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-α-mediated production of interleukin (IL)-1β, 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-α-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.

中文翻译：

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Ar-Turmerone通过灭活刺猬通路在HaCaT角质形成细胞中发挥抗增殖和抗炎活性。

银屑病是一种常见的皮肤炎性疾病，其特征在于角质形成细胞的异常生长和分化。Ar-Turmerone是姜黄的主要生物活性成分，已被发现可缓解牛皮癣样小鼠的皮肤炎症。然而，ar-turmerone对角质形成细胞的作用及其潜在机制仍然未知。分别通过MTT，流式细胞术分析和ELISA研究了ar-turmerone单独或与重组人声波刺猬（rhShh）联合使用对细胞增殖，凋亡和炎性细胞因子分泌的影响。分别通过RT-qPCR和Western blot分析确定Shh，胶质母细胞瘤1（Gli1）和平滑肌（SMO）的mRNA和蛋白水平。结果显示，ar-turmerone剂量依赖性地抑制增殖，促进细胞凋亡，减少了HaCaT细胞中TNF-α介导的白介素（IL）-1β，IL-6和IL-8的产生。Ar-turmerone阻止了HaCaT细胞中的Hedgehog通路，这由Shh，Gli1和SMO的表达减少所证明。此外，rhShh对Hedgehog通路的激活消除了Ar-turmerone对HaCaT细胞中增殖，凋亡和TNF-α介导的炎性细胞因子表达的影响。总之，ar-turmerone通过灭活HaCaT细胞中的Hedgehog途径抑制细胞增殖能力并减弱炎症细胞因子的表达，有助于更好地了解ar-turmerone对牛皮癣的潜在抗银屑病作用。此外，rhShh对Hedgehog通路的激活消除了Ar-turmerone对HaCaT细胞中增殖，凋亡和TNF-α介导的炎性细胞因子表达的影响。总之，ar-turmerone通过灭活HaCaT细胞中的Hedgehog途径抑制细胞增殖能力并减弱炎症细胞因子的表达，有助于更好地了解ar-turmerone对牛皮癣的潜在抗银屑病作用。此外，rhShh对Hedgehog通路的激活消除了Ar-turmerone对HaCaT细胞中增殖，凋亡和TNF-α介导的炎性细胞因子表达的影响。总之，ar-turmerone通过灭活HaCaT细胞中的Hedgehog途径抑制细胞增殖能力并减弱炎症细胞因子的表达，有助于更好地了解ar-turmerone对牛皮癣的潜在抗银屑病作用。