Ameliorative Effects of Quercetin and Metformin and Their Combination Against Experimental Endometriosis in Rats.

Endometriosis, as the leading cause of infertility, is attributed to oxidative stress, inflammation, and autophagy dysregulation. This study was conducted to evaluate the effect of quercetin and metformin, alone or in combination, on the ectopic and eutopic endometrial tissues in a rat model of endometriosis. We divided 60 female rats into 6 groups, including SH, Endo, Endo + Oil, Endo + Q, Endo + M, and Endo + Q + M. The last five groups underwent a surgery, so that we could induce endometriosis, and after 4 weeks, daily treatment began, lasting for a month. Subsequently, the size and histoarchitecture of the endometrial implants, serum levels of 17β-estradiol, progesterone and tumor necrosis factor (TNF)-α, and markers of oxidative stress and autophagy were assessed utilizing ELISA and gene expression analysis. Our results shed light to the fact that serum TNF-α and 17β-estradiol levels significantly increased in endometriosis rats. Moreover, NADPH: quinone oxidoreductase (NQO1) enzyme activity and gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and autophagy markers significantly decreased; meanwhile, mammalian target of rapamycin (mTOR) gene expression increased in the ectopic endometrial tissues, as compared with eutopic ones. Surprisingly, our results demonstrated that the treatment in which we applied the combination of quercetin and metformin significantly reversed these changes and had a pronounced effect on the endometrial implant size and gene expression levels of mTOR and autophagy markers in ectopic endometrium. The findings of the present study suggest that quercetin, metformin, and their combination were of potential therapeutic effects on the rat model of endometriosis.