Diosgenin Ameliorates Cardiac Function following Myocardial Ischemia Through Angiogenic and Anti-Fibrotic Properties; An Experimental Study
Archives of Academic Emergency Medicine,
Vol. 13 No. 1 (2025),
6 September 2025
,
Page e40
https://doi.org/10.22037/aaemj.v13i1.2483
Abstract
Introduction: Angiogenesis through restoration of blood supply to the ischemic myocardium is a pivotal process that contributes to cardiac repair and leads to improvement of myocardial function. This study was conducted to evaluate cardioprotective effects of Diosgenin against myocardial infarction (MI) with focus on angiogenesis, myocardial fibrosis, and oxidative stress.
Methods: 4 groups of male Wistar rats were considered for this study: (1) sham, (2) MI, (3) MI+Vehicle and (4) MI+Diosgenin. MI model was created by occluding left anterior descending (LAD) artery for 30 minutes and reperfusion was established for 14 days by opening this artery. Diosgenin (50 mg/kg) was given orally to the rats for 21 days (from 7 days before MI induction until the end of the 14-day reperfusion period). Cardiac injury markers including troponin I, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH) were measured using enzyme-linked immunosorbent assay (ELISA), same as cardiac stress oxidative markers (superoxide dismutase (SOD), Malondialdehyde (MDA), reduced glutathione (GSH)). Echocardiography was used to measure heart function parameters and myocardial fibrosis was assessed via a specific tissue staining named Masson׳s trichrome. Blood vessel staining kit was used to assess left ventricular angiogenesis.
Results: Ischemia-reperfusion injury increased serum levels of troponin I, CK-MB and LDH, as well as cardiac malondialdehyde (MDA) and myocardial fibrosis. MI also decreased myocardial function (Ejection fraction (EF)% and Fractional shortening (FS)%) and Diosgenin treatment reversed these parameters. Capillary density as marker of angiogenesis significantly increased in all of MI groups. However, development of angiogenesis was significantly higher in Diosgenin group compared with MI group.
Conclusion: Diosgenin exerts cardioprotective effects against ischemia-reperfusion injury by strengthening cardiac antioxidant defense and reducing deposition of collagen fibers. It seems that the strengthening of angiogenesis in heart tissue is one of the main mechanisms of Diosgenin to increase the heart's resistance against ischemia.
- Myocardial infarction
- Reperfusion injury
- Angiogenesis
- Diosgenin
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References
Pletsch-Borba L, Grafetstätter M, Hüsing A, Maldonado SG, Kloss M, Groß M-L, et al. Biomarkers of vascular injury in relation to myocardial infarction risk: A population-based study. Sci Rep. 2019; 9(1):3004.
Choopani S, Imani A, Faghihi M, Askari S, Edalatyzadeh Z. Chronic Sleep Deprevation And Ventricular Arrhythmias: Effect Of Symphatic Nervous System. J Cell Mol Anesth. 2016;1(2):e149508.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129(3):399-410.
Janicki JS, Brower GL, Gardner JD, Chancey AL, Stewart JA. The dynamic interaction between matrix metalloproteinase activity and adverse myocardial remodeling. Heart fail rev. 2004; 9(1):33-42.
Rakhshan K, Azizi Y, Naderi N, Afousi AG, Aboutaleb N. ELABELA (ELA) peptide exerts cardioprotection against myocardial infarction by targeting oxidative stress and the improvement of heart function. Int J Pept Res Ther. 2019;25(2):613-21.
Saporito F, Baugh LM, Rossi S, Bonferoni MC, Perotti C, Sandri G, et al. In Situ Gelling Scaffolds Loaded with Platelet Growth Factors to Improve Cardiomyocyte Survival after Ischemia. Acs biomater sci eng. 2018; 5(1):329-38.
Cheng Y, Jiang S, Hu R, Lv L. Potential mechanism for endothelial progenitor cell therapy in acute myocardial infarction: Activation of VEGF-PI3K/Akte-NOS pathway. Ann Clin Lab Sci. 2013; 43(4):395-401.
Jin P, Li T, Li X, Shen X, Zhao Y. Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice. Exp Ther Med. 2016; 11(6):2163-70.
Swieczkowski D, Mogielnicki M, Cwalina N, Zuk G, Pisowodzka I, Ciecwierz D, et al. Medication adherence in patients after percutaneous coronary intervention due to acute myocardial infarction: From research to clinical implications. Cardiol J. 2016; 23(5):483-90.
Souri F, Rakhshan K, Erfani S, Azizi Y, Maleki SN, Aboutaleb N. Natural lavender oil (Lavandula angustifolia) exerts cardioprotective effects against myocardial infarction by targeting inflammation and oxidative stress. Inflammopharmacology. 2019;27(4):799-807.
Lee DJ, Cavasin MA, Rocker AJ, Soranno DE, Meng X, Shandas R, et al. An injectable sulfonated reversible thermal gel for therapeutic angiogenesis to protect cardiac function after a myocardial infarction. J Biol Eng. 2019; 13(1):6.
Hirai S, Uemura T, Mizoguchi N, Lee JY, Taketani K, Nakano Y, et al. Diosgenin attenuates inflammatory changes in the interaction between adipocytes and macrophages. Mol Nutr Food Res. 2010; 54(6):797-804.
Moalic S, Liagre B, Corbière C, Bianchi A, Dauça M, Bordji K, et al. A plant steroid, diosgenin, induces apoptosis, cell cycle arrest and COX activity in osteosarcoma cells. FEBS letters. 2001;506(3):225-30.
Sethi G, Shanmugam MK, Warrier S, Merarchi M, Arfuso F, Kumar AP, et al. Pro-apoptotic and anti-cancer properties of diosgenin: A comprehensive and critical review. Nutrients. 2018;10(5):645.
Chen C-T, Wang Z-H, Hsu C-C, Lin H-H, Chen J-H. In vivo protective effects of diosgenin against doxorubicin-induced cardiotoxicity. Nutrients. 2015;7(6):4938-54.
McAnuff MA, Omoruyi FO, Morrison EY, Asemota HN. Plasma and liver lipid distributions in streptozotocin-induced diabetic rats fed sapogenin extract of the Jamaican bitter yam (Dioscorea polygonoides). Nutr Res. 2002; 22(12):1427-34.
McAnuff MA, Harding WW, Omoruyi FO, Jacobs H, Morrison EY, Asemota HN. Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food Chem Toxicol. 2005;43(11):1667-72.
Esfandiarei M, Lam JT, Yazdi SA, Kariminia A, Dorado JN, Kuzeljevic B, et al. Diosgenin modulates vascular smooth muscle cell function by regulating cell viability, migration, and calcium homeostasis. J Pharmacol Exp Ther. 2011;336(3):925-39.
Manivannan J, Shanthakumar J, Silambarasan T, Balamurugan E, Raja B. Diosgenin, a steroidal saponin, prevents hypertension, cardiac remodeling and oxidative stress in adenine induced chronic renal failure rats. RSC Adv. 2015; 5(25):19337-44.
Pari L, Monisha P, Jalaludeen AM. Beneficial role of diosgenin on oxidative stress in aorta of streptozotocin induced diabetic rats. Eur J Pharmacol. 2012;691(1-3):143-50.
Manivannan J, Barathkumar T, Sivasubramanian J, Arunagiri P, Raja B, Balamurugan E. Diosgenin attenuates vascular calcification in chronic renal failure rats. Mol Cell Biochem. 2013;378(1-2):9-18.
Puleo PR, Guadagno PA, Roberts R, Scheel MV, Marian AJ, Churchill D, et al. Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB. Circulation. 1990;82(3):759-64.
Salimeh A, Mohammadi M, Mohaddes G, Badalzadeh R. Protective effect of diosgenin and exercise training on biochemical and ECG alteration in isoproterenol-induced myocardial infarction in rats. Iran J Basic Med Sci. 2011; 14(3): 264-274.
Jayachandran K, Vasanthi HR, Rajamanickam G. Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction. Mol Cell Biochem. 2009;327(1-2):203-10.
Oyelaja-Akinsipo OB, Dare EO, Katare DP. Protective role of diosgenin against hyperglycaemia-mediated cerebral ischemic brain injury in zebrafish model of type II diabetes mellitus. Heliyon. 2020;6(1):e03296.
Wang H-W, Liu H-J, Cao H, Qiao Z-Y, Xu Y-W. Diosgenin protects rats from myocardial inflammatory injury induced by ischemia-reperfusion. Medical science monitor: Int J Exp Clin Res. 2018; 24:246-253.
Ebrahimi H, Badalzadeh R, Mohammadi M, Yousefi B. Diosgenin attenuates inflammatory response induced by myocardial reperfusion injury: role of mitochondrial ATP-sensitive potassium channels. J Physiol Biochem. 2014;70(2):425-32.
Zhou HT, Yu XF, Zhou GM. Diosgenin inhibits angiotensin II-induced extracellular matrix remodeling in cardiac fibroblasts through regulating the TGF‑β1/Smad3 signaling pathway. Mol Med Rep. 2017; 15(5):2823-8.
Badimon L, Borrell M. Microvasculature recovery by angiogenesis after myocardial infarction. Curr Pharm Des. 2018;24(25):2967-73.
Ferrara N, Gerber H-P. The role of vascular endothelial growth factor in angiogenesis. Acta haematol. 2001;106(4):148-56.
Yen ML, Su JL, Chien CL, Tseng KW, Yang CY, Chen WF, et al. Diosgenin induces hypoxia-inducible factor-1 activation and angiogenesis through estrogen receptor-related phosphatidylinositol 3-kinase/Akt and p38 mitogen-activated protein kinase pathways in osteoblasts. Mol pharmacol. 2005;68(4):1061-73.
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