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Phillygenin Inhibits TGF-β1-induced Hepatic Stellate Cell Activation and Inflammation: Regulation of the Bax/Bcl-2 and Wnt/β-catenin Pathways.
- Source :
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Inflammation [Inflammation] 2024 Aug; Vol. 47 (4), pp. 1403-1422. Date of Electronic Publication: 2024 Feb 23. - Publication Year :
- 2024
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Abstract
- Hepatic fibrosis (HF), a precursor to cirrhosis and hepatocellular carcinoma, is caused by abnormal proliferation of connective tissue and excessive accumulation of extracellular matrix in the liver. Notably, activation of hepatic stellate cells (HSCs) is a key link in the development of HF. Phillygenin (PHI, C <subscript>21</subscript> H <subscript>24</subscript> O <subscript>6</subscript> ) is a lignan component extracted from the traditional Chinese medicine Forsythiae Fructus, which has various pharmacological activities such as anti-inflammatory, antioxidant and anti-tumour effects. However, whether PHI can directly inhibit HSC activation and ameliorate the mechanism of action of HF has not been fully elucidated. Therefore, the aim of the present study was to investigate the in vitro anti-HF effects of PHI and the underlying molecular mechanisms. Transforming growth factor-β1 (TGF-β1)-activated mouse HSCs (mHSCs) and human HSCs (LX-2 cells) were used as an in vitro model of HF and treated with different concentrations of PHI for 24 h. Subsequently, cell morphological changes were observed under the microscope, cell viability was analyzed by MTT assay, cell cycle and apoptosis were detected by flow cytometry, and the mechanism of anti-fibrotic effect of PHI was explored by immunofluorescence, ELISA, RT-qPCR and western blot. The results showed that PHI suppressed the proliferation of TGF-β1-activated mHSCs and LX-2 cells, arrested the cell cycle at the G0/G1 phase, decreased the levels of α-SMA, Collagen I, TIMP1 and MMP2 genes and proteins, and promoted apoptosis in activated mHSCs and LX-2 cells. Besides, PHI reduced the expression of inflammatory factors in activated mHSCs and LX-2 cells, suggesting a potential anti-inflammatory effect. Mechanically, PHI inhibited TGF-β1-induced HSC activation and inflammation, at least in part through modulation of the Bax/Bcl-2 and Wnt/β-catenin pathways. Overall, PHI has significant anti-HF effects and may be a promising agent for the treatment of HF.<br /> (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Humans
Mice
Inflammation drug therapy
Inflammation metabolism
Liver Cirrhosis drug therapy
Liver Cirrhosis metabolism
Liver Cirrhosis pathology
beta Catenin metabolism
Cell Line
Anti-Inflammatory Agents pharmacology
Hepatic Stellate Cells drug effects
Hepatic Stellate Cells metabolism
Transforming Growth Factor beta1 metabolism
Wnt Signaling Pathway drug effects
Lignans pharmacology
Proto-Oncogene Proteins c-bcl-2 metabolism
bcl-2-Associated X Protein metabolism
Apoptosis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2576
- Volume :
- 47
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 38393550
- Full Text :
- https://doi.org/10.1007/s10753-024-01984-w