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大麻二酚通过抑制小鼠模型中的JAK2-STAT3减轻咪喹莫特诱导的银屑病

Cannabidiol Alleviates Imiquimod-Induced Psoriasis by Inhibiting JAK2-STAT3 in a Mouse Model.

作者信息

Kim Min-Seo, Lee Ji-Hyun, Kim Sae-Woong, Bang Chul-Hwan

机构信息

Department of Medical Sciences, Graduate School of The Catholic University of Korea, Seoul 06591, Republic of Korea.

Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

出版信息

Biomedicines. 2024 Sep 12;12(9):2084. doi: 10.3390/biomedicines12092084.

Abstract

Cannabidiol (CBD), a non-psychoactive compound from , has shown efficacy in treating psoriasis, a chronic inflammatory skin disease affecting 1-3% of the global population; however, the mechanisms remain unclear. This study investigated CBD's effects on imiquimod (IMQ)-induced psoriasis in mice, which were divided into five groups: Control, IMQ, Clobetasol, 0.01% CBD, and 0.1% CBD. After inducing psoriasis with IMQ, clobetasol or CBD was applied. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), with histopathological changes examined via hematoxylin and eosin staining. Gene expression of inflammatory markers (, , , , , and ) was analyzed by RT-PCR, while protein levels of signal transducer and activator of transcription (STAT)3, P-STAT3, Janus kinase (JAK)2, and JAK3 were evaluated through western blot and immunohistochemistry. The results demonstrated that CBD significantly reduced PASI scores, epidermal thickness, keratosis, hyperproliferation, and inflammation. Moreover, CBD inhibited the IL-23 receptor-mediated JAK2-STAT3 signaling pathway, leading to the downregulation of , , , , , and expression. These findings suggest that CBD effectively alleviates psoriasis-like symptoms in mice and may serve as a promising therapeutic agent for psoriasis by targeting the JAK2-STAT3 pathway.

摘要

大麻二酚(CBD)是一种源自大麻的非精神活性化合物,已显示出对银屑病有效的治疗作用。银屑病是一种慢性炎症性皮肤病,影响着全球1%-3%的人口;然而,其作用机制仍不清楚。本研究调查了CBD对咪喹莫特(IMQ)诱导的小鼠银屑病的影响,将小鼠分为五组:对照组、IMQ组、氯倍他索组、0.01%CBD组和0.1%CBD组。用IMQ诱导银屑病后,应用氯倍他索或CBD。使用银屑病面积和严重程度指数(PASI)评估银屑病严重程度,通过苏木精和伊红染色检查组织病理学变化。通过逆转录聚合酶链反应(RT-PCR)分析炎症标志物(白细胞介素-23(IL-23)、白细胞介素-17A(IL-17A)、白细胞介素-17F(IL-17F)、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)和白细胞介素-1β(IL-1β))的基因表达,同时通过蛋白质免疫印迹法和免疫组织化学评估信号转导和转录激活因子(STAT)3、磷酸化STAT3(P-STAT3)、Janus激酶(JAK)2和JAK3的蛋白水平。结果表明,CBD显著降低了PASI评分、表皮厚度、角化、过度增殖和炎症。此外,CBD抑制IL-23受体介导的JAK2-STAT3信号通路,导致IL-23、IL-17A、IL-17F、TNF-α、IFN-γ和IL-1β表达下调。这些发现表明,CBD可有效减轻小鼠银屑病样症状,通过靶向JAK2-STAT3通路可能成为一种有前景的银屑病治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bd/11428822/47d63a95df09/biomedicines-12-02084-g001.jpg

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