Identification and mechanistic investigation of ellagitannins from Osbeckia octandra that attenuate liver fibrosis via the TGF-β/SMAD signaling pathway

ABSTRACT Fibrosis is a major problem in chronic liver disease with limited treatment options due to its complex nature. Herbal medicines are often used as an alternative. The aim of this study was to investigate the therapeutic potential of Osbeckia octandra and to identify its active compounds and regulatory pathways. The effects of crude leaf suspension and boiled leaf extract were investigated in an animal model, and the extract was found to be the more effective treatment. Three major bioactive compounds, pedunculagin, casuarinin, and gallic acid, were isolated from the extract using the hepatic stellate cell line, LX-2-based antifibrotic effect evaluation system. The results showed that all these compounds ameliorated LX-2 in fibrotic state. This inhibitory mechanism was confirmed through the TGF-β/SMAD signaling pathway. Collectively, the presence of these compounds in O. octandra suggests its potential as a treatment for liver fibrosis. Graphical Abstract Graphical Abstract LX-2 antifibrotic screening system found that Osbeckia octandra boiled leaf extract contains: pedunculagin, casuarinin, and gallic acid as the main therapeutic agents for liver fibrosis.