Antihypertensive activity of flowering twigs of Calotropis procera (Ait.) is predominantly mediated through vasorelaxant pathway
Article Sidebar
Main Article Content
Abstract
Objective: To evaluate the crude methanolic (Cp.Cr) and aqueous (Cp.Aq) extracts of Calotropis procera Aiton for acute toxicity and antihypertensive effects, validating its ethnomedicinal use in cardiovascular disorders.
Methods: Phytochemical screening was conducted to determine the chemical constituents of C. procera. Acute toxicity was assessed in BALB/C mice using oral doses of 10, 100, 1000, 1500, and 2000 mg/kg. Vasorelaxant effects were evaluated using rabbit aortic strips pre-contracted with 1 µM norepinephrine and 80 mM potassium chloride (high K⁺) to explore the mechanism of action. Antihypertensive activity was assessed in hypertensive Sprague-Dawley rats at doses of 1 and 10 mg/kg orally, using the tail-cuff method to measure systolic blood pressure.
Results: Phytochemical analysis revealed the presence of flavonoids, saponins, cardiac glycosides, and terpenoids. The extract was non-toxic up to 1500 mg/kg, while a 75% mortality rate was observed at 2000 mg/kg. Both Cp.Cr and Cp.Aq induced dose-dependent relaxation in K⁺ and norepinephrine-induced contractions. The EC₅₀ for Cp.Aq was 0.15 mg/ml for KCl-induced and 0.13 mg/ml for NE-induced contractions. A significant reduction in systolic blood pressure (p<0.05) was observed, particularly with the aqueous fraction of C. procera.
Conclusion: The flowering twigs of C. procera exhibit significant antihypertensive effects, likely mediated through vasorelaxation via inhibition of voltage-gated calcium channels. These findings support its potential use in hypertension management and provide evidence of its safety and pharmacological efficacy.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
Work published in KMUJ is licensed under a
Creative Commons Attribution 4.0 License
Authors are permitted and encouraged to post their work online
(e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
Funding data
References
1. Khairnar A, Bhamare S, Bhamare H. Calotropis procera: an ethnopharmacological update. Adv Res Pharm Bio 2012;2(2):142-56.
2. Ranjit PM, Eswara Rao G, Krishnapriya M, Nagalakshmi V, Silpa P, Anjali M. An overview of phytochemical and pharmacological activities of Calotropis procera. FS J Pharm Res 2012;1(2):18-25.
3. Dwivedi A, Chaturvedi M, Gupta A, Argal A. Medicinal utility of Calotropis procera (Ait.) R. Br. as used by natives of village Sanwer of Indore District, Madhya Pradesh. Int J Pharm Life Sci 2010;1(3):188-90.
4. Paul A, Kumar A. Review on pharmocological properties of aaka (Calotropis procera). Int J Econ Plants 2018;5(3):157-62.
5. Iqbal Z, Lateef M, Jabbar A, Muhammad G, Khan MN. Anthelmintic activity of Calotropis procera (Ait.) Ait. F. flowers in sheep. J Ethnopharmacol 2005;102(2):256-61. https://doi.org/10.1016/j.jep.2005.06.022
6. Mascolo N, Sharma R, Jain S, Capasso F. Ethnopharmacology of Calotropis procera flowers. J Ethnopharmacol 1988;22(2):211-21. https://doi.org/10.1016/0378-8741(88)90129-8
7. Ramachandra Setty S, Quereshi AA, Viswanath Swamy A, Patil T, Prakash T, Prabhu K, et al. Hepatoprotective activity of Calotropis procera flowers against paracetamol-induced hepatic injury in rats. Fitoterapia 2007;78(7-8):451-4. https://doi.org/10.1016/j.fitote.2006.11.022
8. Ahmed M, Khan R, Shahzaib S, Khan A, Zaif A, Ahmed W. Antifungal, antioxidant and antibacterial activities of Calotropis procera. Int J Biosci 2014;5:75-80.
9. Kamath J, Rana A. Pharmacological activities of ethanolic extract of Calotropis procera roots. Indian Drugs 2003;40(5):292-5.
10. Atawodi SE-O, Olowoniyi OD, Daikwo MA. Ethnobotanical survey of some plants used for the management of hypertension in the Igala speaking area of Kogi State, Nigeria. Ann Res Rev Biol 2014:4535-43. https://doi.org/10.9734/ARRB/2014/8633
11. Evans WC. Trease and Evans' Pharmacognosy E-Book: Elsevier Health Sciences; 2009. ISBN: 9780702048838
12. Ali N, Sultana U, Shah SWA, Nabi M, Shah I, Ahmed G. Acute toxicity and analgesic activity of crude flavonoids of Achillea Wilhelmsii and Teucrium Stocksianum. Khyber Med Univ J 2016;8(1):7-11.
13. Ali N, Ahmed G, Shah SWA, Shah I, Ghias M, Khan I. Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis. BMC Complement Altern Med 2011;11(1):99. https://doi.org/10.1186/1472-6882-11-99
14. Cheng Y-W, Kang J-J. Mechanism of vasorelaxation of thoracic aorta caused by xanthone. Eur J Pharmacol 1997;336(1):23-8. https://doi.org/10.1016/S0014-2999(97)01224-7
15. Li J, Li W-Q, Yao Y. Vasorelaxation Effect of Estrone Derivate EA204 in Rabbit Aorta. Scientifica 2016:2016:7405797. https://doi.org/10.1155/2016/7405797
16. Karaki H, Ozaki H, Hori M, Mitsui-Saito M, Amano K-I, Harada K-I, et al. Calcium movements, distribution, and functions in smooth muscle. Pharmacol Rev 1997;49(2):157-230.
17. Musha S, Watanabe M, Ishida Y, Kato S, Konishi M, Tomoda A. A phenoxazine compound, 2-amino-4, 4α-dihydro-4α-7-dimethyl-3H-phenoxazine-3-one reverses the phenylephrine or high-K+ induced contraction of smooth muscles in rat aorta and guinea pig tenia cecum. Biol Pharm Bull 2005;28(8):1521-3. https://doi.org/10.1248/bpb.28.1521
18. Cauvin C, Saida K, van Breemen C. Extracellular Ca2+ dependence and diltiazem inhibition of contraction in rabbit conduit arteries and mesenteric resistance vessels. Blood Vessels 1984;21(1):23-31. https://doi.org/10.1159/000158491
19. Ali N, Begum R, Faisal MS, Khan A, Nabi M, Shehzadi G, et al. Current statins show calcium channel blocking activity through voltage gated channels. BMC Pharmacol Toxicol 2016;17(1):43. https://doi.org/10.1186/s40360-016-0086-5
20. Shahid A, Khan DA, Aati HY, Sherif AE, Ovatlarnporn C, Hussain M, et al. Chemical profiling and biological activities of Dipterygium glaucum Decne.: an in-vivo, in-vitro and in-silico evaluation. South Afr J Bot 2023;160:715-30. https://doi.org/10.1016/j.sajb.2023.07.033
21. Rao H, Ahmad S, Aati HY, Basit A, Ahmad I, Ghalloo BA, et al. Phytochemical screening, biological evaluation, and molecular docking studies of aerial parts of Trigonella hamosa (branched Fenugreek). Arab J Chem 2023;16(7):104795. https://doi.org/10.1016/j.arabjc.2023.104795
22. Lei M, Wang L, Olatunde OO, Singh S, Ovatlarnporn C, Basit A, et al. UPLC–ESI–QTOF–MS profiling, antioxidant, antidiabetic, antibacterial, anti-inflammatory, antiproliferative activities and in silico molecular docking analysis of Barleria strigosa. Chem Biol Technol Agric 2023;10(1):73. https://doi.org/10.1186/s40538-023-00451-2
23. Basit A, Ahmad S, Sherif AE, Aati HY, Ovatlarnporn C, Khan MA, et al. New mechanistic insights on Justicia vahlii Roth: UPLC-Q-TOF-MS and GC–MS based metabolomics, in-vivo, in-silico toxicological, antioxidant based anti-inflammatory and enzyme inhibition evaluation. Arab J Chem 2022;15(10):104135. https://doi.org/10.1016/j.arabjc.2022.104135
24. Basit A, Ahmad S, Ovatlarnporn C, Arshad MA, Saleem MF, Khurshid U, et al. Unrivalled insight into possible biopharmaceutical application of Justicia Vahlii Roth. (acanthaceae): chemodiversity, in vitro bioactivities, and computational analysis. Chem Biodiversity 2024;21(12):e202401432. https://doi.org/10.1002/cbdv.202401432
25. Gul H, Hussain A, Javaid F, Khan KU, Basit A, Arafat M, et al. Novel insights into the anti-asthmatic effect of Raphanus sativus L. (Raphani Semen): targeting immune cells, inflammatory pathways and oxidative stress markers. J Ethnopharmacol 2024;325:117851. https://doi.org/10.1016/j.jep.2024.117851
26. Gilani AH, Khan A-u, Jabeen Q, Subhan F, Ghafar R. Antispasmodic and blood pressure lowering effects of Valeriana wallichii are mediated through K+ channel activation. J Ethnopharmacol 2005;100(3):347-52. https://doi.org/10.1016/j.jep.2005.05.010
27. Ali N, Ali W, Ullah A, Ahmad S, Alsaiari AA, Almehmadi M, et al. Atorvastatin and Fluvastatin potentiate blood pressure lowering effect of Amlodipine through vasorelaxant phenomenon. Medicina 2023;59(6):1023. https://doi.org/10.3390/medicina59061023
28. Ali W, Ali N, Ullah A, Rahman SU, Ahmad S. Pitavastatin and Lovastatin exhibit calcium channel blocking activity which potentiate vasorelaxant effects of amlodipine: a new futuristic dimension in statin’s pleiotropy. Medicina 2023;59(10):1805. https://doi.org/10.3390/medicina59101805
29. Lorenz JN. A practical guide to evaluating cardiovascular, renal, and pulmonary function in mice. Am J Physiol Regul Integr Comp Physiol 2002;282(6):R1565-R82. https://doi.org/10.1152/ajpregu.00759.2001
30. Chan SS-K, Choi AO-K, Jones RL, Lin G. Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta. Eur J Pharmacol 2006;537(1):111-7. https://doi.org/10.1016/j.ejphar.2006.03.015