PMID- 32087232 OWN - NLM STAT- MEDLINE DCOM- 20200527 LR - 20200527 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 249 DP - 2020 May 15 TI - Early astragaloside IV administration attenuates experimental autoimmune encephalomyelitis in mice by suppressing the maturation and function of dendritic cells. PG - 117448 LID - S0024-3205(20)30196-X [pii] LID - 10.1016/j.lfs.2020.117448 [doi] AB - AIMS: Dendritic cells (DCs) actively participate in the pathogenesis of multiple sclerosis (MS), an autoimmune disease. Astragaloside IV (ASI), an active monomer isolated from the Chinese medicine Astragalus membranaceus, has a wide range of pharmacological effects. We aimed to elucidate the effects of ASI on the development of DCs in the early stage of MS/EAE. MAIN METHODS: The mice were administered with ASI (20 mg/kg) daily 3 days in advance of EAE induction and continuously until day 7 post-immunization. The effect of ASI on CD11c(+) DC cells from bone marrow (BMDCs) or the spleen of EAE mice at day 7 post-immunization were investigated respectively by flow cytometry, ELISA, western blot, real-time PCR and immunofluorescence. KEY FINDINGS: ASI administration in the early stage of EAE was demonstrated to delay the onset and alleviate the severity of the disease. ASI inhibited the maturation and the antigen presentation of DCs in spleen of EAE mice and LPS-stimulated BMDCs, as evidenced by decreased expressions of CD11c, CD86, CD40 and MHC II. Accordingly, DCs treated by ASI secreted less IL-6 and IL-12, and prevented the differentiation of CD4(+) T cells into Th1 and Th17 cells, which was probably through inhibiting the activation of NFkappaB and MAPKs signaling pathways. SIGNIFICANCE: Our results implicated the alleviative effect of early ASI administration on EAE might be mediated by suppressing the maturation and function of DCs. The novel findings may add to our knowledge of ASI in the potentially clinical treatment of MS. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Yang, Liu AU - Yang L AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Han, Xinyan AU - Han X AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Yuan, Jinfeng AU - Yuan J AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Xing, Faping AU - Xing F AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Hu, Zhixing AU - Hu Z AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Huang, Fei AU - Huang F AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Wu, Hui AU - Wu H AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Shi, Hailian AU - Shi H AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. FAU - Zhang, Ting AU - Zhang T AD - Classical Prescription Experimental Platform, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zhangtingdoctor@163.com. FAU - Wu, Xiaojun AU - Wu X AD - Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: xiaojunwu320@126.com. LA - eng PT - Journal Article DEP - 20200219 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Cytokines) RN - 0 (NF-kappa B) RN - 0 (Saponins) RN - 0 (Triterpenes) RN - 3A592W8XKE (astragaloside A) SB - IM MH - Animals MH - Coculture Techniques MH - Cytokines/biosynthesis MH - Dendritic Cells/cytology/*drug effects/metabolism MH - Encephalomyelitis, Autoimmune, Experimental/pathology/*prevention & control MH - Female MH - MAP Kinase Signaling System MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - Saponins/*administration & dosage/pharmacology MH - Severity of Illness Index MH - Triterpenes/*administration & dosage/pharmacology OTO - NOTNLM OT - Astragaloside IV OT - Dendritic cells OT - Experimental autoimmune encephalomyelitis OT - Maturation and function OT - Multiple sclerosis COIS- Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted. EDAT- 2020/02/23 06:00 MHDA- 2020/05/28 06:00 CRDT- 2020/02/23 06:00 PHST- 2019/11/29 00:00 [received] PHST- 2020/02/15 00:00 [revised] PHST- 2020/02/17 00:00 [accepted] PHST- 2020/02/23 06:00 [pubmed] PHST- 2020/05/28 06:00 [medline] PHST- 2020/02/23 06:00 [entrez] AID - S0024-3205(20)30196-X [pii] AID - 10.1016/j.lfs.2020.117448 [doi] PST - ppublish SO - Life Sci. 2020 May 15;249:117448. doi: 10.1016/j.lfs.2020.117448. Epub 2020 Feb 19.