Multi-Target Anti-Endometriosis Mechanisms of Camellia sinensis Polyphenols: An Integrated Computational and Transcriptomic Study

Endometriosis is a chronic inflammatory disorder linked to estrogen, affecting about 10% of women of childbearing age. Current treatments, including hormonal and surgical options, have limitations related to side effects and recurrence. Green tea (Camellia sinensis) is rich in polyphenols and has known anti-estrogenic, anti-angiogenic, and anti-inflammatory effects, but its mechanism against endometriosis is unclear. Using phytochemical profiling, network pharmacology, and molecular docking, we identified twenty significant metabolites. From 619 predicted compound targets and 3065 endometriosis-related genes, we identified 292 common targets that formed a connected PPI network (p < 1.0 × 10−16) centered on key proteins such as TP53 and ESR1, with components linked to estrogenic and inflammatory processes. Functional enrichment revealed key processes such as oxidative stress and cell proliferation. Transcriptomic analysis confirmed consistent downregulation of ESR1 in ectopic endometrial tissue. Molecular docking confirmed that ECG has a strong affinity for ESR1 (−7.84 kcal/mol), marmesin binds notably to PGR, and a unique EGCG–EP300/CREBBP epigenetic pathway exists. These findings outline a dual endocrine–inflammatory mechanism in which ESR1 emerges as the most strongly supported target—validated by network centrality, reproducible transcriptomic down-regulation, and docking—while CYP19A1 is nominated as a plausible complementary node, and suggest that C. sinensis polyphenols merit experimental evaluation as complementary anti-endometriotic agents.