Exploring the Effects of <i>Pterocarpus Soyauxii</i> Against Menopause‐Related NAFLD Based on Network Pharmacology, Molecular Docking, and Experimental Validation

Pterocarpus soyauxii (P. soyauxii) is a Fabaceae family traditionally used to treat menopausal disorders. This study aims to investigate the effect of P. soyauxii on menopause-related non-alcoholic fatty liver disease (NAFLD) and to determine its mechanisms of action and signaling pathways. The pharmacokinetic and dynamic properties and the toxicological profile of P. soyauxii compounds were assessed using the SwissADME and Protox III databases. A pharmacology network was constructed to identify active compound targets and corresponding genes. Compound target and protein-protein interaction networks were created using Cytoscape software. Molecular docking studies were conducted to assess the binding affinity of P. soyauxii compounds with specific proteins. In vitro experiments evaluated the antioxidant properties of P. soyauxii. In vivo studies using ovariectomized (Ovx) rat models underlined pathways and effects of P. soyauxii on biochemical and histological features linked with NAFLD. Findings suggest that P. soyauxii compounds are readily absorbed through the intestine and exhibit a relatively low level of toxicity. Protein-protein interaction, compound-target networks, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed several pathways and target proteins of P. soyauxii compounds. Indeed, they target specific proteins such as estrogen receptor alpha/beta ERα/β, nicotinamide adenine dinucleotide phosphate oxidase (NADPH-O), epidermal growth factor receptor (EGFR), MAPK1, peroxisome proliferator-activated receptors alpha/gamma (PPARα/G), and HMG-CoA reductase. Molecular docking revealed that P. soyauxii compounds demonstrate high binding affinity to various proteins. In vitro, P. soyauxii inhibits the oxidative power of OH, H₂O₂, and NO. In vivo, P. soyauxii significantly (p < 0.01, p < 0.001, and p < 0.01, respectively) reduces ALAT (25.14%), hepatic cholesterol (15.27%), and malondialdehyde (MDA) (26.78%) levels at 200 mg/kg and prevents steatosis in the liver. These findings suggest that P. soyauxii may have a protective role against menopause-related NAFLD.