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Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway.

Abstract：

:Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of liver fibrosis. In this manner, we carried out in vitro studies for the purpose of investigating the anti-fibrosis impact of PD. Activation of hepatic stellate cells was evaluated by means of the detection of the proliferation of HSCs and the expression of specific proteins. We discovered the fact that PD had the potential of activating HSCs. Thereafter, we detected the apoptosis and autophagy of the HSCs; as the results suggested, PD induced apoptosis and autophagy of the HSCs. It augmented the expression level of apoptotic proteins that included Bax, Cytochrome C (cyto-c), cleaved caspase3 and cleaved caspase9, in addition to the autophagy relevant proteins, for instance, LC3II, beclin1, Atg5 and Atg9. Further research was carried out for the investigation of the underlying molecular mechanism, and discovered that PD promoted the phosphorylation of JNK and c-Jun. Treating the JNK inhibitor P600125 inhibited the effect of PD, confirming the impact of PD on the regulation of JNK/c-Jun pathway. Thus, we speculated that PD alleviates liver fibrosis and activation of hepatic stellate via promoting phosphorylation of JNK and c-Jun and further altering the autophagy along with apoptosis of HSCs.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Liu YM,Cong S,Cheng Z,Hu YX,Lei Y,Zhu LL,Zhao XK,Mu M,Zhang BF,Fan LD,Yu L,Cheng ML

doi

10.1016/j.ejphar.2020.172946

subject

Has Abstract

pub_date

2020-06-05 00:00:00

pages

172946

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(20)30038-8

journal_volume

876

pub_type

杂志文章

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Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway.