Cimifugin ameliorates imiquimod-induced psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway
Cimifugin ameliorates imiquimod-induced psoriasis by inhibiting oxidative stress and inflammation via NF-κB/MAPK pathway
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Cimifugin 通过 NF-κB/MAPK 通路抑制氧化应激和炎症，改善咪喹莫特诱导的牛皮癣
DOI：
10.1042/bsr20200471
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发表时间：
2020-06-17
影响因子：
4
通讯作者：
Wang, Qingxing
中科院分区：
文献类型：
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作者：
Liu, Aimin;Zhao, Wei;Wang, Qingxing
摘要 Cimifugin 是防风干燥根中色酮的重要成分，用于治疗炎症性疾病。然而，升麻新对银屑病的可能作用需要进一步研究。目前的工作旨在评估升麻净在体内和体外对银屑病的作用，并揭示其潜在的分子机制。在这里，我们使用咪喹莫特 (IMQ) 或肿瘤坏死因子 (TNF)-α 在小鼠或角质形成细胞中诱导银屑病样模型。显然，结果表明，西米夫净减少了 IMQ 诱导小鼠的表皮增生、银屑病面积严重指数 (PASI) 评分、耳朵厚度和组织学银屑病样病变。 IMQ 降低的还原型谷胱甘肽 (GSH)、超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 水平以及皮肤组织中丙二醛 (MDA) 的积累均被升麻净减弱。此外，还观察到 cimifugin 有效逆转 IMQ 诱导的促炎细胞因子的上调，包括 TNF-α、IL-6、IL-1β、IL-17A 和 IL-22。从机械角度来看，我们注意到 cimifugin 抑制 IMQ 激活的 NF-κB（IκB 和 p65）和 MAPK（JNK、ERK 和 p38）信号通路的磷酸化。在 TNF-α 处理的 HaCaT 细胞中也检测到氧化应激和炎症参数的类似变化。此外，在 TNF-α 处理的细胞中观察到 cimifugin 诱导的 ICAM-1 下调。总而言之，我们的研究结果表明，西米夫净通过灭活 NF-κB/MAPK 信号通路来防止银屑病样发病机制中的氧化应激和炎症，这可能会开发出一种治疗银屑病的新型有效药物。
Abstract Cimifugin is an important component of chromones in the dry roots of Saposhikovia divaricata for treating inflammatory diseases. However, the possible effect of cimifugin in psoriasis needs further investigation. This current work was designed to evaluate the effects of cimifugin in psoriasis in vivo and in vitro, and unravel the underlying molecular mechanism. Here, we used imiquimod (IMQ) or tumor necrosis factor (TNF)-α to induce a psoriasis-like model in mice or keratinocytes. Obviously, the results showed that cimifugin reduced epidermal hyperplasia, psoriasis area severity index (PASI) scores, ear thickness and histological psoriasiform lesions in IMQ-induced mice. The decreased levels of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and the accumulation of malondialdehyde (MDA) in skin tissues by IMQ were attenuated by cimifugin. Furthermore, it was observed that cimifugin effectively reversed IMQ-induced up-regulation of proinflammatory cytokines, including TNF-α, IL-6, IL-1β, IL-17A, and IL-22. Mechanically, we noticed that cimifugin inhibited IMQ-activated phosphorylation of NF-κB (IκB and p65) and MAPK (JNK, ERK, and p38) signaling pathways. Similar alterations for oxidative stress and inflammation parameters were also detected in TNF-α-treated HaCaT cells. In addition, cimifugin-induced down-regulation of ICAM-1 were observed in TNF-α-treated cells. Altogether, our findings suggest that cimifugin protects against oxidative stress and inflammation in psoriasis-like pathogenesis by inactivating NF-κB/MAPK signaling pathway, which may develop a novel and effective drug for the therapy of psoriasis.