Endometriosis (EMS) is an
estrogen-dependent gynecological disease with a low autophagy level of ectopic endometrial stromal cells (eESCs). Impaired NK cell cytotoxic activity is involved in the clearance obstruction of the ectopic endometrial tissue in the abdominopelvic cavity.
Protopanaxadiol (
PPD) and
protopanaxatriol (PPT) are two metabolites of
ginsenosides, which have profound biological functions, such as anti-
cancer activities. However, the role and mechanism of
ginsenosides and metabolites in
endometriosis are completely unknown. Here, we found that the compounds
PPD, PPT, ginsenoside-Rg3 (G-Rg3),
ginsenoside-Rh2 (G-Rh2), and
esculentoside A (EsA) led to significant decreases in the viability of eESCs, particularly
PPD (IC50 = 30.64 µM). In vitro and in vivo experiments showed that
PPD promoted the expression of
progesterone receptor (PR) and downregulated the expression of
estrogen receptor α (ERα) in eESCs. Treatment with
PPD obviously induced the autophagy of eESCs and reversed the inhibitory effect of
estrogen on eESC autophagy. In addition, eESCs pretreated with
PPD enhanced the cytotoxic activity of NK cells in response to eESCs.
PPD decreased the numbers and suppressed the growth of ectopic lesions in a mouse EMS model. These results suggest that
PPD plays a role in anti-EMS activation, possibly by restricting
estrogen-mediated autophagy regulation and enhancing the cytotoxicity of NK cells. This result provides a scientific basis for potential therapeutic strategies to treat EMS by
PPD or further structural modification.