title: Tripchlorolide ameliorates experimental autoimmune encephalomyelitis by down-regulating ERK1/2-NF-κB and JAK/STAT signaling pathways.
abstract: Tripchlorolide (T4), an extract of the natural herb Tripterygium wilfordii Hook F, has been found to possess anti-inflammatory and immunosuppressive actions. In the current study, these actions were evaluated in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis by scoring the clinical signs, observing the infiltration of inflammatory cells and myelin sheath in the lumbar spinal cord of EAE mice. The results demonstrated that T4 (at a dose of 40 μg/kg) significantly reduced the severity of EAE and slowed down the ongoing EAE. Further analysis showed that T4 suppressed the mRNA and protein levels of the transcription factors T-bet and RoRrt and mRNA levels of IFN-γ and IL-17 in the spinal cords. Furthermore, T4 down-regulated the ERK1/2-NF-κB and JAK/STAT signaling pathways. At 40 μg/kg, T4 did not induce side effects on hematological parameters. These findings suggest that T4 ameliorates EAE by immunosuppression, providing a new insight into T4 application in multiple sclerosis treatment.
authors: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University Union Hospital, Fuzhou, China.
authors: Jian
authors: J
authors: Zhang
authors: Yu-qi
authors: YQ
authors: Zeng
authors: Jing
authors: J
authors: Zhang
authors: Xiao-dong
authors: XD
authors: Pan
authors: De-yong
authors: DY
authors: Kang
authors: Tian-wen
authors: TW
authors: Huang
authors: Xiao-chun
authors: XC
authors: Chen
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000473:pathology; D004224:Diterpenes / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D053612:Janus Kinases / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects*; D010616:Phenanthrenes / Q000627:therapeutic use*; D050794:STAT1 Transcription Factor / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013116:Spinal Cord / Q000473:pathology
chemical_list: D004224:Diterpenes; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D010616:Phenanthrenes; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C068051:tripchlorolide; D053612:Janus Kinases
keywords: JAK/STAT pathway; NF-κB pathway; cytokine; experimental autoimmune encepha-lomyelitis; transcription factor; tripchlorolide