Osthole 通过抑制 IL-31 的产生，改善 2,4-二氯硝基苯诱发的特应性皮炎的慢性瘙痒症状

IF 4.7 4区医学 Q1 CHEMISTRY, MEDICINAL

Chinese Herbal Medicines Pub Date : 2025-04-01 DOI:10.1016/j.chmed.2024.01.003

Shuang He , Xiaoling Liang , Weixiong Chen , Yangji Nima , Yi Li , Zihui Gu , Siyue Lai , Fei Zhong , Caixiong Qiu , Yuying Mo , Jiajun Tang , Guanyi Wu

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引用次数: 0

摘要

目的探讨蛇床子素治疗特应性皮炎（AD）的治疗潜力，重点探讨其缓解慢性瘙痒（CP）的能力及其分子机制。方法研究蛇蛇素对2,4-二氯硝基苯（DNCB）诱导的AD小鼠模型和肿瘤坏死因子-α (TNF-α)和干扰素-γ (IFN-γ)刺激的人永生化表皮（HaCaT）细胞的抗炎作用。在AD小鼠模型中特异性评价蛇床子的止痒作用。采用苏木精和伊红（HE）染色、酶联免疫吸附试验（ELISA）、免疫印迹（WB）、实时荧光定量PCR （qRT-PCR）和免疫荧光染色等方法。结果sosthole改善了ad样小鼠的皮肤损伤和临床皮炎评分，减少了抓伤次数，降低了表皮厚度。它还降低了皮肤组织和HaCaT细胞中白细胞介素(IL)-31和IL-31受体A （IL-31 RA）的水平。此外，蛇床子素抑制磷酸化p65 （p-p65）和磷酸化核因子κ b α (p- κ b α)的蛋白表达水平。同时提高HaCaT细胞过氧化物酶体增殖物激活受体α (PPARα)和PPARγ的蛋白表达水平。结论蛇床子素通过激活PPARα、PPARγ，抑制NF-κB信号通路，抑制IL-31、IL-31 RA的表达，有效抑制AD CP。

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Osthole ameliorates chronic pruritus in 2,4-dichloronitrobenzene-induced atopic dermatitis by inhibiting IL-31 production

Objective

This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms.

Methods

In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) stimulated huma immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining.

Results

Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Bα (p-IκBα). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor α (PPARα) and PPARγ in HaCaT cells.

Conclusion

These findings indicated that osthole effectively inhibited CP in AD by activating PPARα, PPARγ, repressing the NF-κB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

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来源期刊

Chinese Herbal Medicines CHEMISTRY, MEDICINAL-

CiteScore

4.40

自引率

5.30%

发文量

629

审稿时长

10 weeks

期刊介绍： Chinese Herbal Medicines is intended to disseminate the latest developments and research progress in traditional and herbal medical sciences to researchers, practitioners, academics and administrators worldwide in the field of traditional and herbal medicines. The journal's international coverage ensures that research and progress from all regions of the world are widely included. CHM is a core journal of Chinese science and technology. The journal entered into the ESCI database in 2017, and then was included in PMC, Scopus and other important international search systems. In 2019, CHM was successfully selected for the “China Science and Technology Journal Excellence Action Plan” project, which has markedly improved its international influence and industry popularity. CHM obtained the first impact factor of 3.8 in Journal Citation Reports (JCR) in 2023.