Phomopsterone B Alleviates Liver Fibrosis through mTOR-Mediated Autophagy and Apoptosis Pathway

Autor: Mei-Lin Peng, Li-Jie Zhang, Yan Luo, Shi-Ying Xu, Xing-Mei Long, Jun-Li Ao, Shang-Gao Liao, Qin-Feng Zhu, Xun He, Guo-Bo Xu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecules, Vol 29, Iss 2, p 417 (2024)
Druh dokumentu: article
ISSN: 29020417
1420-3049
DOI: 10.3390/molecules29020417
Popis: Liver fibrosis is the initial pathological process of many chronic liver diseases. Targeting hepatic stellate cell (HSC) activation is an available strategy for the therapy of liver fibrosis. We aimed to explore the anti-liver fibrosis activity and potential mechanism of phomopsterone B (PB) in human HSCs. The results showed that PB effectively attenuated the proliferation of TGF-β1-stimulated LX-2 cells in a concentration-dependent manner at doses of 1, 2, and 4 μM. Quantitative real-time PCR and Western blot assays displayed that PB significantly reduced the expression levels of α-SMA and collagen I/III. AO/EB and Hoechst33342 staining and flow cytometry assays exhibited that PB promoted the cells’ apoptosis. Meanwhile, PB diminished the number of autophagic vesicles and vacuolated structures, and the LC3B fluorescent spots indicated that PB could effectively inhibit the accretion of autophagosomes in LX-2 cells. Moreover, rapamycin and MHY1485 were utilized to further investigate the effect of mTOR in autophagy and apoptosis. The results demonstrated that PB regulated autophagy and apoptosis via the mTOR-dependent pathway in LX-2 cells. In summary, this is the first evidence that PB effectively alleviates liver fibrosis in TGF-β1-stimulated LX-2 cells, and PB may be a promising candidate for the prevention of liver fibrosis.
Databáze: Directory of Open Access Journals
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