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Abstract Title:

Ginsenoside PPD inhibit the activation of HSCs by directly targeting TGFβR1.

Abstract Source:

Int J Biol Macromol. 2022 Jan 1 ;194:556-562. Epub 2021 Nov 22. PMID: 34822828

Abstract Author(s):

Shouli Yuan, Meng Dong, Hanlin Zhang, Xiaoxiao Jiang, Chunlong Yan, Rongcai Ye, Huiqiao Zhou, Li Chen, Huiru Lian, Wanzhu Jin

Article Affiliation:

Shouli Yuan

Abstract:

TGFβ1 signaling pathway is associated with many diseases, which can induce the activation of hepatic stellate cells (HSCs) and induce liver fibrosis. Studies have shown that 20S-protopanaxadiol (PPD) has a therapeutic effect on liver fibrosis, but the target is unknown. In this study, we confirmed that PPD reduced the mRNA expression of downstream genes of the TGFβ1 pathway, which suggesting PPD is associated with the TGFβ1 pathway. The protein dissociation temperature and dissociation constant (Kd) of PPD on TGFβR1 and TGFβR2 were determined, which showed that PPD combined with TGFβR1 (Kd = 1.54 μM). The docking and simulation methods were used to find their binding sites. Site mutations, protein expression and in vitro binding experiments were performed to demonstrated these sites. In particular, these sites of TGFβR1 were also the active sites of TGFβR2. Therefore, we speculated that PPD blocked the combination of TGFβR1 and TGFβR2 by binding to the D57, R58, P59, and N78 of the TGFβR1 extracellular domain. Thus, PPD could block the transmission of TGFβ1 pathway and inhibit the activation of HSCs, and treating fibrosis. Our studies showed that PPD has the potential to treat diseases related to the TGFβ1 pathway and broadens its clinical application.

Study Type : In Vitro Study

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Sayer Ji
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