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

Mikaella T B Carvalho; Heitor G Araújo-Filho; André S Barreto; Lucindo J Quintans-Júnior; Jullyana S S Quintans; Rosana S S Barreto

doi:10.1016/j.phymed.2021.153636

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

Phytomedicine. 2021 Sep:90:153636. doi: 10.1016/j.phymed.2021.153636. Epub 2021 Jun 19.

Authors

Mikaella T B Carvalho¹, Heitor G Araújo-Filho², André S Barreto³, Lucindo J Quintans-Júnior¹, Jullyana S S Quintans¹, Rosana S S Barreto⁴

Affiliations

¹ Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe, Marechal Rondon Avenue, S/N, Rosa Elza, CEP: 49.000-100, São Cristóvão, SE, Brazil; Health Sciences Graduate Program (PPGCS), Federal University of Sergipe, São Cristóvão, SE, Brazil.
² Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe, Marechal Rondon Avenue, S/N, Rosa Elza, CEP: 49.000-100, São Cristóvão, SE, Brazil.
³ Health Sciences Graduate Program (PPGCS), Federal University of Sergipe, São Cristóvão, SE, Brazil; Laboratory Pharmacology Cardiovascular (LAFAC), Department of Physiology, Federal University of Sergipe, São Cristóvão, SE, Brazil.
⁴ Laboratory of Neuroscience and Pharmacological Assays (LANEF), Department of Physiology, Federal University of Sergipe, Marechal Rondon Avenue, S/N, Rosa Elza, CEP: 49.000-100, São Cristóvão, SE, Brazil; Health Sciences Graduate Program (PPGCS), Federal University of Sergipe, São Cristóvão, SE, Brazil. Electronic address: rosanasbarreto@pq.cnpq.br.

PMID: 34333340
DOI: 10.1016/j.phymed.2021.153636

Abstract

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-β1, VEGF, Ang, Tie, Smad 2 and 3, and IL-10. Moreover, they were able to reduce the release of inflammatory cytokines, NFκB, 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.

Keywords: Chronic wounds; Flavonoids; Natural products; Skin lesions; Wound healing.

Publication types

Systematic Review

MeSH terms

Animals
Cytokines
Endothelial Cells
Fibroblasts
Flavonoids* / pharmacology
Macrophages
Signal Transduction
Wound Healing*

Substances

Cytokines
Flavonoids