trans-Cinnamic acid, but not p-coumaric acid or methyl cinnamate, induces fibroblast migration through PKA- and p38-MAPK signalling pathways.

AIM: Hydroxycinnamic acids their derivatives have various pharmacological properties. The hydroxycinnamic acid derivatives, methyl cinnamate, trans-cinnamic, and p-coumaric acids have been the object of study in the treatment of skin wounds. 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. MATERIALS AND METHODS: NIH 3T3 and L929 fibroblast cell lines were exposed to each drug at several concentrations and the effect on cell viability, cell cycle, and extracellular matrix production were assessed by MTT assay, flow cytometry, and immunofluorescence staining, respectively. The effect on cell migration was examined using scratch assay. RESULTS: The results showed that hydroxycinnamic acid derivatives not affect cell viability, but 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. The cell proliferation inhibitor mitomycin C abolished the effect induced by p-coumaric acid and methyl cinnamate, indicating that only the trans-cinnamic acid stimulated migration. A transwell migration assay confirmed that trans-cinnamic acid-treated fibroblasts exhibited increased migration compared with untreated cells. trans-Cinnamic acid-induced fibroblast migration was decreased by PKA inhibitor and p38-MAPK inhibitor but not by JNK inhibitor. Additionally, trans-cinnamic acid-treated fibroblasts showed an increase in the production of laminin and collagen type I. CONCLUSION: Our study showed that trans-cinnamic acid improves fibroblast migration and modulates extracellular matrix synthesis, indicating its potential for accelerating the healing process.

Effect of trans-cinnamic acid and p-coumaric acid on fibroblast motility: a pilot comparative study of in silico lipophilicity measure.

Cinnamic acids and their derivatives are found in abundance in fruits, vegetables, and other food products of plant origin. The trans-cinnamic and p-coumaric acids in particular have been a subject of research for the treatment of a diverse range of pathological conditions. However, it is unclear whether these derivatives exert a direct beneficial effect on the cells that play a role in regulating skin wound healing, such as fibroblasts. In this study, using in vitro scratch-wound healing assay, it was observed that treatment with trans-cinnamic acid resulted in increased migration of fibroblasts when compared with that of p-coumaric acid-treated cells, without any adverse effect on cell viability. Studies on the lipophilicity of these acids using the XLOGP3 algorithm showed that trans-cinnamic acid was more lipophilic than p-coumaric. Thus, the findings of this study indicated that the lipophilic characteristic of trans-cinnamic acid rendered it more suitable as a potential drug candidate.