@2024 Afarand., IRAN
ISSN: 2252-0805 The Horizon of Medical Sciences 2018;24(4):309-315
ISSN: 2252-0805 The Horizon of Medical Sciences 2018;24(4):309-315
Effect of Intrapertonal Injection of Crocin on Cardiovascular Parameters in Angiotensin II- Induced Hypertensive Rats
ARTICLE INFO
Article Type
Original ResearchAuthors
Anaeigoudari A. (1)Faramarzi A. (2)
Abbasnezhad A. (3)
Shafei M.N (*)
(*) Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
(1) Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran
(2) Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
(3) Department of Physiology, Faculty of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran
Correspondence
Address: Neurogenic Inflammation Research Centre, Mashhad University of Medical Sciences, Mashhad, IranPhone: +98-51-38828565
Fax: +98-51-38828564
Shafeimn@mums.ac.ir
Article History
Received: June 6, 2018Accepted: September 22, 2018
ePublished: October 10, 2018
ABSTRACT
Aims
The antihypertensive effect intravenous injection of Cronin has been
observed in our previous study. In this study, the effect of intraperitoneal (ip)
injection of Crocin on hypertension induced by angiotensin II (Ang II) with dose
of 50 ng/kg was investigated in rats.
Materials & Methods In current excremental study, thirty male Wistar rats were randomly divided into 5 groups: Control (Cont), Ang II50, Losartan (Los) + Ang II, (Cro) 100 + Ang II and Cro200 + Ang II (n = 6 in each group). To induce hypertension, Ang II (50 ng/kg, i.v) was administered. Los (10 mg/kg, i.v) and Cro (100 and 200 mg/kg, ip) were administered 30 min before Ang II. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) after cannulation of the artery were continuously recorded by power lab system then,(Δ;difference before and after injection) were calculated and compared between the groups. Differences were considered significant when P< 0.05.
Findings Ang II significantly increased SBP, MAP and decreased HR in several minutes (P<0.001). Losartan reduced these effects of angiotensin II. Pre-treatment with crocin (ip) significantly attenuated increased SBP and MAP induced by AngII (P<0.01) but it has not important effect on HR
Conclusion Injection of crocin (ip) and it's effect on the AT1 receptor reduces hypertension induced by the dose of 50 ng/kg of Ang II, which is comparable to that of Losartan. Therefore, the cardiovascular effect of crocin probably is mediated by this receptor of AngII.
Materials & Methods In current excremental study, thirty male Wistar rats were randomly divided into 5 groups: Control (Cont), Ang II50, Losartan (Los) + Ang II, (Cro) 100 + Ang II and Cro200 + Ang II (n = 6 in each group). To induce hypertension, Ang II (50 ng/kg, i.v) was administered. Los (10 mg/kg, i.v) and Cro (100 and 200 mg/kg, ip) were administered 30 min before Ang II. Systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (HR) after cannulation of the artery were continuously recorded by power lab system then,(Δ;difference before and after injection) were calculated and compared between the groups. Differences were considered significant when P< 0.05.
Findings Ang II significantly increased SBP, MAP and decreased HR in several minutes (P<0.001). Losartan reduced these effects of angiotensin II. Pre-treatment with crocin (ip) significantly attenuated increased SBP and MAP induced by AngII (P<0.01) but it has not important effect on HR
Conclusion Injection of crocin (ip) and it's effect on the AT1 receptor reduces hypertension induced by the dose of 50 ng/kg of Ang II, which is comparable to that of Losartan. Therefore, the cardiovascular effect of crocin probably is mediated by this receptor of AngII.
CITATION LINKS
[1]Wang J, Xiong X. Outcome measures of Chinese herbal medicine for hypertension: An overview of systematic reviews. Evid Based Complement Alternat Med. 2012;2012:697237.
[2]Macmahon S, Alderman MH, Lindholm LH, Liu L, Sanchez RA, Seedat YK. Blood-pressure-related disease is a global health priority. Am J Hypertend. 2008;21(8):843-4.
[3]Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: Analysis of worldwide data. Lancet. 2005;365(9455):217-23.
[4]Shafei MN, Faramarzi A, Khajavi Rad A, Anaeigoudari A. Crocin prevents acute angiotensin II-induced hypertension in anesthetized rats. Avicenna J Phytomed. 2017;7(4):345-52.
[5]Ferreira JC, Bacurau AV, Evangelista FS, Coelho MA, Oliveira EM, Casarini DE, et al. The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice. Am J Physiol Regul Integ Comp Physiol. 2008;294(1):R26-32.
[6]Mehta PK, Griendling KK. Angiotensin II cell signaling: Physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292(1):C82-97.
[7]Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling KK, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation, contribution to alterations of vasomotor tone. J Clin Invest. 1996;97(8):1916-23.
[8]Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini D, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45(2):205-51.
[9]Cockcroft JR. ACE inhibition in hypertension: Focus on perindopril. Am J Cardiovasc Drugs. 2007;7(5):303-17.
[10]Xu H, Chen Kj. Complementary and alternative medicine: Is it possible to be mainstream?. Chin J Integr Med. 2012;18(6):403-4.
[11]Hosseinzadeh H, Ziaee T, Sadeghi A. The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats. Phytomedicine. 2008;15(6-7):491-5.
[12]José Bagur M, Alonso Salinas GL, Jiménez-Monreal AM, Chaouqi S, Llorens S, Martínez-Tomé M, et al. Saffron: An old medicinal plant and a potential novel functional food. Molecules. 2017;23(1):30.
[13]Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: A comprehensive review. Food Chem Toxicol. 2014;64:65-80.
[14]Hosseinzadeh H, Shamsaie F, Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharmacogn Mag. 2009;5(20):419-24.
[15]Sun Y, Xu HJ, Zhao YX, Wang LZ, Sun LR, Wang Z, et al. Crocin exhibits antitumor effects on human leukemia HL-60 cells in vitro and in vivo. Evid Based Complement Alternat Med. 2013;2013:690164.
[16]Goyal SN, Arora S, Sharma AK, Joshi S, Ray R, Bhatia J, et al. Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats. Phytomedicine. 2010;17(3-4):227-32.
[17]Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res. 2010;24(7):990-4.
[18]Razavi BM, Hosseinzadeh H, Movassaghi AR, Imenshahidi M, Abnous K. Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. Chem Biol Interact. 2013;203(3):547-55.
[19]Ghods R, Gharouni M, Amanlou M, Sharifi N, Ghobadi A, Amin G. Effect of Onopordon acanthium L. as add on antihypertensive therapy in patients with primary hypertension taking losartan: A pilot study. Adv Pharm Bull. 2018;8(1):69-75.
[20]Sever PS, Messerli FH. Hypertension management 2011: Optimal combination therapy. Eur Heart J. 2011;32(20):2499-506.
[21]Gebre AK, Altaye BM, Atey TM, Tuem KB, Berhe DF. Targeting renin–angiotensin system against alzheimer’s disease. Front Pharmacol. 2018;9:440.
[22]Atlas SA. The renin-angiotensin aldosterone system: Pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007;13(8 Supp B):9-20.
[23]Dasgupta C, Zhang L. Angiotensin II receptors and drug discovery in cardiovascular disease. Drug Discov Today. 2011;16(1-2):22-34.
[24]Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Nati Acad Sci USA. 2006;103(47):17985-90.
[25]Mancini A, Serrano-Díaz J, Nava E, D'alessandro AM, Alonso GL, Carmona M, et al. Crocetin, a carotenoid derived from saffron (Crocus sativus L.), improves acetylcholine-induced vascular relaxation in hypertension. J Vasc Res. 2014;51(5):393-404.
[26]He SY, Qian ZY, Tang FT. Effect of crocin on intracellular calcium concentration in cultured bovine aortic smooth muscle cells. Yao Xue Xue Bao. 2004;39(10):778-81.
[27]Boskabady MH, Shafei MN, Shakiba A, Sang Sefidi H. Effect of aqueous‐ethanol extract from Crocus sativus (saffron) on guinea‐pig isolated heart. Phytother Res. 2008;22(3):330-4.
[28]Kander MC, Cui Y, Liu Z. Gender difference in oxidative stress: A new look at the mechanisms for cardiovascular diseases. J Cell Mol Med. 2017;21(5):1024-32.
[29]Chandra M, Surendra K, Kapoor RK, Ghatak A, Kaur G, Pandey NR, et al. Oxidant stress mechanisms in heart failure. Boll Chim Farm. 2000;139(3)149-52.
[30]Bashar T, Akhter N. Study on oxidative stress and antioxidant level in patients of acute myocardial infarction before and after regular treatment. Bangladesh Med Res Counc Bull. 2014;40(2):79-84.
[31]Zheng YQ, Liu JX, Wang JN, Xu L. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res. 2007;1138:86-94.
[32]Wang Y, Wang Q, Yu W, Du H. Crocin attenuates oxidative stress and myocardial infarction injury in rats. Int Heart J. 2018;59(2):387-93.
[33]Husain K, Hernandez W, Ansari RA, Ferder L. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J Biol Chem. 2015;6(3):209-17.
[34]Trejo-Moreno C, Méndez-Martínez M3, Zamilpa A, Jiménez-Ferrer E, Perez-Garcia MD, Medina-Campos ON, et al. Cucumis sativus Aqueous Fraction Inhibits Angiotensin II-Induced Inflammation and oxidative stress In vitro. Nutrients. 2018;10(3):E276.
[35]Jackson KL, Marques FZ, Lim K, Davern PJ, Head GA. Circadian differences in the contribution of the brain renin-angiotensin system in genetically hypertensive mice. Front Physiol. 2018;9:231.
[36]Cavka A, Cosic A, Grizelj I, Koller A, Jelaković B, Lombard JH, et al. Effects of AT1 receptor blockade on plasma thromboxane A2 (TXA2) level and skin microcirculation in young healthy women on low salt diet. Kidney Blood Press Res. 2013;37(4-5):432-42.
[37]Tsunoda K, Abe K, Hagino T, Omata K, Misawa S, Imai Y, et al. Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension. Ame J Hypertens. 1993;6(1)28-32.
[38]Crary GS, Swan SK, O'Donnell MP, Kasiske BL, Katz SA, Keane WF. The angiotensin II receptor antagonist losartan reduces blood pressure but not renal injury in obese Zucker rats. J Am Soc Nephrol. 1995;6(4):1295-9.
[2]Macmahon S, Alderman MH, Lindholm LH, Liu L, Sanchez RA, Seedat YK. Blood-pressure-related disease is a global health priority. Am J Hypertend. 2008;21(8):843-4.
[3]Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: Analysis of worldwide data. Lancet. 2005;365(9455):217-23.
[4]Shafei MN, Faramarzi A, Khajavi Rad A, Anaeigoudari A. Crocin prevents acute angiotensin II-induced hypertension in anesthetized rats. Avicenna J Phytomed. 2017;7(4):345-52.
[5]Ferreira JC, Bacurau AV, Evangelista FS, Coelho MA, Oliveira EM, Casarini DE, et al. The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice. Am J Physiol Regul Integ Comp Physiol. 2008;294(1):R26-32.
[6]Mehta PK, Griendling KK. Angiotensin II cell signaling: Physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292(1):C82-97.
[7]Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling KK, et al. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation, contribution to alterations of vasomotor tone. J Clin Invest. 1996;97(8):1916-23.
[8]Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini D, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev. 1993;45(2):205-51.
[9]Cockcroft JR. ACE inhibition in hypertension: Focus on perindopril. Am J Cardiovasc Drugs. 2007;7(5):303-17.
[10]Xu H, Chen Kj. Complementary and alternative medicine: Is it possible to be mainstream?. Chin J Integr Med. 2012;18(6):403-4.
[11]Hosseinzadeh H, Ziaee T, Sadeghi A. The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats. Phytomedicine. 2008;15(6-7):491-5.
[12]José Bagur M, Alonso Salinas GL, Jiménez-Monreal AM, Chaouqi S, Llorens S, Martínez-Tomé M, et al. Saffron: An old medicinal plant and a potential novel functional food. Molecules. 2017;23(1):30.
[13]Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: A comprehensive review. Food Chem Toxicol. 2014;64:65-80.
[14]Hosseinzadeh H, Shamsaie F, Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharmacogn Mag. 2009;5(20):419-24.
[15]Sun Y, Xu HJ, Zhao YX, Wang LZ, Sun LR, Wang Z, et al. Crocin exhibits antitumor effects on human leukemia HL-60 cells in vitro and in vivo. Evid Based Complement Alternat Med. 2013;2013:690164.
[16]Goyal SN, Arora S, Sharma AK, Joshi S, Ray R, Bhatia J, et al. Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats. Phytomedicine. 2010;17(3-4):227-32.
[17]Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res. 2010;24(7):990-4.
[18]Razavi BM, Hosseinzadeh H, Movassaghi AR, Imenshahidi M, Abnous K. Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. Chem Biol Interact. 2013;203(3):547-55.
[19]Ghods R, Gharouni M, Amanlou M, Sharifi N, Ghobadi A, Amin G. Effect of Onopordon acanthium L. as add on antihypertensive therapy in patients with primary hypertension taking losartan: A pilot study. Adv Pharm Bull. 2018;8(1):69-75.
[20]Sever PS, Messerli FH. Hypertension management 2011: Optimal combination therapy. Eur Heart J. 2011;32(20):2499-506.
[21]Gebre AK, Altaye BM, Atey TM, Tuem KB, Berhe DF. Targeting renin–angiotensin system against alzheimer’s disease. Front Pharmacol. 2018;9:440.
[22]Atlas SA. The renin-angiotensin aldosterone system: Pathophysiological role and pharmacologic inhibition. J Manag Care Pharm. 2007;13(8 Supp B):9-20.
[23]Dasgupta C, Zhang L. Angiotensin II receptors and drug discovery in cardiovascular disease. Drug Discov Today. 2011;16(1-2):22-34.
[24]Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, et al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Nati Acad Sci USA. 2006;103(47):17985-90.
[25]Mancini A, Serrano-Díaz J, Nava E, D'alessandro AM, Alonso GL, Carmona M, et al. Crocetin, a carotenoid derived from saffron (Crocus sativus L.), improves acetylcholine-induced vascular relaxation in hypertension. J Vasc Res. 2014;51(5):393-404.
[26]He SY, Qian ZY, Tang FT. Effect of crocin on intracellular calcium concentration in cultured bovine aortic smooth muscle cells. Yao Xue Xue Bao. 2004;39(10):778-81.
[27]Boskabady MH, Shafei MN, Shakiba A, Sang Sefidi H. Effect of aqueous‐ethanol extract from Crocus sativus (saffron) on guinea‐pig isolated heart. Phytother Res. 2008;22(3):330-4.
[28]Kander MC, Cui Y, Liu Z. Gender difference in oxidative stress: A new look at the mechanisms for cardiovascular diseases. J Cell Mol Med. 2017;21(5):1024-32.
[29]Chandra M, Surendra K, Kapoor RK, Ghatak A, Kaur G, Pandey NR, et al. Oxidant stress mechanisms in heart failure. Boll Chim Farm. 2000;139(3)149-52.
[30]Bashar T, Akhter N. Study on oxidative stress and antioxidant level in patients of acute myocardial infarction before and after regular treatment. Bangladesh Med Res Counc Bull. 2014;40(2):79-84.
[31]Zheng YQ, Liu JX, Wang JN, Xu L. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res. 2007;1138:86-94.
[32]Wang Y, Wang Q, Yu W, Du H. Crocin attenuates oxidative stress and myocardial infarction injury in rats. Int Heart J. 2018;59(2):387-93.
[33]Husain K, Hernandez W, Ansari RA, Ferder L. Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. World J Biol Chem. 2015;6(3):209-17.
[34]Trejo-Moreno C, Méndez-Martínez M3, Zamilpa A, Jiménez-Ferrer E, Perez-Garcia MD, Medina-Campos ON, et al. Cucumis sativus Aqueous Fraction Inhibits Angiotensin II-Induced Inflammation and oxidative stress In vitro. Nutrients. 2018;10(3):E276.
[35]Jackson KL, Marques FZ, Lim K, Davern PJ, Head GA. Circadian differences in the contribution of the brain renin-angiotensin system in genetically hypertensive mice. Front Physiol. 2018;9:231.
[36]Cavka A, Cosic A, Grizelj I, Koller A, Jelaković B, Lombard JH, et al. Effects of AT1 receptor blockade on plasma thromboxane A2 (TXA2) level and skin microcirculation in young healthy women on low salt diet. Kidney Blood Press Res. 2013;37(4-5):432-42.
[37]Tsunoda K, Abe K, Hagino T, Omata K, Misawa S, Imai Y, et al. Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension. Ame J Hypertens. 1993;6(1)28-32.
[38]Crary GS, Swan SK, O'Donnell MP, Kasiske BL, Katz SA, Keane WF. The angiotensin II receptor antagonist losartan reduces blood pressure but not renal injury in obese Zucker rats. J Am Soc Nephrol. 1995;6(4):1295-9.