<i>Capparis Spinosa</i> and Glutamine Reduce Oxidative Stress via Nrf2/Ho‐1 Pathway in Diabetic Wound Healing

Chronic diabetic wounds remain a major clinical challenge due to impaired healing processes driven by oxidative stress. This study evaluates the effects of Capparis spinosa and glutamine, administered individually or in combination, on diabetic wound healing with a focus on the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Forty-two adult male Wistar albino rats with streptozotocin (STZ)-induced diabetes and excisional wounds were allocated into seven groups: control, untreated, glutamine-treated, C. spinosa (topical and oral), and combined C. spinosa + glutamine (topical and oral). On day 7, wound tissues were analyzed for Nrf2, HO-1, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and collagen levels using ELISA. Oxidative stress markers, including malondialdehyde (MDA), nitric oxide (NOx), protein carbonyl (PC), glutathione (GSH), and ascorbic acid (AA), were measured spectrophotometrically, alongside morphological and histopathological evaluations. Combined treatment significantly decreased MDA, NOx, PC, MMP-2, and MMP-9 levels, while increasing GSH, AA, and collagen levels. These changes were associated with enhanced wound closure, reduced inflammation, and improved tissue remodeling. Both individual and combined treatments promoted Nrf2 activation and normalized HO-1 expression. Overall, C. spinosa and glutamine enhance diabetic wound repair by restoring redox balance and strengthening endogenous antioxidant defense mechanisms.