A Comprehensive Review on the Role of Medicinal Plants in the Management of Diabetic Wound: A Mechanistic Insight

Background: Diabetes and its associated complications encompass a range of comorbidities, including issues like impaired wound healing and chronic ulceration. It is very important to find an effective and economical way to manage diabetes and its complications. This review seeks to outline the mechanisms of action and potential drug targets of specific medicinal plants and derived compounds in healing diabetic wounds. Additionally, it aims to offer scientific evidence and research insights for their clinical application. Methods: A literature search was conducted using Google Scholar, PubMed, and Scopus for articles on diabetic wound healing published between 2001 and December 2024. Using relevant keywords, 3122 articles were identified. After screening and applying exclusion criteria, 63 studies were selected and categorized into medicinal plants, plant-derived molecules, and clinical studies to explore potential therapeutic targets. Results: Chronic diabetic wounds (DW) exhibit impaired healing across all wound repair phases, i.e., hemostasis, inflammation, proliferation, and remodelling. During hemostasis, defective coagulation and impaired platelet aggregation delay initial wound closure. The inflammatory phase is characterized by persistent inflammation, driven by elevated pro-inflammatory cytokines (e.g., TNF-α, IL-6), reduced anti-inflammatory mediators, and dysregulated NF-κB, MAPK, and PI3K/Akt signalling pathways, which exacerbate tissue damage. In the proliferative phase, diminished levels of growth factors (e.g., VEGF, PDGF) and disrupted signalling cascades impair angiogenesis, fibroblast proliferation, and extracellular matrix (ECM) synthesis, hindering tissue regeneration. The remodelling phase is compromised by chronic inflammation and an imbalance in matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) activity, resulting in defective collagen reorganization, reduced tensile strength, and poor wound maturation. Herbal medicines demonstrate potential in ameliorating these impairments by modulating dysregulated pathways, exerting anti-inflammatory, antioxidant, and proangiogenic effects, and promoting balanced wound repair across all phases. Nevertheless, rigorous scientific validation and standardized documentation of traditional medicinal practices are essential to confirm their therapeutic efficacy and safety in DW management. Conclusion: Diabetic wound management remains a major clinical challenge due to the limited efficacy and side effects of standard therapies. Medicinal plants and their bioactive compounds show promising healing potential through multi-targeted mechanisms. This review highlights a key research gap in the mechanistic understanding and clinical validation of traditional remedies, offering novel insights into targeting pathways like NF-κB, MAPK, and PI3K/Akt for improved diabetic wound care.