o-Coumaric Acid Promotes Angiogenesis and Wound Healing Under Hyperglycemic Stress Through Modulation of Oxidative...

Diabetic wounds represent a clinical challenge due to delayed healing, excessive oxidative stress, chronic inflammation, and impaired angiogenesis. Existing therapeutic approaches are often associated with high costs, limited efficacy, and adverse effects, highlighting the need for safer and effective alternatives. o-Coumaric acid, a hydroxycinnamic acid derivative structurally related to several bioactive phenolics, remains relatively underexplored for diabetic wound management. This study investigated its pharmacokinetic profile, molecular interactions, and biological efficacy under hyperglycemic conditions. In silico molecular docking demonstrated favorable interactions with oxidative stress- and inflammation-related targets, with a binding energy of -7.92 kcal/mol. Computational ADME analysis predicted high gastrointestinal absorption and compliance with major drug-likeness parameters. In vitro antioxidant analyses showed 50% inhibition at 41.80 ± 0.26 µg/mL in DPPH and 40.19 ± 0.36 µg/mL in ABTS assays. The compound also inhibited α-glucosidase (18.93 ± 0.53 µg/mL) and α-amylase (30.16 ± 0.12 µg/mL), indicating antidiabetic potential. Functionally, o-coumaric acid enhanced cell migration (1.4-fold) and angiogenesis (3-fold), increased catalase and superoxide dismutase (SOD) activities (3.3- and 3.6-fold), reduced lipid peroxidation (1.7-fold), and modulated inflammatory cytokines by reducing TNF-α and IL-6 while restoring IL-10 expression. These findings suggest antioxidant, anti-inflammatory, and wound healing supportive effects under hyperglycemic conditions, warranting further in vivo validation.