Abstract

DIABETIC CARDIOTOXICITY: EMERGING MECHANISMS, CLINICAL IMPLICATIONS, AND THERAPEUTIC INNOVATIONS WITH MEDICINAL PLANTS

Devika Hangirkar and Nayeem A. Khatib*

Abstract

Diabetic cardiotoxicity, a leading cause of morbidity and mortality in the global diabetic population, arises from a complex interplay of metabolic dysregulation, oxidative stress, inflammation, and epigenetic alterations. This review synthesizes emerging mechanisms, clinical implications, and therapeutic innovations, with a focus on the underexplored potential of medicinal plants. Chronic hyperglycemia drives mitochondrial dysfunction, lipotoxicity, and NLRP3 inflammasome activation, culminating in myocardial fibrosis, diastolic dysfunction, and heart failure. While SGLT2 inhibitors and GLP-1 agonists represent breakthroughs in reducing cardiovascular events, disparities in access persist, particularly in low- and middle-income countries (LMICs). Medicinal plants, such as Ginkgo biloba (SIRT1/PGC-1α activation), Curcuma longa (Nrf2/NF-κB modulation), and Berberis vulgaris (AMPK/NLRP3 inhibition), demonstrate cardioprotective effects in preclinical models by targeting oxidative stress, inflammation, and fibrosis. Clinical evidence, though preliminary, supports their role in improving endothelial function and glycemic control. However, challenges like poor bioavailability, inconsistent dosing, and limited large-scale trials hinder translation. Emerging therapies, including ferroptosis inhibitors and epigenetic editing, alongside lifestyle interventions and AI-driven glucose monitoring, offer complementary strategies. This review underscores the urgency of integrating traditional herbal knowledge with modern precision approaches to address the growing burden of diabetic cardiomyopathy. Future research must prioritize clinical validation of phytochemicals, bioengineering solutions for enhanced delivery, and equitable access to therapies in LMICs. By bridging mechanistic insights with holistic interventions, this work charts a path toward mitigating diabetic cardiotoxicity in an era of escalating diabetes prevalence.

Keywords: Diabetic Cardiomyopathy, Oxidative Stress, Medicinal Plants, NLRP3 Inflammasome, Ferroptosis.