephrol, 19: 266-270.
16
Omran OM. 2014. Effects of thymoquinone on STZ-induced diabetic nephropathy: an immunohistochemical study. Ultrastruct Pathol, 38: 26-33.
17
Quiles JL, Huertas JR, Battino M, Mataix, J, Ramirez-Tortosa MC. 2002. Antioxidant nutrients and adriamycin toxicity. Toxicology, 180: 79-95.
18
Rybi-Szuminska A, Wasilewska A, Michaluk-Skutnik J, Osipiuk-Remza B, Filonowicz R, Zajac M. 2014. Are oxidized low-density lipoprotein and C-reactive protein markers of atherosclerosis in nephrotic children? Ir J Med Sci, 184:775-780.
19
Salama SM, Abdulla MA, Alrashdi AS, Ismail S, Alkiyumi SS, Golbabapour S. 2013. Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats. BMC Complement Altern Med, 13: 56.
20
Saleem U, Ahmad B, Rehman K, Mahmood S, Alam M, Erum A. 2012. Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin associated oxidative stress in rabbits. Pak J Pharm Sci, 25: 727-730.
21
Sarhan M, El Serougy H, Hussein AM, El-Dosoky M, Sobh MA, Fouad SA, Sobh M, Elhusseini F. 2014. Impact of bone-marrow-derived mesenchymal stem cells on adriamycin-induced chronic nephropathy. Can J Physiol Pharmacol, 92: 733-743.
22
Sharma JB, Sharma A, Bahadur A, Vimala N, Satyam A, Mittal S. 2006. Oxidative stress markers and antioxidant levels in normal pregnancy and pre-eclampsia. Int J Gynaecol Obstet, 94: 23-27.
23
Sharma OP. 1976. Antioxidant activity of curcumin and related compounds. Biochem Pharmacol, 25: 1811-1812.
24
Staniek K, Gille L. 2010. Is thymoquinone an antioxidant? BMC Pharmacol, 10, A9.
25
Venkatesan N. 1998. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol, 124: 425-427.
26
Venkatesan N, Punithavathi D, Arumugam V. 2000. Curcumin prevents adriamycin oxidative stress in rats. Br J Pharmacol, 129: 231-234.
27
Zima T, Tesar V, Crkovska J, Stejskalova A, Platenik J, Teminova J, Nemecek K, Janebova M, Stipek S. 1998. ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats. Nephrol Dial Transplant, 13: 1975-1979.
28
ORIGINAL_ARTICLE
Effect of Nigella sativa on reproductive system in experimental menopause rat model
Objective: Menopause is the condition when regular menstrual periods cease and may be accompanied by psychological and physical symptoms. The purpose of current study was to determine Nigella sativa effects on reproductive system in experimental menopause animal models. Materials and Methods: A series of experiments wasconducted to investigate the effects of different dosages of N. sativa (first experiment), various extracts of N. sativa (second experiment)and some of its ingredients (third experiment) on selected menopausal parameters of ovariectomized (OVX) rats. Forty different OVX rats were equally divided into 5 groups and administered with one of the following treatments for 21 days: conjugated equine estrogen (positive control), distilled water or olive oil (negative control), treatment groups (N. sativa300, 600 and 1200 mg/kg in the first experiment), (300mg/kg methanol, hexane and SFE extracts of N. sativa in the second experiment) and (linoleic acid 50 mg/kg, gamma linolenic acid 10mg/kg, and thymoquinone 15mg/kg in the third experiment). Results: The results demonstrated that N.sativa exert estrogenic effect were exhibited through uterotrophic assay and vaginal cell cornification as well as blood estrogen level. Furthermore, low dose N. sativa, methanol extract and linoleic acid had prominent estrogenic like effects which were significantly different from those of control group (p<0.05) in different experiments. Conclusion: The finding indicated the probable beneficial role for N. sativa in the treatment of postmenopausal symptoms and possibility of using N. sativa as an alternative to hormone replacement therapy (HRT) for post menopause in human.
https://ajp.mums.ac.ir/article_6079_ec23387ad355c8703ce9358676f94559.pdf
2016-01-01
95
103
10.22038/ajp.2016.6079
Menopause
Nigella Sativa
Ovariectomized rats
Saadat
Parhizkar
parhizkarsa@gmail.com
1
Medicinal Plants Research Centre, Yasuj University of Medical Sciences, Yasuj, Iran
AUTHOR
Latiffah
Latiff
llatiffah@gmail.com
2
Department of Community Health, Faculty of Medicine and Health Sciences, University Putra Malaysia (UPM)
LEAD_AUTHOR
Ali
Parsa
parsa@iausr.ac.ir
3
Department of Chemistry, College of Science, Shahre Rey Branch, Islamic Azad University, Tehran, Iran
AUTHOR
Adlercreutz H, Mazur W. 1997. Phytoestrogens and western diseases. Ann Med, 29: 95-120.
1
Andrews WC. 1995. The transitional years and beyond. Obstet Gynecol, 85:1-5.
2
Anon. WHO Annual Report 2001, WHO Publication office, Geneva, Switzerland, 2003.
3
Babazadeh B, Sadeghnia HR, Safarpour Kapurchal E, Parsaee H, Nasri S. and Tayarani-Najaran Z. 2012. Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells. Avicenna J Phytomed, 2: 125-132.
4
Bones O. Menopause: What causes the menopause? Symptoms. Health risks. Medical News Today 17th July 2006.
5
Browngoehl LA. 2000. Osteoporosis. In: Giasois M, Garrison J, Hart AK, Lehmkuhl DL. Editors, Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX. pp. 1564–1575.
6
Bush TL. 2006. The Epidemiology of Cardiovascular Disease in Postmenopausal Women. Ann NY AcadSci, 592:263 – 271.
7
Cheikh-Rouhou S, Besbes S, Lognay G, Blecker C, Deroanne C, Attia H. 2008. Sterol composition of black cumin (Nigella sativa L.) and Aleppo pine (Pinushalepensis Mill.) seed oils. J Food Comp Anal, 21: 162–168.
8
Coad J, Dunstall M. 2005. Anatomy and Physiology for Midwives. Second ed.
9
Dollah MA, Parhizkar S, Izwan M. 2013a. Effect of Nigella sativa on the kidney function in rats. Avicenna J Phytomed, 2: 152-158.
10
Dollah MA, Parhizkar S, Latiff AL, Hassan MHB. 2013b. Toxicity Effect of Nigella Sativa on the Liver Function of Rats. Adv Pharm Bull, 3: 97-102.
11
Ginsburg J, Prelevic GM. 2000. Lack of significant hormonal effects and controlled trials of phytoestrogens. Lancet, 355: 163-164.
12
Haseena S, Aithal M, Das KK, Saheb SH. 2015. Effect of Nigella Sativa Seed Powder on Testosterone and LH levels in Sterptozotocine Induced Diabetes male Albino Rats. J Pharm Sci Res, 7: 234-237.
13
Hosseinzadeh H, Tafaghodi M, Jalal Mosavi M, Taghiabadi E. 2013. Effect of Aqueous and Ethanolic Extracts of Nigella sativa Seeds on Milk Production in Rats. J Acupunct Meridian Stud, 6:18-23.
14
Ibrahim MR, Hamdan NS , Mahmud R, Imam MU, Saini SM, Rashid SNA, Ghafar SA, Latiff LA and Ismail M.2014. A randomised controlled trial on hypolipidemic effects of Nigella Sativa seeds powder in menopausal women. J Transl Med, 12:82-89.
15
Keyhanmanesh R, Gholamnezhad Z, Boskabady MH. 2014. The relaxant effect of Nigella sativa on smooth muscles, it’s possible mechanisms and clinical applications. Iran J Basic Med Sci, 17:939-949
16
Latiff LA, Parhizkar S, Dollah MA, Syed TSH. 2014. Alternative supplement for enhancement of reproductive health and metabolic profile among perimenopausal women: a novel role of Nigella sativa. Iran J Basic Med Sci, 17:980-985.
17
Liu M, Xu X, Rang W, Li Y, Song Y. 2004. Influence of ovariectomy and 17β-estradiol treatment on insulin sensitivity, lipid metabolism and post-ischemic cardiac function. Int J Cardiol, 97: 485-493.
18
Parhizkar S, Rashid I, Latiffah AL. 2008. Incision Choice in Laparatomy: a Comparison of Two Incision Techniques in Ovariectomy of Rats. World Appl Sci J, 4: 537-540.
19
Ronda SR, Lele SS. 2008. Culture Conditions stimulating high γ-Linolenic Acid accumulation by Spirulina platensis. Braz J Microbiol, 39: 693-697.
20
Terenius L. 1971.The Allen-Doisy test for estrogens reinvestigated. Steroids, 17:653-661.
21
ORIGINAL_ARTICLE
The effects of Nigella sativa on sickness behavior induced by lipopolysaccharide in male Wistar rats
Objective: Neuroimmune factors contribute on the pathogenesis of sickness behaviors. Nigella sativa (NS) has anti-inflammatory, anti-anxiety and anti-depressive effects. In the present study, the effect of NS hydro-alcoholic extract on sickness behavior induced by lipopolysaccharide (LPS) was investigated. Materials and Methods: The rats were divided into five groups (n=10 in each): (1) control (saline), (2) LPS (1 mg/kg, administered two hours before behavioral tests), (3-5) LPS-Nigella sativa 100 , 200 and 400 mg/kg (LPS-NS 100, LPS-NS 200 and LPS-NS 400, respectively). Open- field (OF), elevated plus maze (EPM) and forced swimming test (FST) were performed. Results: In OF, LPS reduced the peripheral crossing, peripheral distance, total crossing and total distance compared to control (pConclusion: The results of the present study showed that the hydro-alcoholic extract of NS reduced the LPS-induced sickness behaviors in rats. Further investigations are required for better understanding the responsible compound (s) and the underlying mechanism(s).
https://ajp.mums.ac.ir/article_6205_ef004867d586346ccda0eb116b2165fd.pdf
2016-01-01
104
116
10.22038/ajp.2016.6205
Rat
Lipopolysaccharide
Nigella Sativa
Sickness behavior
Fatemeh
Norouzi
norouzif921@mums.ac.ir
1
Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Azam
Abareshi
abareshia921@mums.ac.ir
2
Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Akbar
Anaeigoudari
anaeiga901@mums.ac.ir
3
Department of Physiology, School of Medicine, Jiroft University of medical Sciences, Jiroft, Iran
AUTHOR
Mohammad Naser
Shafei
shafeimn@mums.ac.ir
4
Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Zahra
Gholamnezhad
5
Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Mohsen
Saeedjalali
saeedjalais@yahoo.com
6
Mashhad Technical Faculty, Technical and Vocational University, Mashhad, Iran
AUTHOR
Reza
Mohebati
mohebatir931@mums.a.cir
7
Department of Physiology School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
AUTHOR
Mahmoud
Hosseini
hosseinim@mums.ac.ir
8
Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
1
Ali BH, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. [Review]. Phytother Res, 17: 299-305.
2
Azizi-Malekabadi H, Hosseini M, Pourganji M, Zabihi H, Saeedjalali M, Anaeigoudari A. 2015a. Deletion of ovarian hormones induces a sickness behavior in rats comparable to the effect of lipopolysaccharide. Neurol Res Int, 627642.
3
Azizi-Malekabadi H, Pourganji M, Zabihi H, Saeedjalali M, Hosseini M. 2015 b. Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats. Arq Neuropsiquiatr, 73: 132-139.
4
Beheshti F, Hosseini M, Shafei MN, Soukhtanloo M, Ghasemi S, Vafaee F, Zarepoor L. 2014. The effects of Nigella sativa extract on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. Nutr Neurosci, DOI: http://dx.doi.org/10.1179/1476830514Y.0000000144.
5
Burton MD, Sparkman NL, Johnson RW. 2011. Inhibition of interleukin-6 trans-signaling in the brain facilitates recovery from lipopolysaccharide-induced sickness behavior. J Neuroinflammation, 8: 54.
6
Chourbaji S, Urani A, Inta I, Sanchis-Segura C, Brandwein C, Zink M, Schwaninger M, Gass P. 2006. IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiol Dis, 23: 587-594.
7
Contreras CM, Rodriguez-Landa Jf, Fau - Gutierrez-Garcia AG, Gutierrez-Garcia Ag, Fau - Bernal-Morales B, Bernal-Morales B. 2001. The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of lateral septal nucleus neurones in the rat. J Psychopharmacol, 15:231-6.
8
Coppen AJ, Doogan DP. 1988. Serotonin and its place in the pathogenesis of depression. J Clin Psychiatry, 49:4-11.
9
Dantzer R, O’Connor JC, Lawson MA, Kelley KW. 2011. Inflammation-associated depression: from serotonin to kynurenine. Psychoneuroendocrinology, 36: 426-436.
10
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim E K, Lanctôt KL. 2010. A meta-analysis of cytokines in major depression. Biol Psychiatry, 67: 446-457.
11
Dunn AJ.2000. Cytokine activation of the HPA axis. Ann N Y Acad Sci, 917: 608-617.
12
Dunn AJ. 2006. Effects of cytokines and infections on brain neurochemistry. Clin Neurosci Res, 6: 52-68.
13
Dunn A J, Wang J, Ando T. 1999. Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Adv Exp Med Biol, 1999;461:117-27.
14
El Gazzar MA. 2007. Thymoquinone suppressses in vitro production of IL-5 and IL-13 by mast cells in response to lipopolysaccharide stimulation. Inflamm Res, 56: 345-351.
15
el Tahir KE, Ashour MM, al-Harbi MM. 1993. The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: elucidation of the mechanism(s) of action. Gen Pharmacol, 24: 1115-1122.
16
Entok E, Ustuner MC, Ozbayer C, Tekin N, Akyuz F, Yangi B, Kurt H, Degirmenci I Gunes HV. 2014. Anti-inflammatuar and anti-oxidative effects of Nigella sativa L.: 18FDG-PET imaging of inflammation. Mol Biol Rep, 41: 2827-2834.
17
Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B. 2002. Microglial activation‐mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J Neurochem, 81: 1285-1297.
18
Gilhotra N, Dhingra D. 2011. Thymoquinone produced antianxiety-like effects in mice through modulation of GABA and NO levels. Pharmacol Rep, 63: 660-669.
19
Hajhashemi V, Ghannadi A, Jafarabadi H. 2004. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. [Research Support, Non-U.S. Gov't]. Phytother Res, 18: 195-199.
20
Helal GK. 2010. Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. Pak J Pharm Sci, 23: 131-137.
21
Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Sadeghnia HR, Soukhtanloo M. 2015. Effects of the hydro-alcoholic extract of Nigella Sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med, 21:438-44.
22
Hosseini M, Zakeri S, Khoshdast S, Yousefian FT, Rastegar M, Vafaee F, Kahdouee S, Ghorbani F, Rakhshandeh H, Kazemi SA. 2012. The effects of Nigella sativa hydro-alcoholic extract and thymoquinone on lipopolysaccharide-induced depression like behavior in rats. J Pharm Bioallied Sci, 4: 219.
23
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. 2007. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine, 14: 621-627.
24
Houghton PJ, Zarka R, de las Heras B, Hoult JR. 1995. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med, 61: 33-36.
25
Howren MB, Lamkin DM, Suls J. 2009. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med., 71: 171-186.
26
Hritcu L, Gorgan LD. 2014. Intranigral lipopolysaccharide induced anxiety and depression by altered BDNF mRNA expression in rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry, 51: 126-132.
27
Janssen DG, Caniato RN, Verster JC, Baune BT. 2010. A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Hum Psychopharmacol, 25: 201-215.
28
Kalus U, Pruss A, Bystron J, Jurecka M, Smekalova A, Lichius JJ, Kiesewetter H. 2003. Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. [Clinical Trial Randomized Controlled Trial]. Phytother Res, 17: 1209-1214.
29
Kang A, Hao H, Zheng X, Liang Y, Xie Y, Xie T, Dai C, Zhao Q, Wu X, Xie L. 2011. Peripheral anti-inflammatory effects explain the ginsenosides paradox between poor brain distribution and anti-depression efficacy. J Neuroinflammation, 8:100.
30
Lawson MA, Parrott JM, McCusker RH, Dantzer R, Kelley KW, O’Connor JC. 2013. Intracerebroventricular administration of lipopolysaccharide induces indoleamine-2, 3-dioxygenase-dependent depression-like behaviors. J Neuroinflammation, 10: 87.
31
Layé S, Gheusi G, Cremona S, Combe C, Kelley K, Dantzer R, Parnet P. 2000. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am J Physiol Regul Integr Comp Physiol, 279: R93-R98.
32
Leonard BE. 2001. The immune system, depression and the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry, 25: 767-780.
33
Ma XC, Jiang D, Jiang WH, Wang F, Jia M, Wu J, Hashimoto K, Dang YH, Gao CG. 2011. Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress. [Research Support, Non-U.S. Gov't]. PLoS One, 6: e20955.
34
Maes M, Berk M, Goehler L, Song C, Anderson G, Gałecki P, Leonard B. 2012. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med, 10: 66.
35
Maes M, Kubera M, Obuchowiczwa E, Goehler L, Brzeszcz J. 2011. Depression’s multiple comorbidities explained by (neuro) inflammatory and oxidative & nitrosative stress pathways. Neuroendocrinol Lett, 32: 7-24.
36
Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M. 2009. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis, 24: 27-53.
37
Mahgoub AA. 2003. Thymoquinone protects against experimental colitis in rats. Toxicol Lett, 143: 133-143.
38
Maier SF, Watkins LR. 1995. Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Res, 695: 279-282.
39
Miller AH. 2010. Depression and immunity: a role for T cells? Brain Behav Immun, 24: 1-8.
40
Mohamed A, Afridi DM, Garani O, Tucci M. 2005. Thymoquinone inhibits the activation of NF-kappaB in the brain and spinal cord of experimental autoimmune encephalomyelitis. Biomed Sci Instrum, 41: 388-393.
41
Neamati A, Chaman F, Hosseini M, Boskabady MH. 2014. The effects of Valeriana officinalis L. hydro-alcoholic extract on depression like behavior in ovalbumin sensitized rats. J Pharm Bioallied Sci, 6: 97-103.
42
Perveen T, Haider S, Kanwal S, Haleem DJ. 2009. Repeated administration of Nigella sativa decreases 5-HT turnover and produces anxiolytic effects in rats. Pak J Pharm Sci, 22: 139-144.
43
Petit-Demouliere B, Chenu F Fau - Bourin M, Bourin M.2005. Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology (Berl). 177:245-55.
44
Piser TM. 2010. Linking the cytokine and neurocircuitry hypotheses of depression: a translational framework for discovery and development of novel anti-depressants. Brain Behav Immun, 24: 515-524.
45
Pourbakhsh H, Taghiabadi E, Abnous K, Hariri AT, Hosseini SM, Hosseinzadeh H. 2014. Effect of Nigella sativa fixed oil on ethanol toxicity in rats. Iran J Basic Med Sci, 17: 1020-1031.
46
Pourganji M, Hosseini M, Soukhtanloo M, Zabihi H, Hadjzadeh MA. 2014. Protective role of endogenous ovarian hormones against learning and memory impairments and brain tissues oxidative damage induced by lipopolysaccharide. Iran Red Crescent Med J, 16:e13954.
47
Quan N, Sundar SK, Weiss JM. 1994. Induction of interleukin-1 in various brain regions after peripheral and central injections of lipopolysaccharide. J Neuroimmunol, 49: 125-134.
48
Raison CL, Capuron L, Miller AH. 2006. Cytokines sing the blues: inflammation and the pathogenesis of depression.
49
Trends Immunol, 27: 24-31.
50
Sharp LK, Lipsky MS. 2002. Screening for depression across the lifespan. Am Fam Physician, 66: 1001-1008.
51
Swamy SM, Tan BK. 2000. Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds. [Research Support, Non-U.S. Gov't]. J Ethnopharmacol, 70: 1-7.
52
Swiergiel AH, Dunn AJ. 2007. Effects of interleukin-1β and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests. Pharmacol Biochem Behav, 86: 651-659.
53
Szentirmai É, Krueger JM. 2014. Sickness behaviour after lipopolysaccharide treatment in ghrelin deficient mice. Brain Behav Immun, 36: 200-206.
54
Takao T, Culp SG, De Souza EB. 1993. Reciprocal modulation of interleukin-1 beta (IL-1 beta) and IL-1 receptors by lipopolysaccharide (endotoxin) treatment in the mouse brain-endocrine-immune axis. Endocrinology, 132: 1497-1504.
55
Taksande BG, Chopde CT, Umekar MJ, Kotagale NR. 2015. Agmatine attenuates lipopolysaccharide induced anorexia and sickness behavior in rats. Pharmacol Biochem Behav, 132: 108-114.
56
Tekeoglu I, Dogan A, EdizL, Budancamanak M, Demirel A. 2007. Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother Res, 21: 895-897.
57
Umar S, Zargan J, Umar K, Ahmad S, Katiyar CK, Khan HA. 2012. Modulation of the oxidative stress and inflammatory cytokine response by thymoquinone in the collagen induced arthritis in Wistar rats. Chem Biol Interact, 197: 40-46.
58
Vafaee F, Hosseini M, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, Seghatoleslam M, Mousavi SM, Amani A , Shafei MN. 2015. The Effects of Nigella Sativa Hydro-alcoholic Extract on Memory and Brain Tissues Oxidative Damage after Repeated Seizures in Rats. Iran J Pharm Res, 14: 547-557.
59
Vaillancourt F, Silva P, Shi Q, Fahmi H, Fernandes JC, Benderdour M. 2011. Elucidation of molecular mechanisms underlying the protective effects of thymoquinone against rheumatoid arthritis. [Research Support, Non-U.S. Gov't]. J Cell Biochem, 112: 107-117.
60
Wang Y, Gao H, Zhang W, Fang L. 2015. Thymoquinone inhibits lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells. Int Immunopharmacol, 26: 169-173.
61
Worthen DR, Ghosheh OA, Crooks PA. 1998. The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. [Research Support, Non-U.S. Gov't]. Anticancer Res, 18: 1527-1532.
62
ORIGINAL_ARTICLE
Safety evaluation of Phytovagex, a pessary formulation of Nigella sativa, on pregnant rats
Objective: The possible toxicity of drugs in pregnancy should be tested before their use in pregnant patients. In the present study, we aimed to evaluate the safety of phytovagex, a pessary formulation of Nigella sativa (N. sativa), which is already in clinical use for vaginal fungal infection. Materials and Methods: The pregnant rats were treated intravaginal with physiological saline (vehicle) or phytovagex pessary in the first half of their pregnancy (days 1 to 10 of gestation). Duration of pregnancy and health parameters of the newborns were recorded after parturition. Also, cytotoxicity of N. sativa hydroalcoholic extract was tested against ovary Cho cells. Results: The phytovagex had no significant effect on the duration of pregnancy, number of newborns, weight of neonates, and percent of stillbirth. No deformity or general behavioral abnormality was observed in neonates monitored for 30 days after birth. N. sativa extract had no significant effect on the viability of ovary cells at the concentrations of 12.5-200 µg/mL. Conclusion: Results of this animal study showed that phytovagex has no overall effect on the duration of pregnancy and health parameters of the newborns. Also, its active agent, N. sativa, does not induce any cytotoxic effect on ovary cells.
https://ajp.mums.ac.ir/article_6230_6da359bbad5f36be011359e383f739ce.pdf
2016-01-01
117
123
10.22038/ajp.2016.6230
Nigella Sativa
pregnancy
Rat
Stillbirth
Reza
Salarinia
salariniar891@mums.ac.ir
1
Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences
AUTHOR
Hassan
Rakhshandeh
rakhshandehh@mums.ac.ir
2
Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Davood
Oliaee
oliaeed901@mums.ac.ir
3
Student Research Committee, Mashhad University of Medical Sciences
AUTHOR
Sima Gul
Sima Gul Ghasemi
ghasemis901@mums.ac.ir
4
Neurogenic Inflammation Research Centre, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Ahmad
Ghorbani
ghorbania@mums.ac.ir
5
Pharmacological Research Center of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
AbuKhader MM, Khater SH, Al-Matubsi HY. 2013. Acute effects of thymoquinone on the pregnant rat and embryo-fetal development. Drug Chem Toxicol, 36: 27-34.
1
Al-Enazi MM. 2007. Effect of thymoquinone on malformations and oxidative stress-induced diabetic mice. Pak J Biol Sci, 10: 3115-3119.
2
Alinejad B, Ghorbani A, Sadeghnia HR. 2013. Effects of combinations of curcumin, linalool, rutin, safranal, and thymoquinone on glucose/serum deprivation-induced cell death. Avicenna J Phytomed, 3: 321-328.
3
Babazadeh B, Sadeghnia HR, Kapurchal ES, Parsaee H, Nasri S Tayarani-Najaran Z. 2012. Protective effect of Nigella sativa and thymoquinone on serum/glucose deprivation-induced DNA damage in PC12 cells. Avicenna J Phytomed, 2: 125-132.
4
Calixto JB. 2000. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz J Med Biol Res, 33: 179-189.
5
De Santis M, Straface G, Carducci B, Cavaliere AF, De Santis L, Lucchese A, Merola AM, Caruso A. 2004. Risk of drug-induced congenital defects. Eur J Obstet Gynecol Reprod Biol, 117: 10-19.
6
De Smet PAGM. 2004. Health risks of herbal remedies: an update. Clin Pharmacol Ther, 76: 1-17.
7
Dollah MA, Parhizkar S, Izwan M. 2013. Effect of Nigella sativa on the kidney function in rats. Avicenna J Phytomed, 3: 152-158.
8
Forouzanfar F, Fazly BSB, Hosseinzadeh H. 2015. Black cumin (Nigella sativa) and its constituent (thymoquinone): A review on antimicrobial effects. Iran J Basic Med Sci, 17: 929-938.
9
Ghorbani A, Asadpour E, Sadeghnia HR. 2015. Mechanism of protective effect of lettuce against glucose/serum deprivation-induced neurotoxicity. Nutr Neurosci, 18: 103-109.
10
Ghorbani A, Hadjzadeh MR, Rajaei Z, Zendehbad SB. 2014. Effects of fenugreek seeds on adipogenesis and lipolysis in normal and diabetic rat. Pak J Biol Sci, 17: 523-528.
11
Ghorbani A. 2013a. Best herbs for managing diabetes: a review of clinical studies. Braz J Pharm Sci, 49: 413-422.
12
Ghorbani A. 2013b. Phytotherapy for diabetic dyslipidemia: evidence from clinical trials. Clin Lipidol, 8: 311-319.
13
Goel G, Makkar HP, Francis G, Becker K. 2007. Phorbol esters: structure, biological activity, and toxicity in animals. Int J Toxicol, 26: 279-88.
14
Hadi V, Kheirouri S, Alizadeh M, Khabbazi A, Hosseini H. 2015. Effects of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress status in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial. Avicenna J Phytomed, in press.
15
Hosseini A, GhorbaniA. 2015. Cancer therapy with phytochemicals: evidence from clinical studies. Avicenna J Phytomed, 5: 84-97.
16
Jordan SA, Cunningham DG, Marles RJ. 2010. Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxicol Appl Pharmacol. 243: 198-216.
17
Keshri G, Singh M, Lakshmi V, Kamboj V. 1995. Post-coital contraceptive efficacy of the seeds of Nigella sativa in rats. Indian J physiol pharmacol, 39: 59-62.
18
Korgun ET, Dohr G, Desoye G, Demir R, Kayisli UA, Hahn T. 2003. Expression of insulin, insulin-like growth factor I and glucocorticoid receptor in rat uterus and embryo during decidualization, implantation and organogenesis. Reproduction, 125: 75-84.
19
Mollazadeh H, Hosseinzadeh H. 2014. The protective effect of Nigella Sativa against liver injury: a review. Iran J Basic Med Sci, 17: 958-966.
20
Nickavar B, Mojab F, Javidnia K, Amoli MR. 2003. Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Z Naturforsch C, 58: 629-631.
21
Oliaee D, Boroushaki MT, Oliaee N, Ghorbani A. 2014. Evaluation of cytotoxicity and antifertility effects of Artemisia Kopetdaghensis. Adv Pharmacol Sci, 2014: 745760.
22
Peters P, Miller RK, Schaefer C. Drugs during pregnancy and lactation: treatment options and risk assessment. Schaefer C, Peters PWJ, Miller RK (eds). 3rd edition. 2015. Elsevier. San Diego, CA, USA. pp. 1-21.
23
Rakhshandeh H, Vahdati-Mashhadian N, khajekaramadini M. 2011. In vitro and in vivo study of the antibacterial effects of Nigella sativa methanol extract in dairy cow mastitis. Avicenna J Phytomed, 1: 29-35.
24
Shafiee-Nick R, Ghorbani A, Vafaee F, Rakhshandeh H. 2012. Chronic administration of a combination of six herbs inhibits the progression of hyperglycemia and decreases serum lipids and aspartate amino transferase activity in diabetic rats. Adv Pharmacol Sci, 2012, 789796.
25
Shafiq H, Ahmad A, Masud T, Kaleem M. 2014. Cardio-protective and anti-cancer therapeutic potential of Nigella sativa. Iran J Basic Med Sci, 17: 967-979.
26
Sun F, Akazawa S, Sugahara K, Kamihira S, Kawasaki E, Eguchi K, Koji T. 2002. Apoptosis in normal rat embryo tissues during early organogenesis: the possible involvement of Bax and Bcl-2. Arch Histol Cytol, 65: 145-157.
27
Vahdati-Mashhadian N, Rakhshandeh H, Omidi A. 2005. An investigation on LD50 and subacute hepatic toxicity of Nigella sativa seed extracts in mice. Pharmazie, 60: 544-547.
28
Wan Ezumi MF, Amrah SS, Suhaimi A, Mohsin S. 2007. Evaluation of the female reproductive toxicity of aqueous extract of Labisia pumila var. alata in rats. Indian J Pharmacol, 39: 30-32.
29
Xia HF1, Cao JL, Jin XH, Ma X. 2013. MiR199a is implicated in embryo implantation by regulating Grb10 in rat. Reproduction, 147: 91-99.
30
Yadav S, Agarwal M. 2011. Effect of Nigella sativa on the estrous cycle and ovarian activity in albino rats. Pharmacologyonline, 3: 997-1006.
31
ORIGINAL_ARTICLE
Neuropharmacological effects of Nigella sativa
Nigella sativa (NS) (Ranunculaceae family) is generally utilized as a therapeutic plant all over the world. The seeds of the plant have a long history of use in different frameworks of medicines and food. In Islamic literature, it is considered as one of the greatest forms of therapeutics. It has been widely used to treat nervous system diseases such as memory impairment, epilepsy, neurotoxicity, pain, etc. Additionally, this is uncovered that the majority of therapeutic properties of this plant are due to the presence of thymoquinone (TQ) which is a major bioactive component of the essential oil. Pharmacological studies have been done to evaluate the effects of NS on the central nervous system (CNS). The present review is an effort to provide a detailed scientific literature survey about pharmacological activities of the plant on nervous system. Our literature review showed that NS and its components can be considered as promising agents in the treatment of nervous system disorders.
https://ajp.mums.ac.ir/article_6231_ee096bb7dc46cbffd3d0c875ac50c04c.pdf
2016-01-01
124
141
10.22038/ajp.2016.6231
Nigella Sativa
Thymoquinone
Central nervous system
Neuropharmacological effects
Farimah
Beheshti
beheshtif1@thums.ac.ir
1
Departments of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Majid
Khazaei
khazaeim@mums.ac.ir
2
Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
AUTHOR
Mahmoud
Hosseini
hosseinim@mums.ac.ir
3
Neurocognitive Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
LEAD_AUTHOR
Abdel-Daim MM, Ghazy EW. 2015. Effects of Nigella sativa oil and ascorbic acid against oxytetracycline-induced hepato-renal toxicity in rabbits. Iran J Basic Med Sci, 18: 221.
1
Abdel-Fattah AM, Matsumoto K, Watanabe, H. 2000. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol, 400: 89-97.
2
Abdel-Zaher AO, Abdel-Rahman MS, Elwasei FM. 2011. Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: role of nitric oxide and oxidative stress. Neurotoxicology,32: 725-733.
3
Abel-Salam BK. 2012. Immunomodulatory effects of black seedsand garlic on alloxan-induced diabetes in albino rat. Allergol Immunopathol (Madr), 40: 336-340.
4
Adams EH, Breiner S, Cicero TJ, Geller A, Inciardi JA, Schnoll SH, Senay EC, Woody GE. 2006. A comparison of the abuse liability of tramadol, NSAIDs, and hydrocodone in patients with chronic pain. J Pain Symptom Manage, 31: 465-476.
5
Adewale OO, Brimson JM, Odunola OA, Gbadegesin MA, Owumi SE, Isidoro C, Tencomnao T. 2015. The Potential for Plant Derivatives against Acrylamide Neurotoxicity. Phytother Res.
6
Adnan LHM, Bakar NHA, Mohamad N. 2014. Opioid dependence and substitution therapy: thymoquinone as potential novel supplement therapy for better outcome for methadone maintenance therapy substitution therapy. Iran J Basic Med Sci, 17: 926.
7
Ahmad A, Husain A, Mujeeb M, Khan S A, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
8
Akhondian J, Kianifar H, Raoofziaee M, Moayedpour A, Toosi MB, Khajedaluee M. 2011. The effect of thymoquinone on intractable pediatric seizures (pilot study). Epilepsy Res, 93: 39-43.
9
Akhondian J, Parsa A, Rakhshande H. 2007. The effect of Nigella sativa L. (black cumin seed) on intractable pediatric seizures. Med Sci Monit, 13: CR555-559.
10
Akhtar M, Maikiyo AM, Khanam R, Mujeeb M, Aqil M, Najmi AK. 2012 . Ameliorating effects of two extracts of Nigella sativa in middle cerebral artery occluded rat. J Pharm Bioallied Sci, 4: 7075.
11
Akhtar M, Maikiyo AM, Najmi AK, Khanam R, Mujeeb M, Aqil M. 2013. Neuroprotective effects of chloroform and petroleum ether extracts of Nigella sativa seeds in stroke model of rat. J Pharm Bioallied Sci, 5: 119-125.
12
Al-Ali A, Alkhawajah AA, Randhawa MA, Shaikh NA. 2008. Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats. J Ayub Med Coll Abbottabad, 20: 25-27.
13
Al-Ghamdi MS. 2001. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol, 76: 45-48.
14
Ali BH, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. Phytother Res, 17: 299-305.
15
Al-Jassir MS. 1992. Chemical composition and microflora of black cumin (Nigella sativa L.) seeds growing in Saudi Arabia. Food Chem, 45: 239-242.
16
Al-Majed AA., Al-Omar FA, Nagi MN. 2006. Neuroprotective effects of thymoquinone against transient forebrain ischemia in the rat hippocampus. Eur J Pharmacol, 543: 40-47.
17
Al Mofleh IA, Alhaider AA, Mossa JS, Al-Sohaibani MO, Al-Yahya MA, Rafatullah S, Shaik SA. 2008. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi J Gastroenterol, 14: 128.
18
Al-Naggar TB, Gomez-Serranillos MP, Carretero ME, Villar AM. 2003. Neuropharmacological activity of Nigella sativa L. extracts. J Ethnopharmacol 88: 63-68.
19
Alhebshi A, Odawara A, Gotoh M, Suzuki I. 2013. Thymoquinone protects cul-tured hippocampal and human induced pluripotent stem cells-derived neuronsagainst α-synuclein-induced synapse damage. Neurosci Lett, 570: 126-131.
20
Alhebshi AH, Gotoh M, Suzuki I. 2013. Thymoquinone protects cultured rat primary neurons against amyloid beta-induced neurotoxicity. Biochem Biophys Res Commun, 433: 362-367.
21
Amin B, Taheri MM, Hosseinzadeh H. 2014. Effects of intraperitoneal thymoquinone on chronic neuropathic pain in rats. Planta Med, 80: 1269-1277.
22
Ansari AA, Hassan S, Kenne L, Wehler T. 1988. Structural studies on a saponin isolated from Nigella sativa. Phytochemistry, 27: 3977-3979.
23
Anvari M, Seddigh A, Shafei MN, Rakhshandeh H, Talebi AH, Tahani MR, Saeedjalal SM, Hosseini M. 2012. Nigella sativa extract affects conditioned place preference induced by morphine in rats. Anc Sci Life, 32: 82-88.
24
Ashraf M, Ali Q, Iqbal Z. 2006. Effect of nitrogen application rate on the content and composition of oil, essential oil and minerals in black cumin (Nigella sativa L.) seeds. J Sci Food Agr, 86: 871-876.
25
Atta MB. 2003. Some characteristics of nigella (Nigella sativa L.) seed cultivated in Egypt and its lipid profile. Food Chem, 83: 63-68.
26
Azizi-Malekabadi H, Pourganji M, Zabihi H, Saeedjalali M, Hosseini M. 2015. Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats. Arq Neuropsiquiatr, 73: 132-139.
27
Bailey CJ, Day C. 1989. Traditional plant medicines as treatments for diabetes. Diabetes care, 12: 553-564.
28
Barbee JG. 1998. Mixed symptoms and syndromes of anxiety and depression: diagnostic, prognostic, and etiologic issues. Ann Clin Psychiatry, 10: 15-29.
29
Bashir MU, Qureshi HJ. 2010. Analgesic effect of Nigella sativa seeds extract on experimentally induced pain in albino mice. J Coll Physicians Surg Pak, 20: 464-467.
30
Beheshti F, Hosseini M, Shafei MN, Soukhtanloo M, Ghasemi S, Vafaee F, Zarepoor L. 2014. The effects of Nigella sativa extract on hypothyroidism-associated learning and memory impairment during neonatal and juvenile growth in rats. Nutr Neurosci. DOI: http://dx.doi.org/10.1179/1476830514Y.0000000144.
31
Beheshti F, Hosseini M, Vafaee F, Shafei MN, Soukhtanloo M. 2015. Feeding of Nigella sativa during neonatal and juvenile growth improves learning and memory of rats. J Tradit Complement Med. doi:10.1016/j.jtcme.2014.11.039.
32
Bielekova B, Martin R. 2004. Development of biomarkers in multiple sclerosis. Brain, 127: 1463-1478.
33
Bin Sayeed MS, Asaduzzaman M, Morshed H, Hossain MM, Kadir MF, Rahman MR. 2013. The effect of Nigella sativa Linn. seed on memory, attention and cognition in healthy human volunteers. J Ethnopharmacol, 148: 780-786.
34
Biswas D, Guha D. 2007. “Nigella sativa: its role as an anticonvulsant in pentylenetetrazole induced seizures”. Biogenic Amines, 21: 66-76.
35
Boskabady MH, Keyhanmanesh R, Khamneh S, Ebrahimi MA. 2011a. The effect of Nigella sativa extract on tracheal responsiveness and lung inflammation in ovalbumin-sensitized guinea pigs. Clinics (Sao Paulo), 66:879-87.
36
Boskabady MH, Vahedi N, Amery S, Khakzad MR. 2011b. The effect of Nigella sativa alone, and in combination with dexamethasone, on tracheal muscle responsiveness and lung inflammation in sulfur mustard exposed guinea pigs. J Ethnopharmacol, 137:1028-34.
37
Bourgou S, Ksouri R, Bellila A, Skandrani I, Falleh H, Marzouk B. 2008. Phenolic composition and biological activities of Tunisian Nigella sativa L. shoots and roots. C R Biol, 331: 48-55.
38
Casson RJ, Chidlow G, Ebneter A, Wood JP, Crowston J, Goldberg I. 2012. Translational neuroprotection research in glaucoma: a review of definitions and principles. Clin Experiment Ophthalmol, 40: 350-357.
39
Chatap VK, Sharma DK, Parial SD, Nangude TD, Khan M. 2006. Nigella sativa Linn: A Golden Seed. Int J Plant Sci , 1: 357-360.
40
Cheikh-Rouhou S, Besbes S, Lognay G, Blecker C, Deroanne C, Attia H. 2008. Sterol composition of black cumin (Nigella sativa L.) and Aleppo pine (Pinus halpensis Mill.) seed oils. J Food Comp Anal, 21: 162-168.
41
Dahri AH, Chandiol AM, Rahoo AA, Memon RA. 2005. Effect of Nigella sativa (kalonji) on serum cholesterol of albino rats. J Ayub Med Coll Abbottabad, 17: 72-74.
42
Darakhshan S, Pour AB, Colagar AH, Sisakhtnezhad S. 2015. Thymoquinone and its therapeutic potentials. Pharmacol Res, 95: 138-158.
43
Denenberg VH. 1969. Open-field bheavior in the rat: what does it mean? Ann N Y Acad Sci, 159: 852-859.
44
Dickson DW, Feany MB, Yen SH, Mattiace LA, Davies P. 1996. Cytoskeletal pathology in non-Alzheimer degenerative dementia: new lesions in diffuse Lewy body disease, Pick's disease, and corticobasal degeneration. J Neural Transm Suppl, 47: 31-46.
45
Eddy NB, Leimbach D. 1953. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J Pharmacol Exp Ther, 107: 385-393.
46
El-Marasy SA, El-Shenawy SM, El-Khatib AS, Shabrawy OA, Kenawy SA. 2012. “Effect of Nigella sativa and wheat germ oils on scopolamine-induced memory impairment in rats”. Bull Fac Pharm Cairo Univ, 50: 81-88.
47
El-Naggar T, Gomez-Serranillos MP, Palomino OM, Arce C, Carretero ME. 2010. Nigella sativa L. seed extract modulates the neurotransmitter amino acids release in cultured neurons in vitro. J Biomed Biotechnol, 2010: 398312.
48
El Sherbiny DA, Khalifa AE, Attia AS, Eldenshary EES. 2003. Hypericum perforatum extract demonstrates antioxidant properties against elevated rat brain oxidative status induced by amnestic dose of scopolamine. Pharmacol Biochem Behav, 76: 523-533.
49
Elmansy RA, Almasry SM. 2013. Morphological and Immunohistochemical Analysis of the Effects of Thymoquinone on the Neurovascular Component of Jejunal Submucosa of Diabetic Rat Model. J Am Sci, 9.
50
Eltony SA, Elgayar SA. 2014. Histological study on effect of Nigella sativa on aged olfactory system of female albino rat. Rom J Morphol Embryol, 55: 325-334.
51
Ersahin M, Toklu HZ, Akakin D, Yuksel M, Yegen BC, Sener G. 2011. The effects of Nigella sativa against oxidative injury in a rat model of subarachnoid hemorrhage. Acta Neurochir (Wien), 153: 333-341.
52
Eun JJ, Ki YL, Seung HK, Sang HS, Young CK. 2008. Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treate dmice. Eur J Pharmacol, 588: 78-84.
53
Ezz HS, Khadrawy YA, Noor NA. 2011. The neuroprotective effect of curcumin and Nigella sativa oil against oxidative stress in the pilocarpine model of epilepsy: a comparison with valproate. Neurochem Res, 36: 2195-2204.
54
Gella A, Durany N. 2009. Oxidative stress in Alzheimer′s disease. Cell Adh Migr, 3: 88-93.
55
Gholamnezhad Z, Boskabady MH, Hosseini M. 2014. Effect of Nigella sativa on immune response in treadmill exercised rat. BMC Complement Altern Med, 14: 437.
56
Gilani A, Jabeen Q, Ullah khan M. 2004. A review of medicinal uses and pharmacological activities of Nigella sativa. Pak J Biol Sci, 7: 441-451.
57
Gilani AH, Aziz N, Khurram IM, Chaudhary KS, Iqbal A. 2001. Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): a traditional herbal product with multiple medicinal uses. J Pak Med Assoc, 51: 115-120.
58
Gilhotra N, Dhingra D. 2011. Thymoquinone produced antianxietylike effects in mice through modulation of GABA and NO levels. Pharmacol Rep, 63: 660-669.
59
Goreja WG. 2003. Black seed: Nature’s Miracle Remedy. New York, NY: Amazing Herbs Press.
60
Grandjean P, Landrigan PJ. 2006. Developmental neurotoxicity of industrial chemicals. Lancet, 368: 2167-2178.
61
Greene LA, Tischler AS. 1976. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A, 73: 2424-2428.
62
Guha D, Biswas D, Purkayastha S. 2005. Suppression of penicillin-induced epileptiform activity by Nigella sativa: possible mediation by neurotransmitters. Biogenic Amines, 19: 309-321.
63
Hajhashemi V, Ghannadi A, Jafarabadi H. 2004. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother Res, 18: 195-199.
64
Hanafy MSM, Hatem ME. 1991. Studies on the antimicrobial activity of Nigella sativa seed (black cumin). J Ethnopharmacol, 34: 275-278.
65
Hasselmo ME. 2006. The role of acetylcholine in learning and memory. Curr Opin Neurobiol, 16: 710-715.
66
Hobbenaghi R, Javanbakht J, Sadeghzadeh Sh, Kheradmand D, Abdi FS, Jaberi MH, Mohammadiyan MR, Khadivar F, Mollaei Y. 2014. Neuroprotective effects of Nigella sativa extract on cell death in hippocampal neurons following experimental global cerebral ischemia-reperfusion injury in rats. J Neurol Sci, 337: 74-79.
67
Hosseini M, Alaei H, Eslamizadeh MJ, Safarzadeh F. 2007. Effect of morphine self-administration on water and food intake in rat. Iran J Basic Med Sci, 169-175.
68
Hosseini M, Alaei HA, Naderi A, Sharifi MR, Zahed R. 2009. Treadmill exercise reduces self-administration of morphine in male rats. Pathophysiology, 16: 3-7.
69
Hosseini M, Zakeri S, Khoshdast S, Yousefian FT, Rastegar M, Vafaee F, Kahdouee S, Ghorbani F, Rakhshandeh H, Kazemi SA. 2012. The effects of Nigella sativa hydro-alcoholic extract and thymoquinone on lipopolysaccharide - induced depression like behavior in rats. J Pharm Bioallied Sci, 4: 219-225.
70
Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Sadeghnia HR, Soukhtanloo M. 2014. Effects of the hydro-alcoholic extract of Nigella Sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med, 1-7.
71
Hosseini M, Mohammadpour T, Karami R, Rajaei Z, Sadeghnia HR., Soukhtanloo M. 2015. Effects of the hydro-alcoholic extract of Nigella sativa on scopolamine-induced spatial memory impairment in rats and its possible mechanism. Chin J Integr Med, 21: 438-444.
72
Hosseinzadeh H, Parvardeh S. 2004. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine, 11: 56-64.
73
Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri MT. 2005. Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit, 11: BR106-110.
74
Ishiyama T, Tokuda K, Ishibashi T, Ito A, Toma S, Ohno Y. 2007. Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. Eur J Pharmacol, 572: 160-170.
75
Ismail M, Yaheya M. 2009. Therapeutic role of prophetic medicine Habbat El Baraka (Nigella sativa L.)-A review. World Appl Sci J, 7: 1203-1208.
76
Ismail N, Ismail M, Mazlan M, Latiff LA, Imam MU, Iqbal S, Azmi NH, Ghafar SA, Chan KW. 2013. Thymoquinone prevents beta-amyloid neurotoxicity in primary cultured cerebellar granule neurons. Cell Mol Neurobiol, 33: 1159-1169.
77
Jalali MR, Roghani M. 2009. “The effect of Nigella sativa on learning and memory in male diabetic rats”. Basic Clin Neurosci, 1: 32-34.
78
Javanbakht J, Hobbenaghi R, Hosseini E, Bahrami AM, Khadivar F, Fathi S, Hassan MA. 2013. Histopathological investigation of neuroprotective effects of Nigella sativa on motor neurons anterior horn spinal cord after sciatic nerve crush in rats. Pathol Biol (Paris), 61: 250-253.
79
Jukic M, Politeo O, Maksimovic M, Milos M. 2007. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother Res, 21: 259-261.
80
Kanter M. 2008. Nigella sativa and derived thymoquinone prevents hippocampal neurodegeneration after chronic toluene exposure in rats. Neurochem Res, 33: 579-588.
81
Kanter M, Coskun O, Budancamanak M. 2005. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol, 11: 6684-6688.
82
Kapoor S. 2009. Emerging clinical and therapeutic applications of Nigella sativa in gastroenterology. World J Gastroenterol,
83
15:2170-1.
84
Karami M, Zarrindast MR. 2011. Place Aversion by Morphine in Offspring Born of Female Morphine Administered Wistar Rats. Iran j pharm res, 10: 577.
85
Keyhanmanesh R, Gholamnezhad Z, Boskabady MH.2014a.The relaxant effect of Nigella sativa on smooth muscles, its possible mechanisms and clinical applications. Iran J Basic Med Sci, 17:939-49.
86
Keyhanmanesh R, Nazemiyeh H, Mazouchian H, Bagheri Asl MM, Karimi Shoar M, Alipour MR, Boskabady MH. 2014b. Nigella sativa Pretreatment in Guinea Pigs Exposed to Cigarette Smoke Modulates In Vitro Tracheal Responsiveness. Iran Red Crescent Med J, 16.
87
Khan MAU, Ashfaq MK, Zuberi, HS, Mahmood MS, Gilani AH. 2003. The in vivo antifungal activity of the aqueous xtract from Nigella sativa seeds. Phytother Res, 17:183-186.
88
Khare CP. 2004. Encyclopedia of Indian medicinal plants. NewYork: Springes-Verlag Berlin Heidelberg.
89
Khoddami A, Ghazali HM, Yassoralipour A, Ramakrishnan Y, Ganjloo A. 2011. Physicochemical characteristics of nigella seed (Nigella sativa L.) oil as affected by different extraction methods. J Am Oil Chem Soc, 88: 533-540.
90
Liu MY, Wang S, Yao WF, Zhang ZJ, Zhong X, Sha L, He M, Zheng ZH, Wei MJ. 2014. Memantine improves spatial learning and memory impairments by regulating NGF signaling in APP/PS1 transgenic mice. Neuroscience, 273: 141-151.
91
Malenka RC, Nestler EJ, Hyman SE. 2009. Reinforcement and Addictive Disorders. In A. Sydor & R. Y. Brown (Eds.), Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed., pp. 364-375. New York: McGraw-Hill Medical.
92
Ming H, Chen R, Wang J, Ju J, Sun L, Zhang G. 2014. [Role of hippocampal neuronal intracellular calcium overload in modulating cognitive dysfunction and the neuronprotective effect of mematine in a mouse model of chronic intermittent hypoxia]. Zhonghua Jie He He Hu Xi Xi Ji Bing Za Zhi, 37: 893-897.
93
Mohamed A, Waris HM, Ramadan H, Quereshi M, Kalra J. 2009. Amelioration of chronic relapsing experimental autoimmune encephalomyelitis (cr-eae) using thymoquinone. Biomed Sci Instrum, 45: 274-279.
94
Morikawa T, Xu F, Kashima Y, Matsuda H, Ninomiya K, Oshikawa M. (2004. Noveldolabellane-type diterpene alkaloids with lipidmetabolism promoting activities from the seeds of Nigella sativa. Org Lett, 6: 869-872.
95
Mousavi G, Mohajeri D. 2014. Effect of ground black seeds (Nigella sativa L.) on renal tubular cell apoptosis induced by ischemia/reperfusion injury in the rats. Iran J Basic Med Sci, 17: 1032.
96
Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. 2010. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death. Cell Mol. Neurobiol, 30: 591-598.
97
Nabeshima T. 1993. Behavioral aspects of cholinergic transmission: role of basal forebrain cholinergic system in learning and memory. Prog Brain Res, 98: 405-411.
98
Nickavar B, Mojab F, Javidnia K, Amoli MA. 2003. Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran. Z Naturforsch C, 58: 629-631.
99
Paarakh PM. 2010. Nigella sativa Linn.–A comprehensive review. Indian J Nat Prod Resour, 1: 409-429.
100
Pellow S, Chopin P, File SE, Briley M. 1985. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods, 14: 149-167.
101
Perveen T, Abdullah A, Haider S, Sonia B, Munawar AS, Haleem DJ. 2008. Long-term administration of Nigella sativa effects nociceotion and improves learning and memory in rats. Pak J Biochem Mol Biol, 41: 141-143.
102
Perveen T, Haider S, Kanwal S, Haleem DJ. 2009. Repeated administration of Nigella sativa decreases 5-HTturnover and produces anxiolytic effects in rats. Pak J Pharm Sci, 22: 139-144.
103
Petit-Demouliere B, Chenu F, Bourin M. 2005. Forced swimming test in mice: a review of antidepressant activity. Psychopharmacology, 177: 245-255.
104
Pourbakhsh H, Taghiabadi E, Abnou, K, Hariri AT, Hosseini SM, Hosseinzadeh H. 2014. Effect of Nigella sativa fixed oil on ethanol toxicity in rats. Iran J Basic Med Sci, 17: 1020.
105
Radad K, Moldzio R, Taha M, Rausch WD. 2009. Thymoquinone protects dopaminergic neurons against MPP+ and rotenone. Phytother Res, 23: 696-700.
106
Rajsekhar S, Kuldeep B. 2011. Pharmacognosy and pharmacology of Nigella sativa- A review. Int Res J Pharm, 2: 36-39.
107
Randhawa MA, Alghamdi MS. 2011. Anticancer activity of Nigella sativa (black seed)- a review. Am J Chin Med, 39: 1075-1091.
108
Razavi BM, Hosseinzadeh H. 2014. A review of the effects of Nigella sativa L. and its constituent, thymoquinone, in metabolic syndrome. J Endocrinol Invest, 37: 1031-1040.
109
Rogers J, Webster S, Lue LF, Brachova L, Civin WH, Emmerling M, Shivers B, Walker D, McGeer P. 1996. Inflammation and Alzheimer′s disease pathogenesis. Neurobiol Aging, 17: 681-686.
110
Sahak MK, Mohamed AM, Hashim NH, Hasan Adli DS. 2013. Nigella sativa Oil Enhances the Spatial Working Memory Performance of Rats on a Radial Arm Maze. Evid Based Complement Alternat Med, 2013: 180598.
111
Sangi S, Ahmed SP, Channa MA, Ashfaq M, Mastoi SM. 2008. A new and novel treatment of opioid dependence: Nigella sativa 500 mg. J Ayub Med Coll Abbottabad, 20: 118-124.
112
Sedaghat R, Roghani M, Khalili M. 2014. Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran J Pharm Res, 13: 227-234.
113
Sharma NK, Ahirwar D, Jhade D, Gupta S. 2009. Medicinal and phamacological potential of nigella sativa: a review. Ethnobotanical Leaflets, 2009: 11.
114
Sharp LK, Lipsky MS. 2002. Screening for depression across the lifespan: a review of measures for use in primary care settings. Am Fam Physician, 66:1001-8.
115
Sharrif M. 2011. Nigella sativa Traditional Usages (BlackSeed). Adv Environ Biol, 5: 5-16.
116
Shrivastava RM, Agrawal RC, Parveen ZJ. 2011. A review on therapeutic applications of Nigella sativa. J Chem Chem Sci, 1: 241-248.
117
Spillantini MG, Schmidt ML, Lee VMY, Trojanowski JQ, Jakes R, Goedert M. 1997. α-Synuclein in Lewy bodies. Nature, 388: 839-840.
118
Türkdoğan MK, Ağaoğlu Z, Yener Z, Sekeroğlu R, Akkan HA, Avci ME. 2001. The role of antioxidant vitamins (C and E), selenium and Nigella sativa in the prevention of liver fibrosis and cirrhosis in rabbits: new hopes. DTW. Dtsch Tierarztl Wochenschr, 108: 71-73.
119
Ullah I, Ullah N, Naseer MI, Lee HY, Kim MO. 2012. Neuroprotection with metformin and thymoquinone against ethanol-induced apoptotic neurodegeneration in prenatal rat cortical neurons. BMC Neurosci, 13: 11.
120
Vafaee F, Hosseini M, Hassanzadeh Z, Edalatmanesh MA, Sadeghnia HR, Seghatoleslam M, Mousavi SM, Amani A, Shafei MN. 2015. The Effects of Nigella Sativa Hydro-alcoholic Extract on Memory and Brain Tissues Oxidative Damage after Repeated Seizures in Rats. Iran J Pharm Res, 14: 547.
121
Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature protocols, 1: 848-858.
122
Warrier PK, Nambiar VPK. 2004. Indian medicinal plants-a compendium of 500 species. Orient Longman Pvt Ltd, 139-142.
123
Yarnell E, Abascal K. 2011. Nigella sativa: holy herb of the middle East. Altern Compl Therap, 17: 99-105.
124
Yassin MM. 2005. Prophylactic Efficacy of Crushed Garlic Lobes, BlackSeed or Olive Oils on Cholinesterase Activity in Central Nervous System Parts and Serum of Lead In toxicated Rabbits. Turk J Biol, 29: 173-180.
125