title: Vibsanin B preferentially targets HSP90β, inhibits interstitial leukocyte migration, and ameliorates experimental autoimmune encephalomyelitis.
abstract: Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90β. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90β and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Bai-Xin
authors: BX
authors: Ye
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
authors: Xu
authors: X
authors: Deng
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
authors: Li-Dong
authors: LD
authors: Shao
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Ying
authors: Y
authors: Lu
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Run
authors: R
authors: Xiao
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Yi-Jie
authors: YJ
authors: Liu
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Yi
authors: Y
authors: Jin
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Yin-Yin
authors: YY
authors: Xie
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Yan
authors: Y
authors: Zhao
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Liu-Fei
authors: LF
authors: Luo
authors: State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, China;
authors: Shun
authors: S
authors: Ma
authors: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; and.
authors: Ming
authors: M
authors: Gao
authors: State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen 361102, China;
authors: Lian-Ru
authors: LR
authors: Zhang
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
authors: Juan
authors: J
authors: He
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Wei-Na
authors: WN
authors: Zhang
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
authors: Yi
authors: Y
authors: Chen
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China;
authors: Cheng-Feng
authors: CF
authors: Xia
authors: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Min
authors: M
authors: Deng
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors: Ting-Xi
authors: TX
authors: Liu
authors: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; zchen@stn.sh.cn sjchen@stn.sh.cn qinshizhao@mail.kib.ac.cn.
authors: Qin-Shi
authors: QS
authors: Zhao
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; zchen@stn.sh.cn sjchen@stn.sh.cn qinshizhao@mail.kib.ac.cn.
authors: Sai-Juan
authors: SJ
authors: Chen
authors: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; zchen@stn.sh.cn sjchen@stn.sh.cn qinshizhao@mail.kib.ac.cn.
authors: Zhu
authors: Z
authors: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015027:Zebrafish
chemical_list: D004224:Diterpenes; D018841:HSP90 Heat-Shock Proteins; C000598979:vibsanin B; D051057:Proto-Oncogene Proteins c-akt