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. Forsythoside A (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 in vitro and in vivo 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. In vitro and in vivo, 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.