Proteomic analysis of 7-octenoic acid antifibrotic effects in TGF-β1 activated hepatic stellate cells

Abstract

Liver fibrosis represents the liver’s adaptive response to sustained and intense inflammation triggered by diverse insults, ranging from dietary factors to infectious agents. Although early-stage fibrosis can be reversible, unchecked progression often leads to cirrhosis and hepatocellular carcinoma. Therapeutic options remain limited, highlighting the pressing need for novel anti‑fibrotic agents. In this study, we evaluated the in vitro anti‑fibrotic effects of 7‑octenoic acid (7‑OCT), a bioactive constituent from Moringa oleifera Lam. Human hepatic stellate LX‑2 cells were stimulated with TGF‑β1 (10 ng/mL) in the presence or absence of 7‑OCT. Fibrotic marker expression was quantified at both the mRNA and protein levels. Comprehensive proteomic profiling and subsequent in silico docking analyses were performed to identify putative molecular targets and clarify mechanisms of action. Our results demonstrate that 7‑OCT significantly suppresses the expression of α‑smooth muscle actin (α‑SMA), collagen type I, and matrix metalloproteinase‑9 (MMP‑9) by downregulating transforming growth factor beta receptor 1 (TGFBR1) expression and inhibiting mothers against decapentaplegic homolog 3 (SMAD3) phosphorylation. Proteomic data implicates focal adhesion pathway proteins in mediating these effects. Collectively, these findings suggest that 7‑OCT is a promising lead compound for the development of anti‑fibrotic therapies. © The Author(s) 2025.