Therapeutic strategies in traditional Chinese medicine for premature ovarian failure: Modulation of oxidative stress and autophagy-apoptosis via the AMPK/mTOR pathway.

Abstract

Premature ovarian failure (POF), also referred to as premature ovarian insufficiency (POI), is a multifactorial reproductive endocrine disorder characterized by amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels before the age of 40. Emerging evidence links its pathogenesis to oxidative stress and dysregulation of the autophagy-apoptosis balance in ovarian cells. Excessive accumulation of reactive oxygen species (ROS) impairs mitochondrial function in oocytes, while aberrant autophagy and granulosa cell apoptosis accelerate the depletion of primordial follicles. The AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway serves as a critical nexus between energy metabolism, oxidative stress, and cell survival. Traditional Chinese medicine (TCM), with its multi-component and multi-target characteristics, has demonstrated unique advantages in modulating the AMPK/mTOR pathway to restore ovarian function. This review synthesizes recent findings on single herbs, classical formulas, and non-pharmacological therapies (acupuncture and moxibustion). Mechanistic studies have revealed that these interventions can activate AMPK, inhibit mTOR overactivation, enhance Nrf2-mediated antioxidant defenses, reduce ROS production, and rebalance autophagy and apoptosis via pathways such as PI3K/Akt and SIRT1/p53. By aligning stage-specific regulation of AMPK/mTOR signaling with the TCM principle of syndrome differentiation, this integrative approach provides theoretical guidance for precise, personalized treatment to optimize multi-target strategies for POF management.