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Quantitative proteomics reveals the protective effects of Yinchenzhufu decoction against cholestatic liver fibrosis in mice by inhibiting the PDGFRβ/PI3K/AKT pathway

文献类型：期刊论文

作者Meng, Qian3,4; Zhu, Hongwen3; Li, Yuanyuan4; Peng, Xiaotian4; Wang, Tianming4; Huang, Hui3; Zhou, Hu2,3; Liu, Yuejia1,3; Ru, Sujie1,3; Wu, Jiasheng4
刊名FRONTIERS IN PHARMACOLOGY
出版日期2024-02-26
卷号15页码:13
关键词Yinchenzhufu decoction proteomics cholestasis liver fibrosis PDGFR beta/PI3K/AKT
DOI10.3389/fphar.2024.1341020
通讯作者Wu, Jiasheng(wujiasheng@shutcm.edu.cn) ; Ma, Yueming(mayueming_117@hotmail.com)
英文摘要Introduction: Yinchenzhufu decoction (YCZFD) is a traditional Chinese medicine formula with hepatoprotective effects. In this study, the protective effects of YCZFD against cholestatic liver fibrosis (CLF) and its underlying mechanisms were evaluated. Methods: A 3, 5-diethoxycarbonyl-1, 4-dihydro-collidine (DDC)-induced cholestatic mouse model was used to investigate the amelioration of YCZFD on CLF. Data-independent acquisition-based mass spectrometry was performed to investigate proteomic changes in the livers of mice in three groups: control, model, and model treated with high-dose YCZFD. The effects of YCZFD on the expression of key proteins were confirmed in mice and cell models. Results: YCZFD significantly decreased the levels of serum biochemical, liver injury, and fibrosis indicators of cholestatic mice. The proteomics indicated that 460 differentially expressed proteins (DEPs) were identified among control, model, and model treated with high-dose YCZFD groups. Enrichment analyses of these DEPs revealed that YCZFD influenced multiple pathways, including PI3K-Akt, focal adhesion, ECM-receptor interaction, glutathione metabolism, and steroid biosynthesis pathways. The expression of platelet derived growth factor receptor beta (PDGFR beta), a receptor associated with the PI3K/AKT and focal adhesion pathways, was upregulated in the livers of cholestatic mice but downregulated by YCZFD. The effects of YCZFD on the expression of key proteins in the PDGFR beta/PI3K/AKT pathway were further confirmed in mice and transforming growth factor-beta-induced hepatic stellate cells. We uncovered seven plant metabolites (chlorogenic acid, scoparone, isoliquiritigenin, glycyrrhetinic acid, formononetin, atractylenolide I, and benzoylaconitine) of YCZFD that may regulate PDGFR beta expression. Conclusion: YCZFD substantially protects against DDC-induced CLF mainly through regulating the PDGFR beta/PI3K/AKT signaling pathway.
WOS关键词PDGF ; PROLIFERATION ; COLLAGEN
资助项目National Natural Science Foundation of China[81773871] ; SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001178973600001
出版者FRONTIERS MEDIA SA
源URL[http://119.78.100.183/handle/2S10ELR8/310196]  
专题新药研究国家重点实验室
通讯作者Wu, Jiasheng; Ma, Yueming
作者单位1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Jiangsu, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Analyt Res Ctr Organ & Biol Mol, State Key Lab Drug Res, Shanghai, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Sch Pharm, Dept Pharmacol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Meng, Qian,Zhu, Hongwen,Li, Yuanyuan,et al. Quantitative proteomics reveals the protective effects of Yinchenzhufu decoction against cholestatic liver fibrosis in mice by inhibiting the PDGFRβ/PI3K/AKT pathway[J]. FRONTIERS IN PHARMACOLOGY,2024,15:13.
APA Meng, Qian.,Zhu, Hongwen.,Li, Yuanyuan.,Peng, Xiaotian.,Wang, Tianming.,...&Ma, Yueming.(2024).Quantitative proteomics reveals the protective effects of Yinchenzhufu decoction against cholestatic liver fibrosis in mice by inhibiting the PDGFRβ/PI3K/AKT pathway.FRONTIERS IN PHARMACOLOGY,15,13.
MLA Meng, Qian,et al."Quantitative proteomics reveals the protective effects of Yinchenzhufu decoction against cholestatic liver fibrosis in mice by inhibiting the PDGFRβ/PI3K/AKT pathway".FRONTIERS IN PHARMACOLOGY 15(2024):13.

入库方式： OAI收割

来源：上海药物研究所

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