Wound healing properties of flavonoids: A systematic review highlighting the mechanisms of action

Background: Flavonoids are a class of compounds with a wide variety of biological functions, being an important source of new products with pharmaceutical potential, including treatment of skin wounds. Purpose: This review aimed to summarize and evaluate the evidence in the literature in respect of the healing properties of flavonoids on skin wounds in animal models. Study design: This is a systematic review following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Methods: This was carried out through a specialized search of four databases: PubMed, Scopus, Web of Science and Embase. The following keyword combinations were used: flavonoidal OR flavonoid OR flavonoidic OR flavonoids AND wound healing as well as MeSH terms, Emtree terms and free-text words. Results: Fifty-five (55) articles met the established inclusion and exclusion criteria. Flavonoids presented effects in respect of the inflammatory process, angiogenesis, re-epithelialization and oxidative stress. They were shown to be able to act on macrophages, fibroblasts and endothelial cells by mediating the release and expression of TGF-beta 1, VEGF, Ang, Tie, Smad 2 and 3, and IL-10. Moreover, they were able to reduce the release of inflammatory cytokines, NF kappa B, ROS and the M1 phenotype. Flavonoids acted by positively regulating MMPs 2, 8, 9 and 13, and the Ras/Raf/MEK/ERK, PI3K/Akt and NO pathways. Conclusion: Flavonoids are useful tools in the development of therapies to treat skin lesions, and our review provides a scientific basis for future basic and translational research.

Automated summary

Flavonoids have shown positive effects on skin wound healing in animal models by modulating the inflammatory process, angiogenesis, re-epithelialization, and oxidative stress. They interact with various cells and molecular pathways involved in wound healing, making them promising candidates for the development of skin lesion therapies.