Apigenin alleviates inflammation as a natural IRAK4 inhibitor
文献类型：期刊论文
| 作者 | Gongpan, Pianchou1,10; Xu, Tingting7,8,9; Zhang, Yufei6; Ji, Kailong1; Kong, Lingmei5; Wang, Xue8,9; Chen, Hongman2; Song, Qishi1; Sun, Yili6,8,9; Geng, Chang-an10 |
| 刊名 | PHYTOMEDICINE
 |
| 出版日期 | 2025-04-01 |
| 卷号 | 139页码:12 |
| 关键词 | Apigenin IRAK4 inhibitor Anti-inflammation NF-kappa B MAPK pathways Ulcerative colitis |
| ISSN号 | 0944-7113 |
| DOI | 10.1016/j.phymed.2025.156519 |
| 英文摘要 | Background: Uncontrolled inflammation is a key factor in the development of many diseases, and targeting pivotal kinases involved in the inflammatory response, such as interleukin-1 receptor-associated kinase 4 (IRAK4), holds promise for the treatment of inflammatory conditions. Apigenin (Api) is a popular element in numerous plants, possessing anti-inflammatory properties. Many studies have shown that Api modulates NF-kappa B signaling and MAPK cascade to reduce inflammation, but the exact mechanisms by which Api regulates these pathways remain unclear. Purpose: The aim of this study was to investigate the role of Api on acute inflammation and its specific mechanism in mediating inflammation. Methods: The dextran sulfate sodium (DSS) induced ulcerative colitis (UC) model and LPS induced acute inflammation mouse model were established to investigate the anti-inflammatory effects of Api. Subsequently, the anti-inflammatory activity of Api was validated in vitro and vivo by RNA-seq, qPCR, Western blot, cytokine ELISA, immunofluorescence and histological analysis. A series of experiments were performed to study the effects of Api on IRAK4, including ADP-GloTM kinase assay, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), and molecular docking simulation. The targeting of Api to IRAK4 was verified by IRAK4 inhibitor and siRNA. Results: Oral administration of Api significantly ameliorated inflammatory conditions in the LPS induced acute inflammation and DSS induced UC mouse models. Furthermore, Api inhibited the expression of interleukin and chemotactic factor genes and downregulated the immune response of macrophages at the transcriptome level. Mechanistically, Api acted as a novel IRAK4 inhibitor, inhibiting kinase activity by direct binding to IRAK4 (Kd = 4.78 mu M) with an IC50 of 1.74 mu M, interfering with extracellular signaling to the NF-kappa B and MAPK pathways, and reducing the expression of pro-inflammatory factors in an IRAK4 dependent manner. Conclusion: In this study, Api was identified for the first time as a natural IRAK4 inhibitor that suppresses cytokine signaling pathways and modulates the immune response at the level of the transcriptome. The results provided valuable insights into the specific mechanism of Api inhibition of inflammatory activation and shed light on opportunities for the development of novel IRAK4 inhibitors based on Api, which is found in various plants. |
| WOS关键词 | COLITIS ; FAMILY |
| 资助项目 | Science Foundation of Shandong Province, China[ZR2024QC286] ; Key R&D Program of Shandong Province, China[2024CXPT028] ; Yunnan Provincial Postdoctoral Science Foundation |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001435115600001 |
| 出版者 | ELSEVIER GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316475]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Sun, Yili; Geng, Chang-an; Li, Jia |
| 作者单位 | 1.Chinese Acad Sci, CAS Key Lab Trop Plant Resources & Sustainable Use, Xishuangbanna Trop Bot Garden, Kunming 650223, Yunnan, Peoples R China 2.Yunnan Agr Univ, Coll Anim Sci & Technol, Kunming 650201, Yunnan, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Hangzhou 310000, Zhejiang, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China 5.Yunnan Univ, Sch Pharm, Key Lab Med Chem Nat Resource, Minist Educ, Kunming 650091, Yunnan, Peoples R China 6.Anhui Univ Chinese Med, Sch Pharm, Hefei 230012, Anhui, Peoples R China 7.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China 8.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264211, Shandong, Peoples R China 9.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 10.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Nat Med, Kunming 650201, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gongpan, Pianchou,Xu, Tingting,Zhang, Yufei,et al. Apigenin alleviates inflammation as a natural IRAK4 inhibitor[J]. PHYTOMEDICINE,2025,139:12. |
| APA | Gongpan, Pianchou.,Xu, Tingting.,Zhang, Yufei.,Ji, Kailong.,Kong, Lingmei.,...&Li, Jia.(2025).Apigenin alleviates inflammation as a natural IRAK4 inhibitor.PHYTOMEDICINE,139,12. |
| MLA | Gongpan, Pianchou,et al."Apigenin alleviates inflammation as a natural IRAK4 inhibitor".PHYTOMEDICINE 139(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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