<![CDATA[Diabetes mellitus (DM) is conditionally defined by chronic high blood sugar, oxidative stress, and inflammation, with tumor necrosis factor (TNF) and peroxisome proliferator-activated receptor gamma (PPARγ) acting as critical therapeutic targets. This research investigated the phytochemical profile, antioxidant potential, and molecular pathways of Ruellia tuberosa L. leaf extract in relation to diabetes using a dual experimental and computational framework. The total phenolic content (TPC) and total flavonoid content (TFC) were quantified using Folin-Ciocalteu and aluminum chloride colorimetry assays, respectively, while antioxidant efficacy was assessed using the DPPH radical scavenging assay. Furthermore, a Network pharmacology approach incorporating target prediction, protein-protein interaction (PPI) analysis, and molecular docking was used to uncover multi-target interactions. Results showed a TPC of 34.14 mg GAE/g and a TFC of 4.949 ± 0.089 mg QE/g, with the extract demonstrating strong antioxidant activity (IC₅₀ = 83.96 ppm). Key bioactive compounds identified included β-sitosterol, stigmasterol, betulinic acid, apigenin, and luteolin. Computational docking revealed high binding affinity of β-sitosterol and stigmasterol toward TNF (-8.7 and -8.5 kcal/mol) and PPARγ (-10.2 and -9.8 kcal/mol). Network modeling identified 87 protein targets with TNF (0.79) and PPARγ (0.77) showing the highest centrality, emphasizing their significance in the extract's antidiabetic effects. This study provides molecular insights into the multi-target therapeutic potential of R. tuberosa L. leaf extract for diabetes treatment, addressing both inflammation and metabolic dysregulation.]]>
