Natural Polyphenols as Multi-Targeted Agents in Diabetic Foot Ulcer: A Comprehensive Systematic Review
Abstract
Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes
mellitus, with a prevalence of 4–10% and a high risk of infection and limb amputation. This review
explores the therapeutic potential of polyphenols, plant-derived secondary metabolites, in
promoting wound healing in DFUs.
A systematic literature review was conducted in accordance with the PRISMA
guidelines. Databases including PubMed, ISI Web of Knowledge, Google Scholar, and Scopus
were searched for relevant studies from 1999 to 2025. Articles evaluating polyphenol-rich
medicinal plants and their role in diabetic wound healing were selected based on defined inclusion
and exclusion criteria.
Polyphenols such as curcumin, quercetin, gallic acid, resveratrol, and kaempferol
demonstrated strong antioxidant, anti-inflammatory, and pro-angiogenic properties. These
compounds modulate key molecular pathways—including VEGF, TGF-β, and NF-κB—resulting in
enhanced fibroblast proliferation, collagen synthesis, and tissue regeneration. Plants like Curcuma
longa, Punica granatum, and Vitis vinifera showed promising efficacy in both preclinical and
limited clinical studies.
The evidence highlights the multi-targeted actions of polyphenols in addressing the
impaired wound healing typical of diabetic conditions. However, limitations include variability in
bioavailability, formulation inconsistencies, and a lack of standardized clinical trials.
Polyphenols offer a promising, natural approach to managing DFUs,…
How strong is the evidence?
Evidence Hub reads this as a systematic review. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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