Abstract
BACKGROUND: Impaired wound healing is a major complication in diabetic patients. Currently available wound therapies may cause adverse effects, highlighting the need for safer, natural alternatives. This study evaluated the wound healing potential of Uncaria callophylla Blume ex Korth. stem methanol extract (UCSME) in diabetic rats. METHODS: Diabetic excision wound models were established and animals were divided into six groups: non-diabetic untreated wounds, diabetic untreated wounds, diabetic wounds treated with UCSME ointment at concentrations of 5%, 10%, and 20%, and diabetic wounds treated with betadine ointment. Wound healing was assessed through wound area reduction, epithelialization time, inflammatory and proliferative cell counts, angiogenesis, collagen deposition, and hydroxyproline content. Phytochemical composition and antioxidant activity were also analyzed. RESULTS: UCSME ointment significantly accelerated wound closure, shortened epithelialization time, enhanced angiogenesis, re-epithelialization, collagen synthesis, and increased neutrophil, macrophage, and fibroblast counts compared to untreated diabetic controls (p < 0.05). A 5% concentration was sufficient to improve wound closure and proliferative cell responses, while 10% and 20% concentrations showed stronger effects on inflammatory response and angiogenesis. The 20% UCSME ointment produced the most pronounced improvements in angiogenesis, re-epithelialization, and hydroxyproline levels. UCSME contained high total phenolic (20.99%) and flavonoid (0.40%) contents and exhibited strong antioxidant activity (IC(50) = 16.06 ppm). LC-MS/MS and GC-MS analyses identified several bioactive compounds associated with wound healing and antioxidant effects. CONCLUSION: Topical UCSME effectively promotes wound healing in diabetic rats and represents a promising natural therapeutic candidate for diabetic wound management.