The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity

Cell Death & Disease
Bing ZhangMing-Qing Li

Abstract

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 E...Continue Reading

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Citations

Mar 4, 2019·Cellular and Molecular Life Sciences : CMLS·Wen-Jie ZhouMing-Qing Li
Oct 31, 2020·Human Reproduction Update·Gabriela F MeresmanMatthias W Laschke
Aug 8, 2021·Cells·Karolina NowakWioletta Ratajczak-Wrona
Oct 1, 2021·Recent Patents on Anti-cancer Drug Discovery·Sheng-Xiong ZhangLi-Zhu Lin

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Methods Mentioned

BETA
hysterectomy
flow cytometry
PCR
protein assay

Software Mentioned

Cellquest
GraphPad Prism

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