The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity.
The ginsenoside PPD exerts anti-endometriosis effects by suppressing estrogen receptor-mediated inhibition of endometrial stromal cell autophagy and NK cell cytotoxicity.
复制标题
人参皂苷 PPD 通过抑制雌激素受体介导的子宫内膜基质细胞自噬和 NK 细胞的细胞毒性发挥抗子宫内膜异位症作用
DOI：
10.1038/s41419-018-0581-2
复制
发表时间：
2018-05-01
影响因子：
9
通讯作者：
Li MQ
中科院分区：
文献类型：
--
作者：
Zhang B;Zhou WJ;Gu CJ;Wu K;Yang HL;Mei J;Yu JJ;Hou XF;Sun JS;Xu FY;Li DJ;Jin LP;Li MQ
子宫内膜异位症(EMS)是一种雌激素依赖型妇科疾病，异位子宫内膜间质细胞(EESCs)自噬水平低。NK细胞细胞毒活性受损与腹盆腔异位内膜组织清除障碍有关。原人参二醇(PPD)和原人参三醇(PPT)是人参皂苷的两种代谢产物，具有广泛的抗癌等生物学功能。然而，人参皂苷及其代谢物在子宫内膜异位症中的作用和机制尚不清楚。在这里，我们发现化合物PPD、PPT、人参皂苷-Rg3(G-Rg3)、人参皂苷-Rh2(G-Rh2)和七叶皂苷A(Esa)导致EESCs的存活率显著下降，尤其是Ppd(IC50 = 30.64 µM)。体内外实验表明，PPD可促进EESCs孕激素受体(PR)的表达，下调雌激素受体α(ERα)的表达。PPD可明显诱导EESCs自噬，并逆转雌激素对EESC自噬的抑制作用。此外，经PPD预处理的eESCs可增强NK细胞对eESCs的杀伤活性。PPD可减少小鼠EMS模型中异位病变的数量并抑制其生长。这些结果表明，PPD可能通过抑制雌激素介导的自噬调节和增强NK细胞的细胞毒作用而发挥抗EMS的作用。这一结果为通过PPD或进一步的结构修饰治疗EMS的潜在治疗策略提供了科学依据。
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.
登录
查看更多内容
影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
5.4
作者：
Huang G;Zou B;Lv J;Li T;Huai G;Xiang S;Lu S;Luo H;Zhang Y;Jin Y;Wang Y
通讯作者：
Wang Y
影响因子：
2.7
作者：
Bulun SE;Cheng YH;Pavone ME;Xue Q;Attar E;Trukhacheva E;Tokunaga H;Utsunomiya H;Yin P;Luo X;Lin Z;Imir G;Thung S;Su EJ;Kim JJ
通讯作者：
Kim JJ
DOI：
10.1016/s0889-8545(05)70302-8
发表时间：
1997-06-01
影响因子：
3.2
作者：
Eskenazi, B;Warner, ML
通讯作者：
Warner, ML
影响因子：
3.5
作者：
Leung, Kar Wah;Cheng, Yuen-Kit;Wong, Ricky N. S.
通讯作者：
Wong, Ricky N. S.