Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Mingyue Li;Weina Guo;Yalan Dong;Wenzhu Wang;Chunxia Tian;Zili Zhang;Ting Yu;Haifeng Zhou;Yang Gui;Kaming Xue;Junyi Li;Feng Jiang;Alexey Sarapultsev;Huafang Wang;Ge Zhang;Shanshan Luo;Heng Fan;Desheng Hu

Department of Integrated Traditional Chinese and Western Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Department of Gastroenterology,Zhongda Hospital,Southeast University,Nanjing 210009,China;Institute of International Education,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Institute of Immunology and Physiology,Ural Branch of the Russian Academy of Sciences,Ekaterinburg 620049,Russia;Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China;Institute of Integrated Bioinfomedicine and Translational Science,School of Chinese Medicine,Hong Kong Baptist University,Hong Kong Special Administrative Region 999077,China

基因组蛋白质组与生物信息学报（英文版）

[1]Mingyue Li;Weina Guo;Yalan Dong;Wenzhu Wang;Chunxia Tian;Zili Zhang;Ting Yu;Haifeng Zhou;Yang Gui;Kaming Xue;Junyi Li;Feng Jiang;Alexey Sarapultsev;Huafang Wang;Ge Zhang;Shanshan Luo;Heng Fan;Desheng Hu-.Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice)[J].基因组蛋白质组与生物信息学报（英文版）,2022(02):288-303

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Beneficial,Effects,Celastrol,Immune,Balance,by,Modulating,Gut,Microbiota,Experimental,Ulcerative,Colitis,Mice,colitis,UC,chronic,inflammatory,bowel,disease,caused,many,factors,including,colonic,inflammation,microbiota,dysbiosis,Previous,studies,have,indicated,that,celastrol,CSR,has,strong,anti,immune,inhibitory,effects,Here,investigated,mucosal,immunity,experimental,model,addressed,mechanism,which,exerts,protective,We,characterized,potential,treating,using,histological,staining,intestinal,permeability,assay,flow,cytometry,fecal,transplantation,FMT,16S,rRNA,sequencing,untargeted,metabolomics,cell,differentiation,significantly,ameliorated,dextran,sodium,sulfate,DSS,induced,mice,was,evidenced,recovered,body,weight,length,well,decreased,activity,DAI,score,Meanwhile,down,regulated,production,cytokines,up,amount,mediators,both,protein,levels,improved,balances,Treg,Thl,Th1,maintain,homeostasis,Notably,all,therapeutic,were,exerted,gut,dependent,manner,Furthermore,treatment,increased,diversity,changed,compositions,metabolites,probably,associated,mediated,In,conclusion,this,study,provides,may,be,promising,drug

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