Ar-Turmerone Exerts Anti-proliferative and Anti-inflammatory Activities in HaCaT Keratinocytes by Inactivating Hedgehog Pathway

Psoriasis, a common skin inflammatory disorder, is characterized by the aberrant growth and differentiation of keratinocytes. Ar-Turmerone, a main bioactive ingredient of Curcuma longa, has been found to alleviate skin inflammation in psoriasis-like mice. However, the effects and underlying mechanism of ar-turmerone on keratinocytes remain unknown. The effects of ar-turmerone alone or combined with recombinant human sonic hedgehog (rhShh) on cell proliferation, apoptosis, and inflammatory cytokine secretion were explored by MTT, flow cytometry analysis, and ELISA, respectively. The mRNA and protein levels of Shh, glioblastoma-1 (Gli1), and smoothened (SMO) were determined by RT-qPCR and western blot analysis, respectively. Results disclosed that ar-turmerone dose-dependently suppressed proliferation, facilitated apoptosis, and reduced TNF-alpha-mediated production of interleukin (IL)-1 beta, IL-6, and IL-8 in HaCaT cells. Ar-turmerone blocked Hedgehog pathway in HaCaT cells, as evidenced by the reduced expression of Shh, Gli1, and SMO. Moreover, activation of the Hedgehog pathway by rhShh abolished the effects of ar-turmerone on the proliferation, apoptosis, and TNF-alpha-mediated inflammatory cytokine expression in HaCaT cells. In conclusion, ar-turmerone suppressed cell proliferative ability and attenuated inflammatory cytokine expression by inactivating Hedgehog pathway in HaCaT cells, contributing to better understanding the potential anti-psoriasis effects of ar-turmerone on psoriasis.