Advancing the frontiers of phytotherapy: a comprehensive review of botanical interventions targeting mitochondrial quality control to ameliorate endometriosis

Endometriosis (EMs) is a gynecological disorder affecting women of reproductive age. It is characterized by the ectopic implantation and infiltration of endometrial-like tissue and is associated with significant effects on fertility, pelvic function, and overall wellbeing. Clinically, it presents with progressive secondary dysmenorrhea, chronic pelvic pain, and infertility, leading to a substantial reduction in quality of life. Despite decades of research, the pathogenesis of EMs remains complex and is driven by interacting hormonal, immunological, inflammatory, and metabolic factors. Current treatment approaches, including hormonal suppression and surgical excision, provide only temporary relief and are associated with systemic side effects, functional limitations, and high recurrence rates. These limitations highlight the need for safer and more effective therapeutic strategies. Mitochondria play a central role in the development of EMs. Mitochondrial function is regulated by the mitochondrial quality control (MQC) system, which consists of several interconnected processes, including redox homeostasis, mitochondrial fission and fusion, mitophagy, biogenesis, and calcium signaling. Increasing evidence suggests that disruption of MQC is not merely a secondary effect but a key contributor to EMs pathogenesis. MQC dysfunction enables ectopic endometrial cells to evade apoptosis, promotes invasive proliferation, supports oxidative stress adaptation, and facilitates survival in unfavorable microenvironments. Plant-derived compounds have gained attention as potential modulators of MQC. These compounds exhibit multi-target effects, favorable safety profiles, and a wide range of bioactive structures. Experimental studies indicate that botanical agents, including flavonoids and terpenoids, can regulate multiple components of the MQC system. They reduce mitochondrial reactive oxygen species, modulate DRP1/OPA1-mediated mitochondrial dynamics, enhance PINK1-Parkin-dependent mitophagy, promote PGC-1α-mediated mitochondrial biogenesis, and maintain calcium homeostasis. Through these mechanisms, phytochemicals improve mitochondrial function, inhibit abnormal cell survival signaling, induce apoptosis in ectopic lesions, and contribute to the restoration of endometrial homeostasis.