Brassinosteroids Control the Inflammation, Oxidative Stress and Cell Migration Through the Control of Mitochondrial Function on Skin Regeneration

Introduction: Brassinosteroids (BRs) are the class of phytohormones with great importance in agriculture and potential diverse effects on human welfare, including skin disease treatment. In this sense, BRs are a promising tool for promoting skin regeneration. Aims: Therefore, the objective of the present work was to analyze the effect of BRs in wound repair, mainly the inflammatory and proliferative phases, and their influence on migratory abilities in human dermal fibroblasts (HDFa), and consequently understand the mitochondrial metabolism. Main methods: We measured nine natural and synthetic BRs for the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We further evaluated the migration activity in HDFa modeling promotion of wound closure after BRs exposure. In addition, we evaluated the 84 gene profiles linked to wound healing response using RT2 Profiler PCR Array and examined cellular bioenergetics using an extracellular flux analyzer. Key findings: Results showed that LPS-induced cells had around 10 % lower reactive oxygen species and nitric oxide accumulation when treated with some BRs compounds. HDFa treated with homobrassinolide-based and homocastasterone-based compounds resulted in the greatest migratory activity and presents the best results for mitochondrial responses. Significance: Together, these results provided strong evidence for BRs' ability to promote skin health, particularly through contributions to both reducing excessive oxidative stress and controlling the inflammation process resulting in the best HDFa cell migration through the control of mitochondrial function.