Mitigating mitochondrial dysfunction: a novel strategy for Chinese botanical drugs against osteoporosis.

Osteoporosis (OP) is a chronic metabolic disease characterized by reduced bone mass and impaired bone microstructure, posing a significant global health threat. Mitochondria, as the body's energy regulators, participate in numerous critical biological processes, and their dysfunction is a precipitating factor in various diseases. Accumulating evidence indicates that mitochondrial dysfunction-including abnormalities in mitochondrial biogenesis, dynamics, oxidative stress, and mitophagy-play a pivotal role in OP pathogenesis. Chinese botanical drugs (CBDs), leveraging their advantages of "multiple targets, multi-levels, and holistic regulation," are widely applied to modulate mitochondrial function and alleviate mitochondrial dysfunction, emerging as a novel therapeutic direction for OP prevention and treatment. This review summarizes the core mechanisms by which mitochondrial dysfunction drives OP, and systematically catalogs CBD-derived natural chemical metabolites (e.g., resveratrol) and classic formulations (e.g., Zuogui Pill) that target and ameliorate mitochondrial dysfunction. This review aims to establish a "CBD-mitochondrial-bone" research paradigm, highlight the most promising CBD candidates for alleviating mitochondrial dysfunction, and provide a theoretical basis and novel insights for developing precision treatment strategies for OP based on ameliorating mitochondrial dysfunction.