Publication: Effect of 3-HBI on Liver Fibrosis via the TGF-β/SMAD2/3 Pathway on the Human Hepatic Stellate Cell Model
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Issued Date
2025-07-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-105010323763
Journal Title
International Journal of Molecular Sciences
Volume
26
Issue
13
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.26 No.13 (2025)
Suggested Citation
Khongpiroon C., Buakaew W., Brindley P.J., Potikanond S., Daowtak K., Thongsri Y., Potup P., Usuwanthim K. Effect of 3-HBI on Liver Fibrosis via the TGF-β/SMAD2/3 Pathway on the Human Hepatic Stellate Cell Model. International Journal of Molecular Sciences Vol.26 No.13 (2025). doi:10.3390/ijms26136022 Retrieved from: https://hdl.handle.net/20.500.14740/21188
Corresponding Author(s)
Other Contributor(s)
Abstract
Liver fibrosis can progress to irreversible cirrhosis if the underlying causes remain, and this can in turn develop into hepatocellular carcinoma (HCC). Despite these adverse outcomes, liver fibrosis can be reversed. Consequently, research has focused on substances that target liver fibrosis to prevent or reduce its progression. This study deals with the potential anti-fibrotic action of 3-hydroxy-β-ionone (3-HBI), a bioactive compound found in many plants. To assess the putative effects of 3-HBI, pro-inflammatory cytokine production and the expression of genes and proteins associated with the TGF-β/SMAD2/3 pathway were monitored following exposure to 3-HBI. Initially, cells of the human hepatic stellate cell line LX-2 were treated with TGF-β1 to simulate fibrogenesis. Following the exposure of activated LX-2 cells to 3-HBI, the production of pro-fibrotic substances was significantly reduced. Molecular docking studies revealed that 3-HBI exhibited a high binding affinity for key proteins in the TGF-β/SMAD2/3 pathway. Analyses using qRT-PCR and Western blotting revealed that 3-HBI suppressed the expression of TIMP1, MMP2, MMP9, COL1A1, COL4A1, SMAD2, SMAD3, SMAD4, MMP2, and ACTA2. Together, these findings demonstrate that 3-HBI inhibited the activation of LX-2 cells and significantly reduced the proinflammatory responses triggered by TGF-β1. Accordingly, we confirmed the noteworthy potential of 3-HBI as a therapeutic agent to prevent and treat liver fibrosis, effected by its modulation of the TGF-β/SMAD2/3 signaling pathway.