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: Jian Zhang, Yu-qi Zeng, Jing Zhang, Xiao-dong Pan, De-yong Kang, Tian-wen Huang, Xiao-chun Chen
• Journal: Journal of neurochemistry (J Neurochem) Vol. 133 Issue 1 Pg. 104-12 (Apr 2015) ISSN: 1471-4159 [Electronic] England
• PMID: 25662403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 International Society for Neurochemistry.

Chemical References

• Diterpenes
• Immunosuppressive Agents
• NF-kappa B
• Phenanthrenes
• STAT1 Transcription Factor
• Stat1 protein, mouse
• tripchlorolide
• Janus Kinases

Topics

• Animals
• Demyelinating Diseases (pathology)
• Diterpenes (therapeutic use)
• Down-Regulation (drug effects)
• Encephalomyelitis, Autoimmune, Experimental (drug therapy, pathology)
• Female
• Immunosuppressive Agents (therapeutic use)
• Inflammation (pathology)
• Janus Kinases (drug effects)
• MAP Kinase Signaling System (drug effects)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (drug effects)
• Phenanthrenes (therapeutic use)
• STAT1 Transcription Factor (drug effects)
• Signal Transduction (drug effects)
• Spinal Cord (pathology)