Abstract
Diabetic wounds are serious and challenging complications of diabetes mellitus (DM) and are characterized by impaired healing. Its pathogenesis is complex and involves a variety of physiological and pathological changes, including vascular dysfunction, neuropathy, impaired neuropeptide signaling, hyperglycemia, persistent infections, inflammation, oxidative stress, and an impaired immune response. Despite significant advances in the understanding of the pathogenesis of diabetic wounds, current treatment options remain limited and often yield unsatisfactory results. Thus, there is an urgent need for alternative approaches to enhance diabetic wound healing. Silymarin (SM) is a natural flavonolignans derived from the traditional medicinal plant Silybum marianum (L.) Gaertn, with silibinin/silybin (SB) as its primary active component, and has shown considerable therapeutic potential in both experimental and clinical studies. This review synthesizes high-quality, peer-reviewed research on the use of SM/SB for DM and its complications, and suggests that SM/SB may promote wound closure through its established anti-inflammatory, antioxidant, antidiabetic, hypoglycemic, neuroprotective, and vascular/endothelial-protective properties. In this review, we highlight the current beneficial modulatory effects of SM/SB on diabetic wounds and explore the potential mechanisms that may support these benefits. Although early evidence is promising, further high-quality clinical studies are needed to confirm the efficacy of SM/SB in diabetic wound healing. Additionally, advancements in biomaterials could enhance the in vivo efficacy of SM, accelerating the translation of SM/SB-based therapies into clinical practice and offering a novel, complementary treatment or an innovative alternative to conventional protocols for diabetic wound closure.