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甘草查尔酮 A 通过靶向 Th17 细胞分化及角质形成细胞异常增殖缓解银屑病,其作用通路为 NF-κB 和 AP-1。

Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway.

机构信息

Medical College, Henan University of Chinese Medicine, Zhengzhou, China.

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Phytother Res. 2024 Jan;38(1):174-186. doi: 10.1002/ptr.8038. Epub 2023 Oct 17.

DOI:10.1002/ptr.8038
PMID:37849425
Abstract

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.

摘要

银屑病是一种常见的免疫介导的炎症性皮肤病,由角质形成细胞和免疫细胞之间的相互作用紊乱引起。中药在其治疗中显示出潜在的临床应用。甘草素是从甘草中提取的一种黄酮类化合物,具有潜在的镇咳、抗氧化和抗炎作用,因此可能具有治疗银屑病的潜力。本工作旨在探讨甘草素在治疗银屑病中的可能作用。用 TNF-α刺激 HaCaT 细胞,用或不用甘草素处理,通过 Western blot 和 RT-qPCR 进行分析,并收集细胞上清液,通过 ELISA 分析细胞因子。此外,还检查了 4 组小鼠:正常组、溶剂组、LQ-L 组和 LQ-H 组。6 天后处死小鼠,通过免疫组织化学、ELISA、RT-qPCR 和流式细胞术进行分析。结果表明,甘草素在体内外均能显著抑制银屑病的进展。甘草素强烈抑制 HaCaT 角质形成细胞的增殖,但不影响细胞活力。此外,甘草素减轻了咪喹莫特诱导的银屑病样皮肤炎症和体内 Th17 细胞和 DC 的积累。在 TNF-α诱导的 HaCaT 角质形成细胞中,炎症细胞因子的蛋白和 mRNA 表达水平均明显降低。在咪喹莫特诱导的小鼠中,甘草素处理后 NF-κB 和 AP-1 的激活减少。综上所述,我们的结果表明,甘草素可能通过调节 NF-κB 和 AP-1 信号通路作为银屑病的关键调节剂。

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