Topical application of <i>Solanum nigrum</i> ameliorate impaired wound healing associated with diabetes mellitus: A network pharmacology and experimental approach

Diabetes-related poor wound healing is a severe clinical challenge, causing prolonged morbidity, higher amputation risk, and high healthcare costs. Current treatment approaches are often inadequate, emphasizing the need for safe, cost-effective, multi-targeted therapies combating oxidative stress, inflammation, infection, and hyperglycemia. This study explored the diabetic wound healing potential of Solanum nigrum hydroalcoholic fruit extract (SNHE) and its molecular mechanisms employing experimental assays and network pharmacology analysis. The biological activities were evaluated using DPPH and ABTS radical scavenging tests, heat-induced red blood cell membrane stabilization for anti-inflammatory effects, α-amylase inhibition, and 2-NBDG glucose uptake in McCoy cells for antidiabetic activity. Antimicrobial efficacy was assessed using minimum inhibitory concentration (MIC) tests against Staphylococcus aureus , Bacillus subtilis , Escherichia coli , and Salmonella typhi , whereas fibroblast proliferation and migration were examined using MTT and wound-scratch assays. Zebrafish caudal-fin regeneration and streptozotocin-induced diabetic rat excision wound models were used to investigate in vivo activity. Network pharmacology was used to identify active chemicals, molecular targets, and pathways associated with diabetic foot ulcers, followed by molecular docking. SNHE demonstrated strong antioxidant properties (DPPH IC50 = 0.031 mg/mL; ABTS IC50 = 0.051 mg/mL), supressed α-amylase activity by 72.59%, enhanced glucose uptake by 245.2%, and inhibited hemolysis by 64.35%. The MIC values for SNHE ranged from 0.781–3.125 mg/mL, with the maximum sensitivity recorded for S. aureus . Effect of SNHE on McCoy cells migration resulted in 27.29% wound closure. In vivo , SNHE promoted 50.67% Zebrafish fin regeneration and 86.54% wound closure in diabetic rats. Network pharmacology revealed four active chemicals from S. nigrum —beta-ionone, ascorbic acid, citric acid, and nicotinamide—that interact with 117 DFU-related targets. Beta-ionone exhibited notable interactions with the key DFU genes AKT1, STAT3, PPARG, and PTGS2. Results suggest that S. nigrum has potential for enhancing diabetic wound healing, serving as both a useful systemic and topical therapy.