Abstract
Chronic low-grade inflammation is a key contributor to the pathogenesis and complications of diabetes, leading to issues such as joint pain, skin disorders, periodontal disease, and neuropathy. Therefore, targeting inflammatory pathways has emerged as a promising therapeutic strategy for both the prevention and management of diabetes and its associated comorbidities. Natural products with dual anti-inflammatory and antidiabetic properties have gained significant interest, with Scoparia dulcis showing notable therapeutic potential. This study aimed to evaluate the efficacy of this herbal medicine in alleviating inflammation in diabetic patients using an integrative in silico approach, incorporating network pharmacology, molecular docking, and molecular dynamics simulations. Initial screening of compounds focused on their ability to inhibit key pathological targets implicated in diabetes-related inflammation. Pathway enrichment analysis revealed significant involvement in the AGE-RAGE signaling pathway, lipid metabolism, atherosclerosis pathways, and the hypoxia-inducible factor 1 (HIF-1) pathway. Ten critical molecular targets were identified, with TNF-α being the most prominent. Molecular docking followed by 200 ns molecular dynamics simulations assessed the binding affinity of TNF-α with the top ten selected compounds, revealing strong and stable interactions with essential active site residues. Furthermore, ADMET analysis and density functional theory (DFT) evaluations highlighted the therapeutic potential of these compounds as promising lead candidates for drug development. Existing literature supports the antidiabetic effects of these bioactive compounds, reinforcing the in silico findings. Thus, Scoparia dulcis represents a potential adjunct or alternative therapy for diabetic patients with chronic inflammation, offering a multifaceted approach to disease management.