Nigella Sativa AQUEOUS AND HYDRO-METHANOL EXTRACTS ACT AS A NOVEL BLOCKER FOR ANGIOTENSIN II RECEPTOR TYPE I

  • IHSAN HUSAIN MOHAMMED ALI Lecturer, Department of Medical Physiology. & Pharmacology, College of Medicine, University of Duhok, Kurdistan Region, Iraq.
  • QASIM HASSO ABDULLAH Professor, Department of Medical Physio. & Pharma, University of Duhok, Kurdistan Region, Iraq.
  • OMAR ABDUL MAJEED AL-HABIB Professor, Department of Biology, College of Science, University of Zakho, Kurdistan Region, Iraq,
Keywords: Angiotensin II Type 1 Receptor, Anti-Hypertensive, Aqueous Extract, Hydromethanol, Nigella Sativa

Abstract

https://doi.org/10.31386/dmj.2020.14.2.8

Background: It is well known that Nigella sativa seeds have been widely used in folk medicine for the treatment of cardiovascular diseases. Little is known, however, about their effect on angiotensin II receptor type I. Studying of such impact will be valuable in producing herbal medicines with much less side effects compared to conventional drugs.

Objective: The aim of the current research was to study the blocking effect of hydro-methanolic (NS.HM) and aqueous (NS.Aq) extracts of Nigella sativa on angiotensin II (Ang II) receptor type I (AT1) in isolated rat's aorta.

Materials and Methods: Seed's powder was soaked in 50% hydromethanol and distilled water separately for 48 hrs, then filtered through Whatman filter papers. The solvents were evaporated to yield the crude extracts (NS.HM and NS.Aq). The effect of different concentrations (1, 2, 3 & 4 mg/ml) of NS.HM and NS.Aq extracts on isolated rat's aorta contracted with various doses of Ang II (0.3, 1.0, 3.0, 10, 30 & 100 µM) were evaluated.

Results: NS.HM at concentrations 3 and 4 mg/ml, caused a very high significant (P< 0.001) inhibitory effect on the dose-response curves (DRCs) in aortic rings at doses 3 and 10 µM of Ang II as compared to the control, and a highly significant (P< 0.01) inhibition at doses one µM (for 3 mg/ml), and 1 and 30 µM (for 4 mg/ml). Furthermore, NS.HM at concentrations 1 and 2 mg/ml did not produce any significant right shifting. On the other hand, NS.Aq extract at concentration 4 mg/ml caused a very high significant (P< 0.001) right shifting DRC at doses 3 and 10 µM, and highly significant (P< 0.01) shifting at 30 µM of Ang II. Besides, significant right shifting (P< 0.05) was observed in the DRC in the presence of the extract at dose one µM as compared to the control. Nevertheless, no right shifting in the DRC of Ang II at concentrations 1, 2, and 3 mg/ml of NS.Aq was noticed.

Conclusions: We conclude that Both NS.HM and NS.Aq extracts have an anti-hypertensive effect through blocking the AT1 receptors, although NS.HM extract is more potent in blocking effect on AT1R than NS.Aq. In addition, the anti-hypertensive effect of both NS.HM and NS.Aq extracts on the aorta are concentration-dependent.

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References

1. Musharraf H, Arman S. Prophetic medicine is the cheapest, safest and the best remedy in the prevention and treatment of hypertension (high blood pressure) – a mini review. International Journal of Molecular Biology. 2018; 3(5):245‒250.
2. Ahmad A, Husain A, Mujeeb M, Alam Khan S, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013; 3(5): 337-352.
3. Kamal A, Ahmad I. Phytochemical studies of different phases of germination of nigella sativa linn – a medicinally important plant. International Journal of Pharmacy and Pharmaceutical Sciences. 2014; 6 (4): 0975-1491.
4. Matsusaka T, Ichikawa I. Biological Functions of Angiotensin and Its Receptors. Annual Review of Physiology. 1997; 59: 395-412.
5. Young BM, Nguyen E, Chedrawe MA, Rainey JK, Dupré DJ. Differential Contribution of Transmembrane Domains IV, V, VI, and VII to Human Angiotensin II Type 1 Receptor Homomer Formation. J Biol Chem. 2017; 292(8): 3341-3350.
6. Ghorayeb NE, Bourdeau I, Lacroix A. Role of ACTH and Other Hormones in the Regulation of Aldosterone Production in Primary Aldosteronism. Frontiers in Endocrinology. 2016; 7: 72.
7. Corrêa TD, Takala J, Jakob SM. Angiotensin II in septic shock. Critical Care. 2015; 19: 98.
8. Ainscough FX, Drinkhill J, Sedo A, Turner A, Brooke A, Balmforth J, et al. Angiotensin II type-1 receptor activation in the adult heart causes blood pressure-independent hypertrophy and cardiac dysfunction. European Society of Cardiology. 2009; 81: 592–600.
9. Tangi K, Israili Z, Lyoussi B. Vasorelaxant effect of essential oil isolated from Nigella sativa L. seeds in rat aorta: Proposed mechanism. Pak. J. Pharm. Science. 2016; 29(1):1-8.
10. Santos M, Moreira F, Fraga B, Sousa D, Bonjardim L, Junior L. Cardiovascular effects of monoterpenes. Brazilian Journal of Pharmacognosy.2011; 21 (4): 764-771.
11. Niazmand S, Fereidouni E, Mahmoudabady M, Mousavi S. Endothelium-Independent Vasorelaxant Effects of Hydroalcoholic Extract from Nigella sativa Seed in Rat Aorta: The Roles of Ca2+ and K+ Channels. BioMed Research International. 2014; Article ID 247054, 7 pages.
12. Boskabady MH, Shafei M, Parsaee H. Effects of aqueous and macerated extracts from Nigella sativa on guinea pig isolated heart activity. Pharmazie. 2005; 60: 943-8.
13. Shafei MN, Boskabady MH, Parsaee H. Effect of aqueous extract from Nigella sativa L. on guinea pig isolated heart. Indian J Exp Biol. 2005; 43:635-9.
14. Khalaf M. Relaxant effect of nitric oxide & hydrogen sulfide on isolated trachea in male albino rats. M.Sc. Thesis 2014. University of Zakho. College of Science.
15. Naji L. Physiological Effects Of Some Punica Granatum Fractions On Contractility Of Isolated Aorta In Female Albino Rats. M.Sc. Thesis 2016. University of Zakho. College of Science.
16. Bregeon J, Loirand G, Pacaud P, Derkinderen M. Angiotensin II induces RhoA activation through SHP2-dependent dephosphorylation of the RhoGAP p190A in vascular smooth muscle cells. Am J Physiol Cell Physio. 2009; 297: C1062–C1070.
17. Kawai T, Forrester S, O'Brien S, Baggett A, Rizzo V, Eguchi S. AT1 receptor signaling pathways in the cardiovascular system. Pharmacol Res. 2017; 125(Pt A): 4–13.
18. Mustafa C. The Role of Bradykinin, Nitric Oxide, and Protein Kinase A in Angiotensin II Type-2 Receptor Induces Vasodilation. PhD Thesis. 2018. University of Zakho. College of Science. P. 54.
19. Sen S, Kanter M, Ustundag S, Aktas C, Dogutan H, Yalcin O. Effect of Angiotensin-Converting Enzyme Inhibition and Angiotensin II Type 1 Receptor Blockade on Streptozotocin-Induced Diabetic Nephropathy. Renal Failure. 2008; 30: 1023-33.
20. Singh K, Karnik S. Angiotensin Receptors: Structure, Function, Signaling and Clinical Applications. J Cell Signal. 2016; 1(2): doi:10.4172/jcs.1000111.
21. Allen A, Zhuo J, Mendelsohn F. Localization and function of angiotensin AT1 receptors. Am J Hypertens. 2000; 13: 31S-38S.
22. Wettschureck N, Offermanns S. Mammalian G Proteins and Their Cell Type Specific Functions. Physiol Rev. 2005; 85: 1159–1204.
23. Mehta PK, Griendling KK. Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. American Journal of Physiology - Cell Physiology. 2007; 292(1):C82–C97.
24. Nguyen A, Touyz RM. Cell signaling of angiotensin II on vascular tone: novel mechanisms. Curr Hypertens Rep. 2011;13(2):122–128.
25. Duarte J, Vizcaino FP, Utrilla P, Jimenez J, Tamargo J, Zarzuelo A. Vasodilatory Effect of Flavonoids in Rat Aortic Smooth Muscle. Structure-Activity Relation. Gen. Pharmac. 1993; 24(4): 857-862.
26. Szentandrássy N, Szigeti G, Szegedi C, Sárközi S, Magyar J, Bányász T, et al. Effect of thymol on calcium handling in mammalian ventricular myocardium. Life Sci. 2004; 74: 909-921.
27. Shoshan V, Campbell KP, MacLennan DH, Frodis W, Britt BA, et al. quercetin inhibits Ca2+ uptake but not Ca2+ release by sarcoplasmic reticulum in skinned muscle fibers. Proc. hath. Acad. Sci. 1980; 77: 4435-4438.
28. Nishino H, Naito A, Iwashima A, Tanaka KI, Matsuura T, Fujiki H, et al. Interaction between quercetin and Ca2+-calmodulin complex: possible mechanism for anti-tumor promoting action of the flavonoid. Jpn. J. Cancer Res. 1984; 75: 311-316.
29. Magyar J, Szentandrássy N, Bányász T, Fülöp L, Varró A, Nánási PP, et al. Effects of terpenoid phenol derivatives on calcium current in canine and human ventricular cardiomyocytes. Eur J Pharmacol. 2004; 487: 29-36.
30. Nishijima H, Uchida R, Kameyama K, Kawakami N, Onkubo T, Kitamura K. Mechanisms mediating the vasorelaxing action of eugenol, a pungent oil, on rabbit arterial tissue. Jpn. J. Pharamcol. 1999; 79: 327-334.
Published
2021-01-08
How to Cite
HUSAIN MOHAMMED ALI, I., HASSO ABDULLAH, Q., & ABDUL MAJEED AL-HABIB, O. (2021). Nigella Sativa AQUEOUS AND HYDRO-METHANOL EXTRACTS ACT AS A NOVEL BLOCKER FOR ANGIOTENSIN II RECEPTOR TYPE I. Duhok Medical Journal, 14(2), 73-85. Retrieved from https://dmj.uod.ac/index.php/dmj/article/view/136