Ferulic Acid Induces Keratin 6 alpha via Inhibition of Nuclear beta-Catenin Accumulation and Activation of Nrf2 in Wound-Induced Inflammation

Injured tissue triggers complex interactions through biological process associated with keratins. Rapid recovery is most important for protection against secondary infection and inflammatory pain. For rapid wound healing with minimal pain and side effects, shilajit has been used as an ayurvedic medicine. However, the mechanisms of rapid wound closure are unknown. Here, we found that shilajit induced wound closure in an acute wound model and induced migration in skin explant cultures through evaluation of transcriptomics via microarray testing. In addition, ferulic acid (FA), as a bioactive compound, induced migration via modulation of keratin 6 alpha (K6 alpha) and inhibition of beta-catenin in primary keratinocytes of skin explant culture and injured full-thickness skin, because accumulation of beta-catenin into the nucleus acts as a negative regulator and disturbs migration in human epidermal keratinocytes. Furthermore, FA alleviated wound-induced inflammation via activation of nuclear factor erythroid-2-related factor 2 (Nrf2) at the wound edge. These findings show that FA is a novel therapeutic agent for wound healing that acts via inhibition of beta-catenin in keratinocytes and by activation of Nrf2 in wound-induced inflammation.