Abstract
Background: The Malayali tribes of the Eastern Ghats, possess knowledge on medicinal plants for treating dermatological disorders. Notably, Andrographis paniculata, Aristolochia indica, Chloroxylon swietenia, Commiphora caudata, and Tridax procumbens are commonly used for dermatological management. This study aimed to scientifically validate the traditional wound-healing claims of these plants through phytochemical profiling, network pharmacology, molecular docking, and in vivo excision wound models. Materials and methods: Hydroalcoholic leaf extracts of the five plants were profiled using LC-QTOF-MS to identify major phytoconstituents. Network pharmacology was applied to predict compound–target interactions and enriched signaling pathways, followed by molecular docking to assess binding affinities with key inflammatory mediators. Wound-healing efficacy was evaluated in Wistar rats using excision wound models, with wound contraction, histopathology, and serum cytokine profiling (Tumour Necrosis Factor alpha, Interleukin 6 & 8) assessed over 24 days. Results: “LC-QTOF-MS analysis identified diverse bioactive compounds including andrographolide, neoandrographolide, aristolindiquinone, and apigenin derivatives”. Network pharmacology predicted 286 targets, highlighting Tumour Necrosis Factor alpha, Interleukin 6, Albumin, STAT3, and MAPK3 as key nodes enriched in TNF-α, PI3K–Akt, VEGF, FoxO, and Toll-like receptor signaling pathways. Molecular docking confirmed strong binding affinities with TNF-α, IL6, and ALB. The stability of the top-performing protein–ligand complexes was further validated by 100 ns molecular dynamics simulations, where Rutamarin, Neoandrographolide, and Silver sulfadiazine exhibited stable conformational behavior, persistent intermolecular interactions, and favorable MM/PBSA binding free energies, confirming their strong binding affinity and structural stability. In vivo, no dermal irritation was observed, and extract-treated groups showed accelerated wound contraction, complete epithelial restoration, and downregulation of pro-inflammatory cytokines compared to controls. Aristolochia indica and Chloroxylon swietenia extracts, particularly at higher doses, exhibited superior healing efficacy. Conclusion: This study reveals, for the first time, the wound-healing potential of Chloroxylon swietenia and Commiphora caudata, elucidating multi-target mechanisms of Malayali tribal plants and underscoring their ethnopharmacological significance as safe, plant-based alternatives to synthetic wound-healing agents, with strong potential for development as sustainable industrial crops for dermatological and wound-care product applications.