Anti-fibrotic effects of brevilin A in hepatic fibrosis via inhibiting the STAT3 signaling pathway.

Abstract

Hepatic fibrosis is a chronic liver disease characterized by the accumulation of extracellular matrix (ECM). Activation of hepatic stellate cells (HSCs) after repetitive liver damage is a key event in hepatic fibrogenesis. As part of ongoing research projects to identify pharmacologically effective natural products, the phytochemical investigation of a MeOH extract of Centipeda minima led to the isolation of a sesquiterpene lactone, brevilin A, which was explored to elucidate potential anti-fibrotic effects by reversing HSC activation. First, we observed that transforming growth factor (TGF)-β1 treatment significantly increased the expression levels of HSC activation marker, α-smooth muscle actin (α-SMA), and ECM protein such as collagen and fibronectin. Then, we demonstrated that brevilin A reversed the TGF-β1-induced increase in protein and mRNA expression levels of α-SMA and collagen. To investigate the underlying molecular mechanism of brevilin A, we evaluated the effects of brevilin A on the STAT3 signaling pathway. STAT3 phosphorylation, increased by TGF-β1 treatment, was strongly inhibited by brevilin A; the expression levels of fibronectin and connective tissue growth factor were also significantly decreased by brevilin A. The present study indicated that brevilin A has a preventive and therapeutic potential against hepatic fibrosis.

• Authors: Yong Joo Park, Mi Seon Jeon, Seulah Lee, Jung Kyu Kim, Tae Su Jang, Kyu Hyuck Chung, Ki Hyun Kim
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 41 Pg. 127989 (06 01 2021) ISSN: 1464-3405 [Electronic] England
• PMID: 33794317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Crotonates
• STAT3 Transcription Factor
• STAT3 protein, human
• Sesquiterpenes
• brevilin A

Topics

• Crotonates (chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Design
• Hepatic Stellate Cells (drug effects)
• Humans
• Liver Cirrhosis (drug therapy, metabolism, pathology)
• Molecular Structure
• STAT3 Transcription Factor (antagonists & inhibitors, genetics, metabolism)
• Sesquiterpenes (chemistry, pharmacology)
• Signal Transduction (drug effects)
• Structure-Activity Relationship