Cucurbitacin B inhibits Th17 cell differentiation via the suppression of the JAK/STAT pathway and alleviates collagen-induced arthritis in mice.

IF 3.5 3区医学

International Journal of Immunopathology and Pharmacology Pub Date : 2025-01-01 Epub Date: 2025-06-16 DOI:10.1177/03946320251348715

Shu-Ping Kung, Hira Umbreen, Jou-Hsuan Wang, Chih-Ming Tsia, Tim Chi-Chen Lin, Yu-Ting Chen

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Abstract

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease with limited treatment options and associated side effects or resistance. This study aims to investigate the therapeutic potential of the natural compound cucurbitacin B (CuB) in RA treatment.

Methods: We utilized a collagen-induced arthritis (CIA) mouse model to evaluate the effects of CuB. Arthritis scores, histological damage, and pro-inflammatory cytokine expression (TNF-α, IL-17A) were assessed. In addition, network pharmacology analysis was performed to explore CuB's molecular mechanisms, focusing on Th17 cell differentiation, IL-17 signaling, and the JAK-STAT pathway.

Results: CuB significantly reduced arthritis severity, decreased histological damage, and lowered the expression of pro-inflammatory cytokines in CIA mice. CuB was found to inhibit STAT3 phosphorylation and reduce the proportion of Th17 cells in the spleen, indicating its potential anti-inflammatory effects.

Conclusion: These findings suggest that cucurbitacin B may serve as a promising novel therapeutic agent for rheumatoid arthritis by targeting key inflammatory pathways.

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葫芦素B通过抑制JAK/STAT通路抑制Th17细胞分化，减轻小鼠胶原诱导的关节炎。

目的：类风湿关节炎（RA）是一种慢性自身免疫性疾病，治疗方案有限，并伴有相关的副作用或耐药性。本研究旨在探讨天然化合物葫芦素B （CuB）在类风湿关节炎中的治疗潜力。方法：采用胶原性关节炎（CIA）小鼠模型，评价幼崽的作用。评估关节炎评分、组织学损伤和促炎细胞因子表达（TNF-α、IL-17A）。此外，通过网络药理学分析探讨CuB的分子机制，重点关注Th17细胞分化、IL-17信号通路和JAK-STAT通路。结果：CuB显著降低CIA小鼠关节炎严重程度，减轻组织学损伤，降低促炎细胞因子表达。研究发现，CuB可抑制STAT3磷酸化，降低脾脏中Th17细胞的比例，提示其潜在的抗炎作用。结论：这些发现提示葫芦素B可能是一种有前景的新型类风湿关节炎治疗剂，通过靶向关键的炎症通路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Immunopathology and Pharmacology Immunology and Microbiology-Immunology

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期刊介绍： International Journal of Immunopathology and Pharmacology is an Open Access peer-reviewed journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The intention is that the journal should reflect both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.