Nigella sativa seed decreases endothelial dysfunction in streptozotocin-induced diabetic rat aorta

Document Type : Original Research Article

Authors

1 Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

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.

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References

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.
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.
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.
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.
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.
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.
De Vriese AS, Verbeuren TJ, Van De Voorde J, Lameire NH, Vanhoutte PM. 2000. Endothelial dysfunction in diabetes. Br J Pharmacol, 130: 963-974.
Dehkordi FR,  Kamkhah AF. 2008. Antihypertensive effect of N. sativa seed extract in patients with mild hypertension. Fundam Clin Pharmacol, 22: 447-452.
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.
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.
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.
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.
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.
Hartge MM, Unger T, KintscherU. 2007. The endothelium and vascular inflammation in diabetes. Diab Vasc Dis Res, 4: 84-88.
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.
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.
Katakam PV, Ujhelyi MR, Hoenig M, Miller AW. 2000. Metformin improves vascular function in insulin-resistant rats. Hypertension, 35: 108-112.
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.
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.
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.
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.
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.
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.
Nergiz C, Otles S. 1993. Chemical composition of Nigella sativa L. seeds. Food Chemistry, 48: 259-261.
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.
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.
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.
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.
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.
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.
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.
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.
Thorneloe KS, Nelson MT. 2005. Ion channels in smooth muscle: regulators of intracellular calcium and contractility. Can J Physiol Pharmacol, 83: 215-242.
Xu J, Zou MH. 2009. Molecular insights and therapeutic targets for diabetic endothelial dysfunction. Circulation Circulation, 120: 1266-86
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.
Zou MH, Cohen R, Ullrich V. 2004. Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium, 11: 89-97.
Avicenna Journal of Phytomedicine
Volume 6, Issue 1 - Serial Number 1
January and February 2016
Pages 67-76

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