芹菜素通过抑制CDK2/E2F2通路抑制银屑病角化细胞增生和炎症

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-06 DOI:10.1016/j.phymed.2025.156486

Abudureyimu Alimujiang , Yutong Kang , Wenjing Wei , Zehua Zhang , Yipeng Bai , Yong Zhu , Shixia Huo , Dengqiu Xu , Zhijian Li

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引用次数: 0

摘要

背景银屑病是一种持久的炎症性皮肤疾病，其特征是真皮和表皮中角质形成细胞的异常生长和免疫细胞的浸润。地金草（DJC）是清血丸（QXW）的重要成分，传统上用于治疗牛皮癣。虽然其临床疗效是公认的，但缺乏药理学和机制研究限制了ddc作为一种有效的、有科学依据的银屑病治疗方法的验证。目的研究芪散散和姜黄的抗银屑病活性，确定其最有效的成分，并阐明其作用机制。方法对咪喹莫特（IMQ）诱导的银屑病患者分别给予QXW或DJC治疗，采用银屑病面积及严重程度指数（PASI）、组织学分析、免疫组织化学、免疫荧光、RT-PCR、ELISA等方法评价疗效。此外，采用UPLC-QTOF/MS技术和脂多糖（LPS）诱导的人角质形成细胞（HaCaT）细胞鉴定DJC的主要活性成分。通过RNA测序、Western blotting、细胞周期分析和荧光素酶测定获得了机制见解。结果芪xw和DJC治疗组PASI评分、皮肤厚度、脾脏指数、炎症细胞浸润均显著降低。此外，QXW和DJC均可降低血清促炎细胞因子水平。ddc通过抑制角化细胞增生和炎症反应来缓解银屑病。UPLC-QTOF/MS分析和lps诱导的HaCaT细胞研究发现，芹菜素是DJC的主要活性化合物。转录组学分析、WB、细胞周期和荧光素酶分析显示，芹菜素通过调节CDK2/ e2f2介导的细胞周期和IL-17信号通路，减轻角化细胞过度增殖和炎症反应。结论本研究首次全面比较了芪散、姜黄、芹菜素的抗银屑病作用。研究结果表明，QXW和DJC的治疗作用主要归因于芹菜素，其通过抑制CDK2/E2F2信号通路发挥抗增殖作用。

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Apigenin suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting CDK2/E2F2 pathway

Background

Psoriasis is a long-lasting inflammatory skin condition marked by unusual growth of keratinocytes and infiltration of immune cells in the dermis and epidermis. Dijincao (DJC), a key component of Qing Xue Wan (QXW), is traditionally used to treat psoriasis. Although its clinical efficacy is well-recognized, the absence of pharmacological and mechanistic studies limits the validation of DJC as an effective and scientifically substantiated treatment for psoriasis.

Purpose

This study aimed to investigate the anti-psoriasis activity of QXW and DJC, identify their most effective constituents, and elucidate the underlying mechanisms of action.

Methods

Mice with imiquimod (IMQ)-induced psoriasis were treated with QXW or DJC, and the therapeutic effects were evaluated using the Psoriasis Area and Severity Index (PASI), histological analysis, immunohistochemistry, immunofluorescence, RT-PCR, and ELISA. Additionally, UPLC-QTOF/MS technology and lipopolysaccharide (LPS)-induced human keratinocytes (HaCaT) cells were employed to identify the main active components of DJC. Mechanistic insights were gained through RNA sequencing, Western blotting, cell cycle analysis, and luciferase assays.

Results

Treatment with QXW and DJC resulted in a significant reduction of the PASI score, skin thickness, spleen index, and inflammatory cell infiltration. Moreover, both QXW and DJC reduced serum levels of pro-inflammatory cytokines. DJC alleviated psoriasis by inhibiting keratinocyte hyperproliferation and the inflammatory response. UPLC-QTOF/MS analysis and LPS-induced HaCaT cell studies identified Apigenin as the principal active compound of DJC. Transcriptomic analysis, along with WB, cell cycle, and luciferase assays, revealed that Apigenin mitigates keratinocyte hyperproliferation and the inflammatory response by modulating the CDK2/E2F2-mediated cell cycle and IL-17 signaling pathway.

Conclusion

This study represents the first comprehensive comparison of the anti-psoriatic effects of QXW, DJC, and Apigenin. The findings suggest that the therapeutic effects of QXW and DJC are primarily attributed to Apigenin, which exerts anti-proliferative properties by inhibiting the CDK2/E2F2 signaling pathway.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.