Natural Products Targeting Oxidative Stress-Inflammation Crosstalk in Endometriosis

Endometriosis is a chronic, estrogen-dependent inflammatory disorder marked by ectopic endometrial-like tissue growth, resulting in pelvic pain, infertility, and significant declines in quality of life. Despite extensive research, current therapies remain largely symptomatic and are often associated with recurrence, hormonal adverse effects, and compromised fertility outcomes. Growing evidence indicates that oxidative stress, chronic inflammation, mitochondrial dysfunction, altered immune surveillance and metabolic dysregulation are central drivers of lesion establishment and progression. However, these interconnected mechanisms are often examined in isolation, limiting translational progress.

We provide a comprehensive, integrative analysis of the molecular and cellular pathways underlying endometriosis, with particular emphasis on oxidative stress-inflammation crosstalk, signalling cascades supporting lesion survival, and emerging metabolic and mitochondrial targets. By critically synthesising recent experimental, preclinical, and clinical findings, this review highlights mechanistic overlaps that may explain therapeutic resistance and disease recurrence. Furthermore, it evaluates novel pharmacological and nutraceutical interventions targeting redox imbalance, inflammatory mediators, and intracellular signalling pathways, thereby expanding the conceptual framework beyond conventional hormonal suppression. Rising global endometriosis prevalence and its socioeconomic burden necessitate a shift from purely symptomatic management to mechanism-driven therapeutic strategies.

This review addresses that gap by consolidating dispersed evidence into a unified mechanistic perspective, identifying promising translational targets, and proposing future research directions. The insights provided will help in creating safer, fertility-preserving and more durable treatments. Thus, we categorise natural products by: (1) translational development stage (in vitro to clinical candidate); (2) regulatory pathway (dietary supplement, herbal medicine, or pharmaceutical); and (3) clinical context (e.g., pain control, recurrence prevention, or fertility preservation).

This structured, clinically-oriented framework distinguishes the present synthesis from mechanistic reviews and serves to guide both future research design and rational integration of natural products into endometriosis therapeutic strategies.