Effect of Artocarpus lakoocha R. Extract against Doxorubicin Induced Cardiotoxicity in Wistar Rats – In silico and In vivo studies

Background: Doxorubicin is anticancer antibiotic used in treatment of variety of malignancy. Its use has been limited due to dose related Cardiotoxicity. Objectives: To evaluate role of Artocarpus lakoocha Roxb. on Doxorubicin produced Cardiotoxicity in Wistar rats and to Predict the effect of Artocarpus lakoocha Roxb. by In-silico method. Methodology: Insilico studies such as Network pharmacology and molecular docking studies were performed to determine the effect of Artocarpus lakoocha Roxb. on CVS. Invitro studies conducted to determine Cardioprotective activity of the ethanolic plant extract. Cardiotoxicity induced with DOX (2.5 mg/kg i.p) in six injections given alternatively for fourteen days to make a total cumulative dose of 15 mg/kg body weight. Comparative studies were done between Treatment group, Dox 2.5 mg/kg on alternate day for 2 weeks followed by ethanolic extract (100 and 200 mg/kg p.o) for 2 weeks and Pretreated group, ethanolic extract (100 and 200 mg/kg p.o) pretreated for 2 weeks followed by Dox 2.5 mg/kg on alternative day for 2 weeks. Animals were observed for change in food, water intake, body weight, ECG changes, Cardiac markers such as CK-MB, LDH and cTn I, Antioxidant enzymes such as GSH, Catalases, SOD and MDA were monitored. Heart histopathological studies carried out to evaluate cardiotoxicity. Conclusion: The bioactives of Artocarpus lakoocha R. such as rutin, Quercetin, Artocarpesin and targets NOS, AKT1, KDR, EGFR and ADORA1 are analysed to be effective in protecting the Heart from CVS disorders. Animals treated with high dose of ethanolic extract ameliorated DOX induced electrocardiogram changes and also alleviated Dox induced increase in serum CK-MB, LDH and cTn I levels. Treatment studies provided more significant results when compared with preventive studies.