Antioxidant and hepatoprotective effects of Artemisia dracunculus against CCl4-induced hepatotoxicity in rats

Document Type: Original Research Article

Authors

1 Behbahan Faculty of Medical Sciences, Behbahan, Iran

2 Nutrition Research Center, Department of Biochemistry and Diet Therapy, Faculty of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Biochemistry and clinical laboratories, Faculty of Medicine, Tabriz University of medical sciences, Tabriz, Iran

4 Department of Biology, Faculty of Science, Shahid Chamran University, Ahvaz, Iran

5 Behbahan Faculty of medical sciences, Behbahan, Iran

Abstract

Objective: The present study was conducted to investigate the antioxidant and hepatoprotective activity of the hydro-alcoholic extract of aerial parts of Artemisia dracunculus (HAAD) against CCl4-induced hepatotoxicity in rats.
Materials and Methods: The antioxidant activity was evaluated by reducing power, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 20-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Rats were pre-treated with either 50, 100, and 200 mg/kg of HAAD or silymarin (100 mg/kg; served as the positive control group) for 15 days and they received a single dose of CCl4 on the last day. Hepatoprotective effects were investigated by assessment of serum biochemical enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein (TP), total bilirubin (TB), malondialdehyde (MDA), and antioxidant enzymes (SOD, CAT, GST and GSH), along with histopathological studies.
Results: Total phenolic content was 197.22±3.73 mg gallic acid equivalent/g HAAD dry weight. HAAD indicated powerful activity in FRAP, DPPH and ABTS tests. Acute toxicity study showed that the extract had an LD50 of >5000 mg/kg. Oral treatment with HAAD exhibited a significant decrease in the levels of AST, ALT, ALP and TB and an increase in the level of TP. The extract significantly diminished MDA levels. The activities of the antioxidant enzymes were significantly augmented in rats pretreated with HAAD 200 mg/kg. Histopathological examination demonstrated lower liver damage in HAAD-treated groups as compared to CCl4 groups.
Conclusion: Our findings indicated hepatoprotective effects of the hydro-alcoholic extract of A. dracunculus on CCl4-induced hepatic damage in rats and suggested that these effects may be produced by reducing oxidative stress.

Keywords

Main Subjects


Aglarova AM. 2006. Comparative Analysis of Secondary Metabolites of Artemisia dracunculus L., Russian and French cultivars. Ph. D. thesis, Mahachkala.

Ali H, Kabir N, Muhammad A, Shah MR, Musharraf SG, Iqbal N, Nadeem S. 2014. Hautriwaic acid as one of the hepatoprotective constituent of Dodonaea viscosa. Phytomedicine, 21P: 131-140.

Amresh G, Rao CV, Singh PN. 2007. Antioxidant activity of Cissampelos pareira on benzo (a) pyrene-induced mucosal injury in mice. Nutr Res, 27: 625-632.

Azeem, A, Mathew M, Nair C. 2010. Hepatoprotective effect of Averrhoea carambola fruit extract on carbon tetrachloride induced hepatotoxicity in mice. Asian Pac J Trop Med, 3: 610-613.

Benli M, Kaya I, Yigit N. 2007. Screening antimicrobial activity of various extracts of Artemisia dracunculus L. Cell Biochem Funct, 25: 681-686.

Canabady-Rochelle LLS, Harscoat-Schiavo C, Kessler V, Aymes A, Fournier F,Girardet JM. 2015. Determination of reducing power and metal chelating ability of antioxidant peptides: Revisited methods. Food Chem, 183: 129-135.

Cheng N, Ren N, Gao H, Lei X, Zheng J, Cao W. 2013. Antioxidant and hepatoprotective effects of Schisandra chinensis pollen extract on CCl4-induced acute liver damage in mice. Food Chem Toxicol, 55: 234-240.

Debbache N, Atmani D, Atmani D. 2014. Chemical analysis and biological activities of Populus nigra, flower buds extracts as source of propolis in Algeria. Ind Crop Prod, 53: 85-92.

Eisenman SW, Struwe L. 2011. The global distribution of wild tarragon (Artemisia dracunculus L.; Asteraceae) cytotypes with twenty-seven new records from North America. Genet Resour Crop Ev, 58: 1199-1212.

Fuda H, Watanabe M, Hui SP, Joko S, Okabe H, Jin S, Takeda S, Miki E, Watanabe T, Chiba H. 2015. Anti-apoptotic effects of novel phenolic antioxidant isolated from the Pacific oyster (Crassostrea gigas) on cultured human hepatocytes under oxidative stress. Food Chem, 176: 226-233.

Gnanadesigan M, Ravikumar S, Inbaneson SJ. 2011. Hepatoprotective and antioxidant properties of marine halophyte Luminetzera racemosa bark extract in CCL4 induced hepatotoxicity. Asian Pac J Trop Med, 4: 462-465.

Gülçin İ, Huyut Z, Elmastaş M, Aboul-Enein HY. 2010. Radical scavenging and antioxidant activity of tannic acid. Arab J Chem, 3: 43-53.

Gupta RK, Hussain T, Panigrahi G, DasA, Singh GN, Sweety K Faiyazuddin M,  Rao CV. 2011. Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals. Asian Pac J Trop Med, 4: 964-968.

Hua D, Zhang D, Huang B, Yi P, Yan C. 2014. Structural characterization and DPPH· radical scavenging activity of a polysaccharide from Guara fruits. Carbohyd Polym, 103: 143-147.

Huang Q, Zhang S, Zheng L, He M, Huang R, Lin X. 2012. Hepatoprotective effects of total saponins isolated from Taraphochlamys affinis against carbon tetrachloride induced liver injury in rats. Food Chem Toxicol, 50: 713-718.

Jalali Ghassam B, Ghaffari H, Prakash HS, Kini KR. 2014. Antioxidant and hepatoprotective effects of Solanum xanthocarpum leaf extracts against CCl4-induced liver injury in rats. Pharm Biol, 52: 1060-1068.

Jiang Y, Fan X, Wang Y, Tan H, Chen P, Zeng H, Huang M,. Bi H. 2015. Hepato-protective effects of six schisandra lignans on acetaminophen-induced liver injury are partially associated with the inhibition of CYP-mediated bioactivation. Chem Biol Interact, 231: 83-89.

Kepekçi RA, Polat S, Çelik A, Bayat N, Saygideger SD. 2013. Protective effect of Spirulina platensis enriched in phenolic compounds against hepatotoxicity induced by CCl4. Food Chem, 141: 1972-1979.

Kheterpal I, Coleman L, Ku G, Wang ZQ, Ribnicky D, Cefalu WT. 2010. Regulation of insulin action by an extract of Artemisia dracunculus L. in primary human skeletal muscle culture: a proteomics approach. Phytother Res, 24: 1278-1284.

Khodakov GV, Kotikov IV, Pankovetskii VN. 2009. Component composition of essential oil from Artemisia abrotanum and A. dracunculus. Chem Nat Compd, 45: 905-908.

Kordali S, Kotan R, Mavi A, Cakir A, Ala A, Yildirim A. 2005. Determination of the chemical composition and antioxidant activity of the essential oil of Artemisia dracunculus and of the antifungal and antibacterial activities of Turkish Artemisia absinthium, A. dracunculus, Artemisia santonicum, and Artemisia spicigera essential oils. J Agr Food Chem, 53: 9452-9458.

Kumar D, Bhat ZA, Shah MY. 2012. Effect of successive extracts of Stachys tibetica Vatke (Lamiaceae) in anxiety. Orient Pharm Exp Med, 12: 247-253.

Li C, Yi LT, Geng D, Han YY, Weng Lj. 2015. Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice. Pharm Biol, 53: 767-772.

Lopes-Lutz D, Alviano DS, Alviano CS, Kolodziejczyk PP. 2008. Screening of chemical composition, antimicrobial and antioxidant activities of Artemisia essential oils. Phytochemistry, 69: 1732-1738.

Maheshwari DT, Yogendra Kumar MS, Verma SK, Singh VK, Singh SN. 2011. Antioxidant and hepatoprotective activities of phenolic rich fraction of Seabuckthorn (Hippophae rhamnoides L.) leaves. Food Chem Toxicol, 49: 2422-2428.

Manns MP, Wedemeyer H, Cornberg, M. 2006. Treating viral hepatitis C: efficacy, side effects, and complications. Gut, 55: 1350-1359.

Obolskiy D, Pischel I, Feistel B, Glotov N, Heinrich M. 2011. Artemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety. J Agr Food Chem, 59: 11367-11384.

Pappas RS, Sturtz G. 2001. Unusual alkynes found in the essential oil of Artemisia dracunculus L. var. dracunculus from the Pacific Northwest. J Essent Oil Res, 13: 187-188.

Pareek A, Godavarthi A, Issarani R, Nagori BP. 2013. Antioxidant and hepatoprotective activity of Fagonia schweinfurthii (Hadidi) Hadidi extract in carbon tetrachloride induced hepatotoxicity in HepG2 cell line and rats. J Ethnopharmacol, 150: 973-981.

Raj S, Gothandam KM. 2014. Hepatoprotective effect of polyphenols rich methanolic extract of Amorphophallus commutatus var. wayanadensis against CCl4 induced hepatic injury in swiss albino mice. Food Chem Toxicol, 67: 105-112.

Rajabian A, Khayyat MH, Emami SA, Tayarani-Najaran Z, Oskooie RR, Asili J. Phytochemical Evaluation and Antioxidant Activity of Essential Oil, and Aqueous and Organic Extracts of Artemisia dracunculus. Jundishapur. J. Nat. Pharm. Prod. 2016 Nov (Inpress).

Roby MHH, Sarhan MA, Selim KAH, Khalel KI. 2013. Evaluation of antioxidant activity, total phenols and phenolic compounds in thyme (Thymus vulgaris L.), sage (Salvia officinalis L.), and marjoram (Origanum majorana L.) extracts. Ind Crop Prod, 43: 827-831.

Sadeghi H, Zarezade V, Sadeghi H, Akbartabar Toori M, Jafari Barmak M, Azizi A, Ghavamizadeh M, Mostafazadeh M. 2014. Anti-inflammatory Activity of Stachys Pilifera Benth. Iran Red Crescent Med J, 16:9.

Sayyah M, Nadjafnia L, Kamalinejad M. 2004. Anticonvulsant activity and chemical composition of Artemisia dracunculus L. essential oil. J Ethnopharmacol, 94: 283-287.

Schaich KM, Tian X, Xie J. 2015. Hurdles and pitfalls in measuring antioxidant efficacy: A critical evaluation of ABTS, DPPH, and ORAC assays. J Funct Foods, 14: 111-125.

Shah MD, Gnanaraj C, Haque ATME, Iqbal M. 2015. Antioxidative and chemopreventive effects of Nephrolepis biserrata against carbon tetrachloride (CCl4)-induced oxidative stress and hepatic dysfunction in rats. Pharm Biol, 53: 31-39.

Shahriyary L, Yazdanparast R. 2007. Inhibition of blood platelet adhesion, aggregation and secretion by Artemisia dracunculus leaves extracts. J Ethnopharmacol, 114: 194-198.

Singhal KG, Gupta GD. 2012. Hepatoprotective and antioxidant activity of methanolic extract of flowers of Nerium oleander against CCl4–induced liver injury in rats. Asian Pac J Trop Med, 5: 677-685.

Toori MA, Joodi B, Sadeghi H, Sadeghi H, Jafari M, Talebianpoor MS, Mehraban F, Mostafazadeh M, Ghavamizadeh M. 2015. Hepatoprotective activity of aerial parts of Otostegia persica against carbon tetrachloride-induced liver damage in rats. Avicenna J Phytomed, 5.3: 238-246.

Vuda M, D'Souza R, Upadhya S, Kumar V, Rao N, Kumar V, Boillat C, Mungli P. 2012. Hepatoprotective and antioxidant activity of aqueous extract of Hybanthus enneaspermus against CCl4-induced liver injury in rats. Exp Toxicol Pathol, 64: 855-859.

Zeashan H, Amresh G, Singh S, Rao CV. 2008. Hepatoprotective activity of Amaranthus spinosus in experimental animals. Food Chem Toxicol, 46: 3417-3421.

Zhang P, Li XM, Wang JN, Li X, Wang BG. 2015. New butenolide derivatives from the marine-derived fungus Paecilomyces variotii with DPPH radical scavenging activity. Phytochem Lett, 11: 85-88.

Zhou D, Ruan J, Cai Y, Xiong Z, Fu W, Wei A. 2010. Antioxidant and hepatoprotective activity of ethanol extract of Arachniodes exilis (Hance) Ching. J Ethnopharmacol, 129: 232-237.