phenanthrenes and Demyelinating-Diseases

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.

Topics: Animals; Demyelinating Diseases; Diterpenes; Down-Regulation; Encephalomyelitis, Autoimmune, Experimental; Female; Immunosuppressive Agents; Inflammation; Janus Kinases; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-kappa B; Phenanthrenes; Signal Transduction; Spinal Cord; STAT1 Transcription Factor

Triptolide (TPT), a diterpenoid triepoxide, is the major component isolated from the Chinese herb Tripterygium wilfordii Hook. f. Previous studies have shown that TPT has immunosuppressive properties and is effective in prolonging graft survival and suppressing autoimmune responses. The aim of this study was to investigate the protective effect of TPT in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Treatment of C57BL/6 mice with TPT from the date of EAE induction significantly delayed EAE onset and suppressed disease severity, accompanied with reduced inflammation and demyelination in the central nervous system. TPT treatment lead to a significant inhibition of the mRNA expression of both Th1/Th(IL-17) and Th2 cytokines in spleen mononuclear cells (MNC) as well as in spinal cord tissues. In addition, the expression of Forkhead box p3 (Foxp3) was up-regulated in spleen MNC after TPT treatment. Furthermore, we detected apparent inhibition of nuclear factor-kappa B (NF-kappaB)-DNA binding activity, increased expression of the inhibitor of nuclear factor-kappa Balpha (IkappaBalpha) and decreased expression of pIkappaBalpha in spleen MNC in TPT-treated EAE mice. Taken together, these findings indicate that TPT has profound immunoregulatory functions and potential protective values for the treatment of autoimmune inflammatory disorders.

Topics: Animals; Blotting, Western; Cell Proliferation; Cytokines; Demyelinating Diseases; Diterpenes; Electrophoretic Mobility Shift Assay; Encephalomyelitis, Autoimmune, Experimental; Epoxy Compounds; Forkhead Transcription Factors; Gene Expression; Immunosuppressive Agents; Inflammation; Leukocytes, Mononuclear; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Phenanthrenes; Reverse Transcriptase Polymerase Chain Reaction; Spinal Cord; T-Lymphocytes