PMID- 33362775 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20240330 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Bixin Attenuates Experimental Autoimmune Encephalomyelitis by Suppressing TXNIP/NLRP3 Inflammasome Activity and Activating NRF2 Signaling. PG - 593368 LID - 10.3389/fimmu.2020.593368 [doi] LID - 593368 AB - Multiple sclerosis (MS), an autoimmune and degenerative disease, is characterized by demyelination and chronic neuroinflammation. Bixin is a carotenoid isolated from the seeds of Bixa orellana that exhibits various potent pharmacological activities, including antioxidant, anti-inflammatory, and anti-tumor properties. However, the effects of bixin on MS have not yet been examined. To evaluate the effects and underlying molecular mechanisms of bixin on MS, experimental autoimmune encephalomyelitis (EAE) was established in C57BL/6 mice, which were treated via intragastric administration of bixin solutions. To evaluate the molecular mechanisms of bixin, quantitative reverse-transcription PCR, western blot, immunohistochemistry, flow cytometry, and enzyme-linked immunosorbent assay analyses were performed. We found that bixin significantly improved the symptoms and pathology in EAE mice, reduced the release of inflammatory cytokines TNF-alpha, IL-6, IL-8, IL-17, and IFN-gamma, and increased the expression of the anti-inflammatory cytokine IL-10. And bixin reduced the proportion of Th1 and Th17 cells in the spleen and CNS, and suppressed microglia aggregation, and TXNIP/NLRP3 inflammasome activity by scavenging excessive reactive oxygen species (ROS) in EAE mice. Furthermore, bixin inhibited inflammation and oxidative stress via activating nuclear factor erythroid 2-related factor 2 (NRF2), and its downstream genes in EAE mice, meanwhile, these effects were suppressed upon treatment with an NRF2 inhibitor, ML385. Bixin prevented neuroinflammation and demyelination in EAE mice primarily by scavenging ROS through activation of the NRF2 signaling pathway. Taken together, our results indicate that bixin is a promising therapeutic candidate for treatment of MS. CI - Copyright (c) 2020 Yu, Wu, Li, Deng, Liu, Zhang, He, Zhao and Xu. FAU - Yu, Ye AU - Yu Y AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - Wu, Dong-Ming AU - Wu DM AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - Li, Jing AU - Li J AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - Deng, Shi-Hua AU - Deng SH AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - Liu, Teng AU - Liu T AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - Zhang, Ting AU - Zhang T AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - He, Miao AU - He M AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - Zhao, Yang-Yang AU - Zhao YY AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. FAU - Xu, Ying AU - Xu Y AD - Clinical Medical College, The First Affiliated Hospital, Collaborative Innovation Center of Sichuan for Elderly Care and Health of Chengdu Medical College, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201209 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Carrier Proteins) RN - 0 (Cytokines) RN - 0 (Inflammasomes) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Reactive Oxygen Species) RN - 0 (Txnip protein, mouse) RN - 36-88-4 (Carotenoids) RN - 52500-60-4 (Thioredoxins) RN - 9L7T4VB66G (bixin) SB - IM MH - Animals MH - Carotenoids/chemistry/*pharmacology MH - Carrier Proteins/*metabolism MH - Cytokines/metabolism MH - Demyelinating Diseases/drug therapy/etiology/metabolism/pathology MH - Disease Models, Animal MH - Disease Susceptibility MH - Encephalomyelitis, Autoimmune, Experimental/drug therapy/*etiology/*metabolism/pathology MH - Female MH - Inflammasomes/*metabolism MH - Lymphocyte Count MH - Mice MH - NF-E2-Related Factor 2/*metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism MH - Oxidative Stress/drug effects MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/*drug effects MH - T-Lymphocyte Subsets/drug effects/immunology/metabolism MH - Thioredoxins/*metabolism PMC - PMC7756000 OTO - NOTNLM OT - NLRP3 OT - bixin OT - experimental autoimmune encephalomyelitis OT - nuclear factor erythroid 2-related factor 2 OT - reactive oxygen species OT - thioredoxin-interacting protein COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2020/12/29 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/01/01 CRDT- 2020/12/28 11:56 PHST- 2020/08/10 00:00 [received] PHST- 2020/11/10 00:00 [accepted] PHST- 2020/12/28 11:56 [entrez] PHST- 2020/12/29 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.593368 [doi] PST - epublish SO - Front Immunol. 2020 Dec 9;11:593368. doi: 10.3389/fimmu.2020.593368. eCollection 2020.