Tripchlorolide ameliorates experimental autoimmune encephalomyelitis by down‐regulating ERK1/2‐NF‐κB and JAK/STAT signaling pathways

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. Tripchlorolide (T4), a traditional Chinese herbal compound, has been found to possess anti‐inflammatory and immunosuppressive functions, but the underlying mechanism is not clear. In this study, we demonstrated for the first time that T4 can ameliorate inflammatory infiltrates and demyelination in EAE‐inflicted animals. T4 may work by down‐regulating ERK1/2‐NF‐κВ and JAK/STAT signaling pathways, and altering the expression of cytokines. Our findings suggest that T4 may be a promising novel therapeutic option for the treatment of MS. MOG35‐55, myelin oligodendrocyte glycoprotein peptide; T4, tripchlorolide; NF‐κB, nuclear factor kappa B; ERK1/2, extracelluar regulated kinase1/2; JNK, Jun N‐terminal kinases; JAK, Janus protein‐tyrosine kinases; STAT, signal transducer and activator of transcription; IL‐4, interleukin‐4; IL‐5, interleukin‐5; IL‐17, interleukin‐17; IFN‐γ, and interferon‐γ. Tripchlorolide (T4), a traditional Chinese herbal compound, has been found to possess anti‐inflammatory and immunosuppressive functions, but the underlying mechanism is not clear. In this study, we demonstrated for the first time that T4 can ameliorate inflammatory infiltrates and demyelination in EAE‐inflicted animals. T4 may work by down‐regulating ERK1/2‐NF‐κВ and JAK/STAT signaling pathways, and altering the expression of cytokines. Our findings suggest that T4 may be a promising novel therapeutic option for the treatment of MS. MOG35‐55, myelin oligo