Bioactive compounds from Tinospora cordifolia and Azadirachta indica could alleviate diabetic foot ulcers: A Systematic in-silico study of their effects on SIRT1, TGFBR1, F2, NOS3, and MAPK14 via signaling pathways

Diabetic foot ulcers (DFUs) are a complicated disease, often associated with high blood sugar levels. They significantly impact quality of life and incur substantial economic costs. In this systemic molecular docking study, we selected two plants with potential anti-diabetic and wound-healing properties: Tinospora cordifolia and Azadirachta indica. There are thirty-two compounds involved in physiological and toxicological parameters. We selected four compounds based on these parameters and compared them with moxifloxacin. The targeted hub genes were involved in several biological pathways, including relaxin signaling (FDR: 2.42E-08), AGE RAGE signaling in diabetic complications (FDR: 2.22E-05), VEGF signaling (FDR: 0.00425), IL-17 signaling (FDR: 1.17E-05), diabetic cardiomyopathy (FDR: 1.17E-05), platelet activation (FDR: 0.000834), and cellular senescence (FDR: 0.001207). Among the selected compounds, nimbidiol exhibited strong binding affinities against all selected compounds to all protein receptors, including SIRT1 (-7.43 kcal/mol), MAPK14 (-7.36 kcal/mol), F2 (-7.31 kcal/mol), NOS3 (-6.62 kcal/mol), and TGBR1 (-6.58 kcal/mol), compared to caulerpin, lactopiperanol c, phloretin, and moxifloxacin, making it a promising candidate. While caulerpin did exhibit some binding affinity, it was notably lower than that of nimbidiol. Additionally, lactopiperanol C and phloretin had stronger binding affinities to F2 and TGBR1 compared to moxifloxacin. Further, the efficacy and safety profiles of finalized molecule suggested through animal study.