Plant metabolites targeting mitochondrial dysfunction in cardiovascular diseases: pharmacological mechanisms and combination strategies

Abstract

Cardiovascular diseases (CVDs) are closely associated with mitochondrial dysfunction, including impaired mitochondrial biogenesis, abnormal mitochondrial dynamics, excessive oxidative stress, dysregulated mitophagy, and disorders of energy metabolism. Accumulating evidence indicates that natural products exert significant cardioprotective effects by coordinately regulating multiple mitochondrial pathways, thereby alleviating myocardial injury and slowing disease progression. This review systematically summarises recent advances in natural metabolites and their rational combination strategies for cardiovascular diseases, with a particular focus on mitochondrial regulation. Representative metabolites, including flavonoids, alkaloids, saponins, and polyphenols, regulate key signalling pathways such as SIRT1/PGC-1α, AMPK, Nrf2, PINK1/Parkin, and Drp1/MFN2 to restore mitochondrial homeostasis. Importantly, natural metabolite combinations further demonstrate synergistic and complementary effects through coordinated regulation of distinct mitochondrial pathways. For example, EGCG and Rhein cooperatively alleviate myocardial ischemia/reperfusion injury by simultaneously suppressing oxidative stress and TLR4-mediated inflammatory signalling. Collectively, this review highlights the considerable potential of natural products and their rational combinations as therapeutic strategies for cardiovascular diseases through the modulation of mitochondrial function.