Protective effects of long-term administration of Ziziphus jujuba fruit extract on cardiovascular responses in L-NAME hypertensive rats

Document Type : Original Research Article

Authors

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

2 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

3 Neurogenic Inflammation Research Centre, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Neurogenic Inflammation Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective: Ziziphus jujuba stimulates the release of nitric oxide (NO).  Because NO is involved in cardiovascular regulations, in this study the effects of hydroalcoholic extract of Z. jujuba on cardiovascular responses in acute NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats were evaluated.
Materials and Methods: Rats were divided into 6 group (n=6): 1) saline, 2) L-NAME received (10mg/kg) intravenously, 3) sodium nitroprusside (SNP) (50µg/kg)+L-NAME group received SNP before L-NAME and 4-6) three groups of Z. jujuba (100, 200 and 400mg/kg) that treated for four weeks and on the 28th day, L-NAME was injected. Femoral artery and vein were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously. Maximal changes (∆) of SBP, MAP and HR were calculated and compared to control and L-NAME groups.
Results: In L-NAME group, maximal ΔSBP (L-NAME: 44.15±4.0 mmHg vs control: 0.71±2.1 mmHg) and ΔMAP (L-NAME: 40.8±4.0 mmHg vs control: 0.57±1.6 mmHg) significantly increased (p0.05). All doses of Z. jujuba attenuated maximal ∆SBP and ∆MAP induced by L-NAME but only the lowest dose (100 mg/kg) had significant effects (ΔSBP: 20.36±5.6 mmHg vs L-NAME: 44.1±4.0 mmHg and ΔMAP: 20.8±4.5 mmHg vs L-NAME: 40.8±3.8 mmHg (p0.05).
Conclusion: Because long-term consumption of Z. jujuba extract, especially its lowest dose, attenuated cardiovascular responses induced by L-NAME, we suggest that Z. jujuba has potential beneficial effects in prevention of hypertension induced by NO deficiency.

Keywords

Main Subjects

References

Abbasnezhad A, Khazdair MR, Kianmehr M.  2016. The role of nitric oxide on the oxytocin induce analgesia in mice.  Iran J Basic Med Sci, 19: 238-244.
Achike FI, Kwan CY. 2003. Nitric oxide, human diseases and the herbal products that affect the nitric oxide signalling pathway. Clin Exp Pharmacol Physiol, 30:605-615.
Al-Reza SM, Yoon JI, Kim HJ, Kim JS, Kang SC .2010. Anti-inflammatory activity of seed essential oil from Zizyphus jujuba. Food Chem Toxicol, 48:639-643.
Banting JD, Friberg P, Adams MA. 1996. acute hypertension after nitric oxide synthase inhibition is mediated primarily by increased endothelin vasoconstriction. J Hypertens, 14:975-82.
Biancardi VC, Bergamaschi CT, Lopes OU, Campos RR. 2007. Sympathetic activation in rats with L-NAME-induced hypertension. Braz J Med Biol Res, 40:401-8.
Cheng G, Bai Y, Zhao Y, Tao J, Liu Y, Tu G, Ma L, LiaO N, XU X. 2000. Flavonoids from Ziziphus jujuba Mill var. spinosa. Tetrahedron, 56:8915-8920.
Fadel PJ. 2017. Nitric Oxide and Cardiovascular Regulation. Am Heart Assoc, 2017:778-779.
Fisher NDL, Hughes M, Gerhard-Herman M, Hollenberg NK. 2003. Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J Hypertens, 21:2281-2286.
Freedman JE, Parker C, Li L, Perlman JA, Frei B, Ivanov V, Deak LR, Iafrati MD, Folts JD. 2001. Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation,  103:2792-2798.
Gao Q-H, Wu C-S, Wang M. 2013. the jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits. J Agric Food Chem, 61:3351-3363.
Goyal R, Sharma PL, Singh M. 2011. Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat. J Nat Med, 65:514-518.
Han YJ, Kwon YG, Chung HT, Lee SK, Simmons RL, Billiar TR, Kim YM. 2001. Antioxidant enzymes suppress nitric oxide production through the inhibition of NF-κB activation: role of H2O2 and nitric oxide in inducible nitric oxide synthase expression in macrophages. Nitric Oxide, 5:504-513.
Hirschl MM, Binder M, Bur A, Herkner H, Müllner M, Woisetschläger C, Laggner AN. 1997. Safety and efficacy of urapidil and sodium nitroprusside in the treatment of hypertensive emergencies. Intensive Care Med, 23:885-888.
Hu CT, Chang KC, Wu CY, Chen HI. 1997. Acute effects of nitric oxide blockade with L‐NAME on arterial haemodynamics in the rat. Br J Pharmacol, 122:1237-1243.
Huang X, Kojima-Yuasa A, Norikura T, Kennedy DO, Hasuma T, Matsui-Yuasa I. 2007. Mechanism of the anti-cancer activity of Zizyphus jujuba in HepG2 cells. Am J Chin Med, 35:517-532.
Jerkic M, Rivas-Elena JV, Prieto M, et al. 2004. Endoglin regulates nitric oxide-dependent vasodilatation. FASEB J, 18:609-611.
Khayyal MT, El-Ghazaly MA, Abdallah DM, Nassar NN, Okpanyi SN, Kreuter M-H, 2002. Blood Pressure Lowering Effect of an Olive Leaf Extract {Olea europaed) in L-NAME Induced Hypertension in Rats. Arzneimittelforschung, 52:797-802.
Kim H, Han S. 1996. Zizyphus jujuba and Codonopsis pilosula stimulate nitric oxide release in cultured endothelial cells and kidney tissues. Asia Pac J Pharmacol, 11:121-128.
Klimaschewski L, Kummer W, Mayer B, et al. 1992. Nitric oxide synthase in cardiac nerve fibers and neurons of rat and guinea pig heart. Circ Res, 71:1533-1537.
Mahajan RT, Chopda M. 2009. Phyto-Pharmacology of Ziziphus jujuba Mill-A plant review. Pharmacogn Rev, 3:320 -329.
Mohebbati R, Iranmanesh M, Beheshti F, et al. 2016. The Effect of Some Herbal Extracts on Nitric Oxide Production in Endothelial Cells 3T3 Cell Line. Iran J Pharm Sinc, 12:1-10.
Mohebbati R, Shafei MN, Soukhtanloo M, Roshan NM, Rad AK, Anaeigoudari A, Hosseinian S, Karimi S, Beheshti F. 2016. Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa and Curcuma longa in rat kidney. Avicenna J Phytomed, 6:86-94.
Morley JE, Farr SA, Sell RL, Hileman SM, Banks WA. 2011. Nitric oxide is a central component in neuropeptide regulation of appetite. Peptides, 32:776-780.
Naseem KM. 2005. The role of nitric oxide in cardiovascular diseases. Mol Aspects Med, 26:33-65.
Sasser JM, Molnar M, Baylis C. 2011. Relaxin ameliorates hypertension and increases nitric oxide metabolite excretion in angiotensin II but not Nω-nitro-L-arginine methyl ester hypertensive rats. Hypertension, 58:197-204.
Savoia C, Schiffrin EL. 2006. Inflammation in hypertension. Curr Opin Nephrol Hypertens, 15:152-158.
Schulz E, Gori T, Münzel T. 2011. Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res, 34:665-673.
Shafei MN, Nasimi A. 2011. Effect of glutamate stimulation of the cuneiform nucleus on cardiovascular regulation in anesthetized rats: Role of the pontine Kolliker–Fuse nucleus. Brain Res, 1385:135-143.
Steinkamp-Fenske K, Bollinger L, Xu H, Yao Y, Horke S, Förstermann U, Li H. 2007. Reciprocal regulation of endothelial nitric-oxide synthase and NADPH oxidase by betulinic acid in human endothelial cells. J Pharmacol Exp Ther, 322:836-842.
Stewart DE. 2004. Venlafaxine and sour date nut. A J Psychiatry, 161:1129.
Taati M, Alirezaei M, Meshkatalsadat M, Rasoulian B, Kheradmand A, Neamati S. 2011. Antioxidant effects of aqueous fruit extract of Ziziphus jujuba on ethanol-induced oxidative stress in the rat testes. Iran J Vet Res, 12:39-45.
Wang D, Zhao Y, Jiao Y, Yu L, Yang S, Yang X. 2012. Antioxidative and hepatoprotective effects of the polysaccharides from Zizyphus jujube cv. Shaanbeitanzao. Carbohydr Polym, 88:1453-1459.
Xiaoling H, Zhiyun X, Yi N, Jinliang L, Xianqiong F. 1992. Outline of the Investigation on the leaf of F. tataricum bythe Means of Traditional Chinese Medicine and Western Modem Medicine. 470-476.
Zhang D, Yuan B, Sun H. 2002. the effect of jujuboside on rats with spontaneous hypertension. J Xi'an Jiaotong Univers, 24:59-60.
Zhang H, Jiang L, Ye S, Ye Y, Ren F. 2010. Systematic evaluation of antioxidant capacities of the ethanolic extract of different tissues of jujube (Ziziphus jujuba Mill.) from China. Food Chem Toxicol, 48:1461-1465.
Zhao Y, Zhang X, Li J, Bian Y, Sheng M, Liu B, Fu Z, Zhang Y, Yang B. 2016. Jujuboside B Reduces Vascular Tension by Increasing Ca 2+ Influx and Activating Endothelial Nitric Oxide Synthase. PloS one, 11:149386.
Zicha J, Dobešová Z, Kuneš J. 2006. Antihypertensive mechanisms of chronic captopril or N-acetylcysteine treatment in L-NAME hypertensive rats. Hypertens Res, 29:1021-1027.
Avicenna Journal of Phytomedicine
Volume 8, Issue 2
March and April 2018
Pages 143-151

Files

Share

How to cite

Statistics