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吴茱萸碱对小鼠银屑病皮损及瘙痒的抑制作用。

Inhibitory Effect of Evodiamine on Psoriasis Lesions and Itching in Mice.

作者信息

Liang Jianqiang, Chen Weixiong, Zhou Yanhui, Meng Weijia, Xie Man, Weng Yunying, Qin Luxuan, Li Jianmin, Wu Guanyi

机构信息

College of Basic Medicine, Guangxi University of Chinese Medicine, Nanning, People's Republic of China.

School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People's Republic of China.

出版信息

Clin Cosmet Investig Dermatol. 2024 Jun 25;17:1527-1541. doi: 10.2147/CCID.S462446. eCollection 2024.

DOI:10.2147/CCID.S462446
PMID:38948922
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11214558/
Abstract

PURPOSE

This study seeks to investigate the effect of evodiamine on psoriasis and psoriatic pruritus.

METHODS

Imiquimod-induced psoriasiform dermatitis in mice was used as a model, and evodiamine was topically applied for seven days. The mice were observed daily for skin damage on the back, clinical score and their scratching behavior was recorded. Blood samples were collected on the final day of the experiment, and the serum levels of pruritus-associated inflammatory cytokines tumor necrosis factor (TNF) -α, interleukin (IL) -23, and IL-17A were measured using enzyme-linked immunosorbent assay. Histopathological changes were observed in Hematoxylin and Eosin-stained skin specimens. The expression levels of transient receptor potential vanilloid (TRPV) 1, TRPV3, TRPV4, and the pruritus-related mediators Substance P (SP), nerve growth factor (NGF), and calcitonin gene-related peptide (CGRP) in the skin lesions were analyzed using Western blot and qRT-PCR. The effect of evodiamine on the exploratory behavior, motor, and coordination abilities of mice was assessed using open field, suspension, and Rota-Rod experiments. Molecular docking was utilized to verify the binding of evodiamine to the residues of TRPV1, TRPV3, and TRPV4.

RESULTS

Evodiamine reduced pruritus and inhibited inflammation by decreasing the levels of inflammatory mediators TNF-α, IL-23, and IL-17A in the serum of Imiquimod-induced mice and attenuated the mRNA and protein expression levels of SP, NGF, CGRP, TRPV1, TRPV3, and TRPV4 in the skin.

CONCLUSION

Evodiamine is an effective treatment for psoriasis and pruritus, due to its ability to inhibit immune inflammation and pruritic mediators.

摘要

目的

本研究旨在探讨吴茱萸碱对银屑病及银屑病瘙痒的影响。

方法

以咪喹莫特诱导的小鼠银屑病样皮炎为模型,局部应用吴茱萸碱7天。每天观察小鼠背部皮肤损伤情况,记录临床评分及搔抓行为。在实验最后一天采集血样,采用酶联免疫吸附测定法检测血清中与瘙痒相关的炎性细胞因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-23和IL-17A的水平。观察苏木精和伊红染色的皮肤标本的组织病理学变化。采用蛋白质免疫印迹法和定量逆转录-聚合酶链反应分析皮肤损伤中瞬时受体电位香草酸亚型(TRPV)1、TRPV3、TRPV4以及与瘙痒相关的介质P物质(SP)、神经生长因子(NGF)和降钙素基因相关肽(CGRP)的表达水平。采用旷场实验、悬尾实验和转棒实验评估吴茱萸碱对小鼠探索行为、运动和协调能力的影响。利用分子对接技术验证吴茱萸碱与TRPV1、TRPV3和TRPV4残基的结合。

结果

吴茱萸碱通过降低咪喹莫特诱导的小鼠血清中炎性介质TNF-α、IL-23和IL-17A的水平减轻瘙痒并抑制炎症,同时减弱皮肤中SP、NGF、CGRP、TRPV1、TRPV3和TRPV4的mRNA和蛋白表达水平。

结论

吴茱萸碱能够抑制免疫炎症和瘙痒介质,是治疗银屑病和瘙痒的有效药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/a639bacd798c/CCID-17-1527-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/9da8fb5dbcde/CCID-17-1527-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/9da014519f27/CCID-17-1527-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/0374b582f5f5/CCID-17-1527-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/2d97a1614676/CCID-17-1527-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/07f16494c5ae/CCID-17-1527-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/a639bacd798c/CCID-17-1527-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/9da8fb5dbcde/CCID-17-1527-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/d80f0619cfa4/CCID-17-1527-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/7fd89da175ef/CCID-17-1527-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/4d50c9cccd43/CCID-17-1527-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/9da014519f27/CCID-17-1527-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/0374b582f5f5/CCID-17-1527-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/2d97a1614676/CCID-17-1527-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/07f16494c5ae/CCID-17-1527-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51c7/11214558/a639bacd798c/CCID-17-1527-g0009.jpg

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TRPV1 and TRPA1 Channels Are Both Involved Downstream of Histamine-Induced Itch.TRPV1 和 TRPA1 通道均参与组胺诱导的瘙痒的下游反应。
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