Yang Wendong, Lu Jiabin, Luo Peihua, Xu Zhifei, Yan Hao, Yang Bo, He Qiaojun, Zhou Jialin, Yang Xiaochun
Center for Drug Safety Evaluation and Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Nanhu Brain-Computer Interface Institute, Hangzhou, 311100, China.
Chin Med. 2025 Aug 21;20(1):130. doi: 10.1186/s13020-025-01176-0.
The JAK-STAT signaling pathway serves as a central regulator of diverse cellular processes encompassing proliferation, apoptosis, inflammation, and differentiation. Specifically, extracellular ligands such as interleukins, and colony-stimulating factors induce JAKs phosphorylation, subsequently triggering dimerization and nuclear translocation of STATs protein. In this way, the JAK-STAT pathway modulates target gene expression. Dysregulation of the JAK-STAT pathways has been implicated in the pathogenesis of multiple diseases, including inflammatory diseases, autoimmune diseases, malignant tumors. Therefore, JAK inhibitors have been considered promising therapeutic candidates with substantial clinical potential. While previous reviews have primarily focused on natural products targeting JAK-STAT signaling pathways for the specific disease application, this paper comprehensively collected 88 natural products demonstrating JAKs inhibitory activity across multiple pathological conditions. We mainly referenced nearly 20 years of literature from 2005 to 2025, comprising 294 different types of publications including review articles and research papers. Through systematic analysis of the compounds, we further classified these phytochemicals according to their structural characteristics (flavonoids, alkaloids, terpenoids) and molecular targets within the signaling cascades. This study provides novel insights into the pathophysiological relationships between diseases and JAK kinases, while offering valuable guidance for developing next-generation JAK inhibitors with improved therapeutic profiles.
JAK-STAT信号通路是多种细胞过程的核心调节因子,这些过程包括增殖、凋亡、炎症和分化。具体而言,白细胞介素和集落刺激因子等细胞外配体可诱导JAKs磷酸化,随后触发STATs蛋白的二聚化和核转位。通过这种方式,JAK-STAT通路调节靶基因表达。JAK-STAT通路的失调与多种疾病的发病机制有关,包括炎症性疾病、自身免疫性疾病和恶性肿瘤。因此,JAK抑制剂被认为是具有巨大临床潜力的有前景的治疗候选药物。虽然先前的综述主要关注针对特定疾病应用的靶向JAK-STAT信号通路的天然产物,但本文全面收集了88种在多种病理条件下具有JAKs抑制活性的天然产物。我们主要参考了2005年至2025年近20年的文献,包括294种不同类型的出版物,如综述文章和研究论文。通过对这些化合物的系统分析,我们根据其结构特征(黄酮类、生物碱类、萜类)和信号级联中的分子靶点对这些植物化学物质进行了进一步分类。本研究为疾病与JAK激酶之间的病理生理关系提供了新的见解,同时为开发具有更好治疗效果的下一代JAK抑制剂提供了有价值的指导。
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