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

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

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. A 3, 5-diethoxycarbonyl-1, 4-dihydro-collidine (DDC)-induced c...

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Published in:Frontiers in pharmacology Vol. 15; p. 1341020
Main Authors: Meng, Qian, Zhu, Hongwen, Li, Yuanyuan, Peng, Xiaotian, Wang, Tianming, Huang, Hui, Zhou, Hu, Liu, Yuejia, Ru, Sujie, Wu, Jiasheng, Ma, Yueming
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 26-02-2024
Subjects:
cholestasis
liver fibrosis
PDGFRβ/PI3K/AKT
Pharmacology
proteomics
Yinchenzhufu decoction
Yinchenzhufu decoction
liver fibrosis
proteomics
PDGFRβ/PI3K/AKT
cholestasis
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Summary: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. 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. 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 (PDGFRβ), 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 PDGFRβ/PI3K/AKT pathway were further confirmed in mice and transforming growth factor-β-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 PDGFRβ expression. YCZFD substantially protects against DDC-induced CLF mainly through regulating the PDGFRβ/PI3K/AKT signaling pathway.
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Edited by: Yi Wu, Nanjing Agricultural University, China
Kapil Upadhyay, University of Michigan, United States
Hongxu Du, Southwest University, China
Reviewed by: Haifeng Wang, Shenyang Pharmaceutical University, China
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2024.1341020