Article ; Online: Jiawei Taohe Chengqi Decoction attenuates hepatic fibrosis by preventing activation of HSCs through regulating Src/ERK/Smad3 signal pathway.
2022 Volume 305, Page(s) 116059
Abstract: Ethnopharmacological relevance: Jiawei Taohe Chengqi Decoction (JTCD) is a Traditional Chinese Medicine (TCM) formula modified from Taohe Chengqi Decoction in the classic ancient literature of TCM "Treatise on Febrile Diseases". Clinical and ... ...
| Abstract | Ethnopharmacological relevance: Jiawei Taohe Chengqi Decoction (JTCD) is a Traditional Chinese Medicine (TCM) formula modified from Taohe Chengqi Decoction in the classic ancient literature of TCM "Treatise on Febrile Diseases". Clinical and pharmacological studies have shown that JTCD has a therapeutic effect on hepatic encephalopathy, non-alcoholic fatty liver, cirrhotic ascites, and can alleviate acute liver injury in rats. Our previous studies confirmed that JTCD could alleviate hepatic fibrosis and activation of hepatic stellate cells (HSCs). However, its mechanism remains unclear. Aim of the study: This study aimed to elucidate the mechanism of Src Signal on hepatic fibrosis and HSCs activation, and whether JTCD inhibited hepatic fibrosis and HSCs activation through affecting Src Signal. Materials and methods: In vivo, sixty specific pathogen free male C57/BL6 mice were divided into following six groups: Control group, Model group, SARA group, JTCD low dose group, JTCD medium dose group and JTCD high dose group. Then we established a carbon tetrachloride (CCL Results: We identified 135 chemical components in the water extract of JTCD, and the water extract of JTCD contains a variety of anti-hepatic fibrosis components. Compared to the model group, hepatic fibrosis performance was significantly improved, the serum levels of ALT and AST were significantly decreased in JTCD groups and SARA group, IHC staining and western blot results indicated that JTCD decreased the expressions of α-smooth muscle actin (α-SMA), phospho-Src (Tyr416), phospho-ERK1/2 and phospho-Smad3. In vitro, JTCD-containing serum could significantly decrease the protein expressions of α-SMA, phospho-Src (Tyr416), phospho-ERK1/2 and phospho-Smad3 according to the results of western-blot and immunofluorescence, in addition, JTCD-containing serum inhibited the mobility and activation of LX-2. What's more, after intervening with Src-shRNA, ERK1/2 agonists/inhibitors and JTCD-containing serum, the western-blot results showed that Src/ERK/Smad3 signal has an important role in hepatic fibrosis and HSCs, and JTCD attenuates hepatic fibrosis by preventing activation of HSCs through regulating Src/ERK/Smad3 signal pathway. Conclusions: The results showed that Src kinase promoted hepatic fibrosis and HSCs activation through the ERK/Smad3 signal pathway. More importantly, the mechanism by which JTCD attenuated hepatic fibrosis and HSCs activation was by inhibiting the Src/ERK/Smad3 signal pathway. |
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| MeSH term(s) | Animals ; Humans ; Male ; Mice ; Carbon Tetrachloride/pharmacology ; Hepatic Stellate Cells ; Liver ; Liver Cirrhosis/chemically induced ; Liver Cirrhosis/drug therapy ; Liver Cirrhosis/metabolism ; MAP Kinase Signaling System ; RNA, Small Interfering ; Signal Transduction ; Smad3 Protein/metabolism ; Transforming Growth Factor beta1/metabolism |
| Chemical Substances | Carbon Tetrachloride (CL2T97X0V0) ; RNA, Small Interfering ; Smad3 Protein ; SMAD3 protein, human ; Transforming Growth Factor beta1 |
| Language | English |
| Publishing date | 2022-12-19 |
| Publishing country | Ireland |
| Document type | Journal Article |
| ZDB-ID | 134511-4 |
| ISSN | 1872-7573 ; 0378-8741 |
| ISSN (online) | 1872-7573 |
| ISSN | 0378-8741 |
| DOI | 10.1016/j.jep.2022.116059 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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