Cardioprotective Potential of Machilus macrantha Against Adriamycin-Induced Cardiotoxicity: An In Vivo Study

Background: Machilus macrantha Nees (Lauraceae), commonly known as Gulmau, is a large tree found in Bihar and the Deccan Peninsula (Western Ghats of Maharashtra), India. In-silico biological activity predictions of its alkaloid machiline have revealed fibrinolytic activity, oxygen and free radical scavenging ability, and cardiotonic potential. Phenolic compounds isolated from M. macrantha have also demonstrated free radical scavenging, cytoprotective, and calcium channel antagonistic activities.

Purpose: Reactive oxygen species (ROS) overproduction and calcium overload are key factors involved in ischemia and oxidative stress-induced cardiac injury. The present study aimed to evaluate the antioxidant potential and cardioprotective effect of the methanolic extract of Machilus macrantha roots against doxorubicin-induced cardiotoxicity in rats.

Methods: In vitro antioxidant activity of the methanolic extract was evaluated using the DPPH radical scavenging assay. Cardioprotective activity was assessed in Albino Wistar male rats using a doxorubicin-induced cardiotoxicity model. Animals were pre-treated orally with methanolic extract of M. macrantha (100 and 200 mg/kg). Electrocardiographic (ECG) changes, hemodynamic parameters, cardiac injury markers, and antioxidant enzyme levels were evaluated.

Results: The methanolic extract showed significant antioxidant activity in the DPPH assay. Doxorubicin administration produced marked ECG alterations (depressed ST segment, decreased R–R and QRS intervals, and increased QT interval) and increased serum levels of cardiac injury markers such as CK-MB, LDH, and lipid peroxidation (LPO). It also significantly reduced endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH). Pre-treatment with M. macrantha extract significantly improved ECG parameters, reduced CK-MB, LDH, and LPO levels, and restored CAT, SOD, and GSH levels compared with disease control animals.

Conclusion: The methanolic extract of Machilus macrantha roots exhibits significant cardioprotective and antioxidant effects against doxorubicin-induced cardiotoxicity, likely through restoration of endogenous antioxidant defense systems and improvement of electrocardiographic abnormalities.

Pranjal P. Gujarathi is a currently serves as an Assistant Professor in the Department of Pharmacology at SVKM NMIMS Global University, School of Pharmacy and Technology Management, Dhule, Maharashtra, India and Ph.D. Scholar at Bhagwan Mahavir University, Gujarat, India, and she has collaborated with Bhabha Atomic Research Centre, India, as a Senior Research Fellow, focusing on the toxicity assessment of radiopharmaceuticals. She has secured research grants exceeding ₹1 lakh from various Indian funding agencies. Her research contributions span neuroprotection, dermatology, cardiology, and complementary and alternative system of medicine, with numerous published research and review papers. Additionally, she has authored five books and contributed to over five book chapters with national and international publishers. Mrs. Gujarathi has been invited as a speaker at prestigious international and national conferences in Malaysia, the USA, China, the UK, etc, both within and beyond India. She also holds a position as editor and reviewer team member of various national journals. Her outstanding research and presentation skills have earned her multiple national and international awards, including recognition as the Best Presenter. She has also been honoured with the Best Woman Researcher Award by the Bureau of Indian Standards and more than 10 awards in national and international Conferences.