Cleistopholis patens root bark extract exerts cardioprotective effect against doxorubicin-induced myocardial toxicity in rats.

Abstract

Background: Myocardial Infarction still persists as the most prevalent cardiovascular disease and is a top cause of morbidity and mortality in doxorubicin treated cancer patients. This study evaluated the prophylactic effect of the ethanol root bark extract of Cleistopholis patens (ERBECP) against doxorubicin-induced myocardial infarction in wistar rats. Extraction, preliminary phytochemical analysis, acute toxicity study and body weight (b.w.) of ERBECP were achieved using standard methods. Phyto-constituents in ERBECP were indentified using Gas Chromatography-Mass Spectrometry (GC-MS) technique. Thirty (30) male albino Wistar rats of average b.w. ranging between 100 and 130 g were divided into six groups of five rats each. Groups I, II and III served as normal, doxorubicin (DOX) and standard (Vasoprin 150 mg/kg b.w) controls respectively, while groups IV, V and VI were orally pre-treated with the extract (200, 400 and 600 mg/kgb.w) for two weeks prior to intraperitoneal induction of cardiotoxicity with DOX (20 mg/kg bw) on day 14.

Results: Disturbances in serum cardiac function bio-markers such as; Cardiac Troponin-I (CTnI), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT). Lipid profile markers such as; Total cholesterol (TC), Triacylglycerol (TAG), Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL). Oxidative stress markers such as; Malondialdehyde (MDA), Superoxide Dismutase (SOD), Catalase (CAT), Glutathione (GSH) confirmed the induction of myocardial infarction. Histological assessment of heart tissues was performed to validate biochemical results. The GC-MS analysis of ERBECP identified a total of 69 compounds. Safety profile of the aqueous extract was safe for the animals up to the highest dose of 5000 mg/kg b.w. Pre-treatment of DOX group with ERBECP could significantly increase the b.w. compared to the DOX-treated group during the experimental period of 2 weeks. There were significant (p < 0.05) alterations in the levels of CTnI, CK, LDH, AST, ALT and lipid profile indices in the DOX control rats. Also, significant (p < 0.05) increase was observed in MDA and decrease in SOD, CAT and GSH in the DOX control rats. However, administration of the extract significantly (p < 0.05) normalized these alterations and reversed the architectural changes in the heart. The 69 compounds were screened against the target protein (CBR1); we identified seven hits based on the docking score and interactions with the active site residues. All the C. patens constituents had MW (g/mol) less than 500, HBA < 10 and HBD not more than 5. Apart, 9-Octadecenoic acid (Z)-, 2,3-dihydroxy propyl ester and Estra-1,3,5(10)-trien-17. beta. -ol, all the constituents had LD₅₀ lower than 2000 mg/kg.

Conclusions: The findings reveals ERBECP demonstrated promising potential and can be exploited in the development novel cardiac therapeutic agents.