α-Mangostin in Diabetic Wound Healing: Roles of Growth Factors and Endothelial Dysfunction

Abstract

Diabetic foot ulcers (DFUs) represent one of the most debilitating complications of diabetes mellitus, largely driven by impaired wound healing processes, endothelial dysfunction, and dysregulated growth factor activity. Normal wound repair is orchestrated by a coordinated sequence of cellular and molecular events involving macrophages, fibroblasts, and endothelial cells, with growth factors such as PDGF, VEGF, TGF-β, bFGF, and CTGF playing central roles. In diabetic conditions, however, hyperglycemia-induced oxidative stress, reduced nitric oxide availability, and chronic inflammation disrupt these pathways, leading to delayed angiogenesis and poor tissue regeneration. Natural products have emerged as promising alternatives for chronic wound management, owing to their antioxidant, anti-inflammatory, and pro-angiogenic properties. Among these, α-mangostin, the predominant xanthone in the mangosteen (Garcinia mangostana) pericarp, has demonstrated potent anti-inflammatory and proliferative effects in vitro, accelerating fibroblast migration and suppressing cytokines such as IL-6 and IL-8. While most studies to date have focused on normal wound models, evidence suggests that α-mangostin may also modulate endothelial function and growth factor signaling under diabetic conditions. This review synthesizes current knowledge on growth factor regulation, endothelial dysfunction, and the therapeutic potential of α-mangostin in diabetic wound healing. Understanding these mechanisms may provide a foundation for developing cost-effective, locally sourced, natural product-based therapies to reduce the clinical and economic burden of DFUs.