Biochanin A as a potential agent in the disease therapy via mitochondria-mediated mechanisms.

Biochanin A (BCA), a naturally occurring phytoestrogen, derived from plants such as Trifolium pratense L. (red clover), has attracted considerable interest due to its diverse pharmacological properties. As a dietary supplement, BCA is commonly utilized to alleviate symptoms associated with estrogen deficiency. Beyond its estrogenic effects, accumulating evidence highlights its broad-spectrum bioactivities, including anti-cancer, anti-diabetes, neuroprotection, anti-inflammation, antioxidant, organ protection, etc. Mitochondrial dysfunction is increasingly recognized as a central pathological mechanism underlying numerous diseases, making it a pivotal therapeutic target. Despite extensive research on BCA's pharmacological effects, a comprehensive review of its mitochondria-mediated mechanisms remains lacking. Here, on the basis of sufficient and comprehensive literature screening, we systematically review the extraordinary therapeutic potential of BCA in both in vitro and in vivo through its modulation of mitochondria-mediated pathways, including mitochondria-dependent apoptosis, reactive oxygen species (ROS) homeostasis, mitochondrial dynamics (fusion/fission), bioenergetics and mitochondrial biogenesis, as well as mitophagy. With this specific mechanism perspective, it helps us better understand the important role of mitochondria in the development of diseases and better target mitochondria to develop therapeutic regimens. Emerging studies highlight BCA's significant efficacy in mitigating disease progression, positioning it as a promising candidate for clinical translation and future drug development.