Gynura procumbens Modulates VEGF Expression in Diabetic Wounds: Evidence from Immunohistochemistry and in silico Analysis

Background and Objective: Chronic hyperglycemia causes oxidative stress, immunological dysfunction and decreased angiogenesis, compromising wound healing. Wound healing requires VEGF, which stimulates angiogenesis and tissue regeneration. The aim of this study was to assess the effect of the ethanolic extract of Gynura procumbens leaves on VEGF expression in diabetic wound tissue using in vivo and in silico approaches. Materials and Methods: This study divided 30 alloxan-induced rats into five groups: Diabetic controls and those given Bioplacenton ointment and topical G. procumbens extract at 100, 200 and 300 mg/kg bw. Histology included hematoxylin-eosin staining and VEGF immunohistochemistry. The active chemicals of G. procumbens were examined using LC-MS/MS and VEGF was tested in silico utilizing molecular docking and dynamics. Data were analyzed using Kruskal-Wallis and Mann-Whitney tests, with results expressed as Mean±SD and significance set at p<0.05. Results: Gynura procumbens extract increased epithelial thickness, collagen density and balanced the number of fibroblasts in diabetic wounds, with the best results at a dose of 300 mg/kg body weight. VEGF expression increased significantly in group A3 compared to the untreated diabetic group. In silico tests showed that Mahuannin F had the highest binding affinity for VEGF (-7.2 kcal/mol) and was able to stabilize the VEGF structure disrupted by alloxan through hydrogen and hydrophobic interactions. Molecular dynamics simulations supported the conformational stabilization of VEGF by Mahuannin F. Conclusion: Diabetes wounds with topically administered G. procumbens extract had higher VEGF expression and better skin tissue architecture. Active substances like Mahuannin F, VEGF structural stabilizers, promote this chemical process.