Natural product piperine alleviates experimental allergic encephalomyelitis in mice by targeting dihydroorotate dehydrogenase
文献类型：期刊论文
| 作者 | Liu, Zehui1; Hu, Qian1; Wang, Wanyan1; Lu, Sisi1; Wu, Dang1; Ze, Shuyin2,3; He, Jiacheng2,3; Huang, Ying4; Chen, Wuyan5; Xu, Yechun5
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| 刊名 | BIOCHEMICAL PHARMACOLOGY
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| 出版日期 | 2020-07-01 |
| 卷号 | 177页码:15 |
| 关键词 | Multiple sclerosis DHODH Piperine Natural product |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/j.bcp.2020.114000 |
| 通讯作者 | Lu, Weiqiang(wqlu@bio.ecnu.edu.cn) ; Huang, Jin(huangjin@ecust.edu.cn) |
| 英文摘要 | Multiple sclerosis (MS) is the most popular chronic and debilitating inflammatory disease of the central nervous system (CNS) that remains incurable. Dihydroorotate dehydrogenase (DHODH) is critical to the activity of T lymphocytes and represents a potential therapeutic target for MS. Here we identify piperine, a bioactive constituent of black pepper, as a potent inhibitor of DHODH with an IC50 value of 0.88 mu M. Isothermal titration calorimetry and thermofluor assay demonstrate the directly interaction between piperine and DHODH. The cocomplex crystal structure of DHODH and piperine at 1.98 angstrom resolution further reveal that Tyr356 residue of DHODH is crucial for piperine binding. Importantly, we show that piperine can inhibit T cell overactivation in a DHODH-dependent manner in concanavalin A-triggered T-cell assay and mixed lymphocyte reaction assay. Finally, piperine exhibits strong preventive and therapeutic effect in the MOG-induced experimental allergic encephalomyelitis (EAE), a useful model for studying potential treatments for MS, by restricting inflammatory cells infiltration into the CNS and preventing myelin destruction and blood-brain barrier (BBB) disruption. Taken together, these findings highlight DHODH as a therapeutic target for autoimmune disease of the nervous system, and demonstrate a novel role for piperine in the treatment of MS. |
| WOS关键词 | MULTIPLE-SCLEROSIS ; T-CELLS ; BLACK PEPPER ; INHIBITORS ; LEFLUNOMIDE ; DIFFERENTIATION ; TERIFLUNOMIDE ; BIOSYNTHESIS ; LYMPHOCYTES ; EXPRESSION |
| 资助项目 | National Natural Science Foundation of China[81773775] ; National Natural Science Foundation of China[81973362] ; National Natural Science Foundation of China[81972828] ; Shanghai Committee of Science and Technology[18431900500] ; Shanghai Committee of Science and Technology[19ZR1473500] ; Open Research Project of Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000541248000062 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/291843]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Lu, Weiqiang; Huang, Jin |
| 作者单位 | 1.East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China 2.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai, Peoples R China 3.East China Normal Univ, Sch Life Sci, Shanghai, Peoples R China 4.Guangdong Inst Drug Control, Guangzhou, Guangdong, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Zehui,Hu, Qian,Wang, Wanyan,et al. Natural product piperine alleviates experimental allergic encephalomyelitis in mice by targeting dihydroorotate dehydrogenase[J]. BIOCHEMICAL PHARMACOLOGY,2020,177:15. |
| APA | Liu, Zehui.,Hu, Qian.,Wang, Wanyan.,Lu, Sisi.,Wu, Dang.,...&Huang, Jin.(2020).Natural product piperine alleviates experimental allergic encephalomyelitis in mice by targeting dihydroorotate dehydrogenase.BIOCHEMICAL PHARMACOLOGY,177,15. |
| MLA | Liu, Zehui,et al."Natural product piperine alleviates experimental allergic encephalomyelitis in mice by targeting dihydroorotate dehydrogenase".BIOCHEMICAL PHARMACOLOGY 177(2020):15. |
入库方式： OAI收割
来源：上海药物研究所
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