EVALUATION OF ANTI-HYPERTROPHIC POTENTIAL OF PIPER BETLE IN ISOPROTERENOL-INDUCED CARDIAC HYPERTROPHIC RAT MODELS
Objective: The objective of this study was to evaluate the anti-hypertrophic potential of the combination extract (chloroform, methanol, and ethyl acetate) of Piper betle in cardiac hypertrophic rat models.
Methods: Isoproterenol (ISO) (10 mg/kg b. w., i.p., 7 days) was used to induce cardiac hypertrophy in male albino Wistar rats and simultaneously treated with the combination extract of P. betle (50 mg/kg b. w., oral, 7 days) and the standard drug losartan (50 mg/kg b. w., oral, 7 days) as reference. At the end of seventh day the biochemical estimations of glucose, protein, cholesterol, triglycerides, cardiac marker enzymes (SGOT, SGPT and LDH) and enzymic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) were performed in the serum along with the targets of the study namely calcium and phosphorus. Heart tissues were subjected to histopathological analysis. All biochemical assays were statistically verified.
Results: The status of cardiac hypertrophy was indicated by the increased heart weight (HW)/body weight (BW) ratio. The biochemical assays showed significant (p<0.05) increase in the levels of glucose, protein, and cholesterol and in the cardiac marker enzymes such as SGOT, SGPT, and LDH, whereas significant decrease in the serum calcium and phosphorus along with antioxidants were seen in the ISO-induced rats and these levels were restored to normal values by the treatment with P. betle.
Conclusion: The combination extract of P. betle showed effect upon calcium and phosphorus levels besides reversing the other impacts of isoproterenol (β-adrenergic hypersignaling events) probably due to phytoconstituents of the plant which are hypothesized to be efficiently extracted in combination of organic solvents, and thus, these results indicate that the combination extract of P. betle possesses cardioprotective (anti-hypertrophic) effect.
2. Rothermel BA, Berenji K, Tannous P, Kutschke W, Dey A, Nolan B, et al. Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure. Physiol Genomics 2005;23:18-27.
3. Rohini A, Agarwal N, Chandrasekar NJM aand Sara SVU. Evaluation of cardioprotective effect of Zingiber officinale in experimental animals. IJCPR 2013;4:1-9.
4. Rekha VP, Kollipara M, Gupta S, Bharath Y, Pulicherla KK. A review on Piper betle L.: Nature’s promising medicinal reservoir. Am J Ethnomed 2014;1:276-89.
5. Patra B, Das MT, Dey SK. A review on Piper betle L. J Med Plants Stud 2016;4:185-92.
6. Saini S, Dhiman A, Nanda S. Pharmacognostical and phytochemical studies of Piper betle Linn Leaf. Int J Pharm Pharm Sci 2016;8:222-6.
7. Chakraborty D, Shah B. Anti-microbial, antioxidative and anti-hemolytic activity of Piper betle extracts. Int J Pharm Pharm Sci 2011;3:192-9.
8. Murali B, Upadhyaya UM, Goyal RK. Effect of chronic treatment with Enicostemma littorale in non-insulin-dependent diabetic (NIDDM) rats. J Ethnopharmacol 2002;81:199-204.
9. Gracelin SH, De Britto JA, Benjamin P, Kumar RJ. Qualitative and quantitative analysis of phytochemicals in five Pteris species. Int J Pharm Pharm Sci 2012;5:105-7.
10. Chang ST, Wu JH, Wang SY, Kang PL, Yang NS, Shyur LF, et al. Antioxidant activity of extracts from Acacia confusa bark and heartwood. J Agric Food Chem 2001;49:3420-4.
11. Rai S, Wahile A, Mukherjee K, Saha BP, Mukherjee PK. Antioxidant activity of Nelumbo nucifera (sacred lotus) seeds. J Ethnopharmacol 2006;104:322-7.
12. Zhang S, Tang F, Yang Y, Lu M, Luan A, Zhang J, et al. Astragaloside IV protects against isoproterenol-induced cardiac hypertrophy by regulating NF-?B/PGC-1? signaling mediated energy biosynthesis. PLoS One 2015;10:e0118759.
13. Jordi GG, Guash E, Benito B, Brugada J, Nattel S, Mont L and Mollar AS. Losartan prevents heart fibrosis induced by long-term intensive exercise in an animal model. PLoS One 2013;8:e55427.
14. Lien LT, Tho NT, Ha DM, Hang PL, Nghia PT, Thang ND, et al. Influence of phytochemicals in Piper betle Linn leaf extract on wound healing. Burns Trauma 2015;3:23.
15. Doss VA, Parthibhan J, Kuberapandian D. Evaluation of anti-hypertrophic potential of Camellia sinensis in isoproterenol induced cardiac hypertrophy. Int J Pharm Pharm Sci 2018;10:119-23.
16. Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130 2.
17. Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47:389 94.
18. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG, et al. Selenium: Biochemical role as a component of glutathione peroxidase. Science 1973;179:588-90.
19. Al-Rasheed NM, Al-Oteibi MM, Al-Manee RZ, Al-Shareef SA, Al-Rasheed NM, Hasan IH, et al. Simvastatin prevents isoproterenol- induced cardiac hypertrophy through modulation of the JAK/STAT pathway. Drug Des Devel Ther 2015;9:3217-29.
20. Snedecor GW, Cochran WG. Shortcut and Non-parametric Methods. In: Statistical Methods. New York: Oxford and IBH; 1986.
21. Njoku PC, Akumefula MI. Pak J Nutr 2007;6:613-15.
22. James DB, Abu EA, Wurochekk AU, Orji GN. Phytochemical and antimicrobial investigation of the aqueous and methanolic extracts of Ximenia Americana. J Med Sci 2007;7:284-8.
23. Rathee JS, Patro BS, Mula S, Gamre S, Chattopadhyay S. Antioxidant activity of piper betel leaf extract and its constituents. J Agric Food Chem 2006;54:9046-54.
24. Nazira A, Kanthimani MS, Aziz AA. Piper betle shows antioxidant activities, inhibits MCF-7 cell proliferation and increases activities of catalase and superoxide dismutase. BMC Complement Altern Med 2012;12:220.
25. Ennis IL, Escudero EM, Console GM, Camihort G, Dumm CG, Seidler RW, et al. Regression of isoproterenol-induced cardiac hypertrophy by na+/H+ exchanger inhibition. Hypertension 2003;41:1324-9.
26. Doss VA, Kuberapandian D. Evaluation of anti-hypertrophic potential of Enicostemma littorale blume on isoproterenol induced cardiac hypertrophy. Indian J Clin Biochem 2019. Avaliable online: https://doi.org/10.1007/s12291-019-0814-x
27. Patel VB, Vacek JL, Graves L, Bhattacharya RK. Calcium affects on vascular endpoints. Nutr Metab (Lond) 2012;9:24.
28. Dhingra R, Gona P, Benjamin EJ, Wang TJ, Aragam J, D’Agostino RB, et al. Relations of serum phosphorus levels to echocardiographic left ventricular mass and incidence of heart failure in the community. Eur J Heart Fail 2010;12:812-8.
29. Tomasello S. Secondary hyperparathyroidism and chronic kidney disease. Diabetes Spectrum 2008;21:19-25.
30. Saxena R, Wijnhoud AD, Man in ‘t Veld AJ, van den Meiracker AH, Boomsma F, Przybelski RJ, et al. Effect of diaspirin cross-linked hemoglobin on endothelin-1 and blood pressure in acute ischemic stroke in man. J Hypertens 1998;16:1459-65.
31. Ali MS, Mudagal MP, Goli D. Cardioprotective effect of tetrahydrocurcumin and rutin on lipid peroxides and antioxidants in experimentally induced myocardial infarction in rats. Pharmazie 2009;64:132-6.
32. Padma VV, Poornima P, Prakash C, Bhavani R. Oral treatment with gallicnacid and quercetin alleviates lindane-induced cardiotoxicity in rats. Can J Physiol Pharmacol 2013;91:134-40.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.