Efeito dos ácidos trans-cinâmico, p-cumárico e cinamato de metila, sobre a migração de fibroblastos in vitro

Abstract

Hydroxycinnamic acids are found in abundance in fruits and other foods of plant origin. Their derivatives, methyl cinnamate, trans-cinnamic, and p-coumaric acids are present in several medicinal plants that have been the object of study in the treatment of distinct pathological conditions, including skin wounds. Several medicinal properties of hydroxycinnamic acid derivatives such as its antioxidant, anti-inflammatory, and healing effects have been reported in literature. However, it is unclear whether these derivatives exert a direct beneficial effect on fibroblast function. In this study, we evaluated the effects of methyl cinnamate, trans-cinnamic, and p-coumaric acids on fibroblast migration in vitro. The results showed that hydroxycinnamic acid derivatives not only affect cell viability, but also increase fibroblast migration in the in vitro scratch-wound healing assay. They also induced an increase in S and G2/M phases accompanied by a decrease in the G0/G1 phase of the cell cycle. To differentiate between proliferation and migration, fibroblasts were treated with mitomycin C and subjected to the scratch assay. This treatment abolished the effect induced by p-coumaric acid and methyl cinnamate, showing that only the trans-cinnamic acid stimulated the migration. trans-cinnamic acid induced fibroblast migration was decreased by PKA inhibitor (6-22-amide) and p38-MAPK inhibitor (SB203580) but not by JNK inhibitor (JNK-IN-8). Additionally, trans-cinnamic acid-treated fibroblasts showed na increase in the production of laminin and collagen type I, and a reduction in the production of fibronectin. Our study showed that trans-cinnamic acid improves fibroblast migration and modulates extracellular matrix synthesis, indicating its potential for accelerating the healing process