Computational and experimental pharmacology to decode the efficacy of Theobroma cacao L. against doxorubicin-induced organ toxicity in EAC-mediated solid tumor-induced mice

Frontiers in Pharmacology

Pharmacology

Pranjal Kumar¹  Sudhanshu Shukla¹  Pukar Khanal²  Vishwambhar Vishnu Bhandare³  Harish R. Darasaguppe³  Rajesh K. Joshi³  Subarna Roy³  Arati Bhatkande³  Vishal S. Patil⁴  Priyanka P. Patil⁴  Basanagouda M. Patil⁵ 

[1] Department of Biosciences and Bioengineering, Indian Institute of Technology Dharwad, Dharwad, Karnataka, India;Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka, India;Indian Council of Medical Research- National Institute of Traditional Medicine, Belagavi, Karnataka, India;Indian Council of Medical Research- National Institute of Traditional Medicine, Belagavi, Karnataka, India;Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi, KLE Academy of Higher Education and Research (KAHER), Belagavi, Karnataka, India;PRES’s Pravara Rural College of Pharmacy Pravaranagar, Loni, Maharashtra, India;

关键词: cocoa;    cytotoxicity;    doxorubicin;    organ toxicity;    oxidative stress;   

DOI  :  10.3389/fphar.2023.1174867

 received in 2023-02-27, accepted in 2023-05-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background and objective: Doxorubicin is extensively utilized chemotherapeutic drug, and it causes damage to the heart, liver, and kidneys through oxidative stress. Theobroma cacao L (cocoa) is reported to possess protective effects against several chemical-induced organ damages and also acts as an anticancer agent. The study aimed to determine whether the administration of cocoa bean extract reduces doxorubicin-induced organ damage in mice with Ehrlich ascites carcinoma (EAC) without compromising doxorubicin efficacy.Methodology: Multiple in vitro methods such as cell proliferation, colony formation, chemo-sensitivity, and scratch assay were carried out on cancer as well as normal cell lines to document the effect of cocoa extract (COE) on cellular physiology, followed by in vivo mouse survival analysis, and the organ-protective effect of COE on DOX-treated animals with EAC-induced solid tumors was then investigated. In silico studies were conducted on cocoa compounds with lipoxygenase and xanthine oxidase to provide possible molecular explanations for the experimental observations.Results: In vitro studies revealed potent selective cytotoxicity of COE on cancer cells compared to normal. Interestingly, COE enhanced DOX potency when used in combination. The in vivo results revealed reduction in EAC and DOX-induced toxicities in mice treated with COE, which also improved the mouse survival time; percentage of lifespan; antioxidant defense system; renal, hepatic, and cardiac function biomarkers; and also oxidative stress markers. COE reduced DOX-induced histopathological alterations. Through molecular docking and MD simulations, we observed chlorogenic acid and 8′8 methylenebiscatechin, present in cocoa, to have the highest binding affinity with lipoxygenase and xanthine oxidase, which lends support to their potential in ameliorating oxidative stress.Conclusion: The COE reduced DOX-induced organ damage in the EAC-induced tumor model and exhibited powerful anticancer and antioxidant effects. Therefore, COE might be useful as an adjuvant nutritional supplement in cancer therapy.

【 授权许可】

Unknown   
Copyright © 2023 Patil, Kumar, Khanal, Patil, Darasaguppe, Bhandare, Bhatkande, Shukla, Joshi, Patil and Roy.