Mangiferin Promotes Bregs Level,Activates Nrf2 Antioxidant Signaling,and Inhibits Proinflammatory Cytokine Expression in Murine Splenic Mononuclear Cells In Vitro  

作　　者：Zhi-zhi QIN Jun RUAN Meng-ran LEE Kang SUN Ping CHEN Yan CHEN Mei HONG Ling-hui XIA Jun FANG Hao TANG 

机构地区：[1]Department of Hematology,Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China [2]Department of Hematology,Huaihe Hospital of Henan University,Kaifeng 475000,China [3]Department of Gastroenterology,Wuhan Resources&Wisco General Hospital,Wuhan 430080,China [4]Collaborative Innovation Center of Hematology,Soochow University,Suzhou 215000,China [5]Department of Cardiovascular Surgery,Zhongnan Hospital,Wuhan University,Wuhan 430071,China

出　　处：《Current Medical Science》2021年第3期454-464,共11页当代医学科学（英文）

基　　金：the National Natural Science Foundation of China(No.81470347,No.81974003);The authors would like to thank the Department of Central Laboratory,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China,for providing relevant experimental facilities and technical support.

摘　　要：Recent studies indicated that regulatory B cells(Bregs)and nuclear factor erythroid 2-related factor 2(Nrf2)antioxidant signaling pathway play important roles in the pathogenesis of chronic graft-versus-host disease(cGVHD).Mangiferin(MA),a polyphenol compound,has been reported to activate Nrf2/antioxidant-responsive element(ARE)signaling pathway.This study was aimed to investigate the effects of MA on Bregs and Nrf2 antioxidant signaling in murine splenic mononuclear cells(MNCs)in vitro.Our results revealed that MA could increase the Bregs level in murine splenic MNCs.Moreover,MA up-regulated the expression of Bregs-associated immunosuppressive factor interleukin-10(IL-10)by activating the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)and extracellular signal-regulated kinase(ERK)signaling in murine splenic MNCs.Meanwhile,MA inhibited the proinflammatory cytokines IL-2 and interferon-y(INF-y)at both mRNA and protein levels.MA also enhanced the transcription and protein expression of Nrf2 and NADPH quinine oxidoreductase 1(NQOl),whereas decreased that of Kelch-like ECH-associated protein 1(Keapl)in murine splenic MNCs.Moreover,MA promoted the proliferation and inhibited the apoptosis of murine splenic MNCs.These results suggested that MA exerts immunosuppressive effects by upregulating the Bregs level,activating the Nrf2 antioxidant pathway,and inhibiting the expression of pro-immunoinflammatory factors.MA,as a natural immunomodulatory and anti-inflammatory agent,may have a potential role in the prophylaxis and treatment of cGVHD.

关 键 词：MANGIFERIN regulatory B cells nuclear factor erythroid 2-related factor 2 INTERLEUKIN-10 IMMUNOMODULATION anti-inflammation 

分 类 号：R73[医药卫生—肿瘤]