Therapeutic effects and mechanisms of alcohol extracts from Polygala fallax Hemsl on endometriosis in rats

Endometriosis is a chronic estrogen-dependent inflammatory disease that significantly affects women's health. Polygala fallax Hemsl. (PFH), a traditional Zhuang medicine, has been frequently used for gynecological disorders. This study investigated the therapeutic effects and mechanisms of the alcohol extract of Polygala fallax Hemsl. (ae-PFH) in a rat model of endometriosis, as well as its potential for combination therapy. SD rats were divided into seven groups: control, model, PFH, mifepristone, PFH combined with mifepristone, exosomes, and PFH combined with exosomes. After 21 days of treatment, body weight, organ coefficients, and histopathological changes in uterine and ovarian tissues were analyzed. UPLC-Q-Exactive Orbitrap-MS identified active components in ae-PFH and serum samples, followed by molecular docking with key disease target proteins. Serum levels of inflammatory cytokines and hormones were measured using ELISA, while protein and mRNA expression of key regulatory factors were assessed via Western blot and q-PCR. Ae-PFH reduced lesion size and suppressed inflammation, angiogenesis, and pain by inhibitied the PI3K/AKT pathway. Additionally, in combination therapy, ae-PFH significantly enhanced therapeutic effects of mifepristone or exosomes derived from umbilical cord mesenchymal stem cells. These findings indicated that ae-PFH presentd a promising medical method for the treatment of endometriosis, exhibiting innovative potentiality for combination therapy.