Forsythoside a as a potential therapeutic agent for non-alcoholic fatty liver disease: from target identification to in vitro and in vivo validation

Non-alcoholic fatty liver disease (NAFLD) is a long-term metabolic condition marked by unusual fat buildup in the liver, with an increasing occurrence worldwide. <i>Forsythoside A</i> (FA), a bioactive component of Forsythia suspensa, has anti-inflammatory, antioxidative, and hepatoprotective effects. This study investigates the mechanisms by which FA may treat NAFLD. Using bioinformatics tools, 35 potential targets of FA were identified, and a protein-protein interaction network was constructed. KEGG and GO enrichment analyses highlighted important pathways associated with NAFLD. The effects of FA were confirmed using both <i>in vitro</i> and <i>in vivo</i> NAFLD models. Matrix Metalloproteinase 9 (MMP9), and Tumour Necrosis Factor Alpha (TNFɑ), were identified as core targets. KEGG analysis showed that FA affects metabolic, TNF signalling, and insulin resistance pathways. <i>In vitro</i> and <i>in vivo</i>, FA reduced lipid accumulation and modulated TNFɑ, MMP9, and ALB expression. FA may treat NAFLD by modulating the TNFɑ/MMP9/ALB pathway, providing new therapeutic targets and insights for NAFLD treatment.