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

机译:大麻二酚通过在小鼠模型中抑制 JAK2-STAT3 来减轻咪喹莫特诱导的银屑病

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摘要

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, 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 (Il1b, Il6, Il12b, Il17a, Il22, and Tnf) 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 Il1b, Il6, Il12b, Il17a, Il22, and Tnf 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.
机译:大麻二酚 (CBD) 是一种来自大麻的非精神活性化合物,已显示出治疗银屑病的功效,银屑病是一种影响全球 1-3% 人口的慢性炎症性皮肤病;然而,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,小鼠分为五组:对照组、IMQ、氯倍他索、0.01% CBD 和 0.1% CBD。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,并通过苏木精和伊红染色检查组织病理学变化。通过 RT-PCR 分析炎症标志物 (Il1b 、 Il6 、 Il12b 、 Il17a 、 Il22 和 Tnf ) 的基因表达,同时通过蛋白质印迹和免疫组织化学评估信号转导和转录激活因子 (STAT)3 、 P-STAT3 、 Janus 激酶 (JAK) 2 和 JAK3 的蛋白质水平。结果表明,CBD 显着降低了 PASI 评分、表皮厚度、角化病、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Il1b、Il6、Il12b、Il17a、Il22和Tnf表达下调。这些发现表明,CBD有效地缓解了小鼠的银屑病样症状,并可能通过靶向JAK2-STAT3途径作为一种有前途的银屑病治疗剂。

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