Parthenolide Modulates Immune Response in Cells from C57BL/6 Mice Induced with Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis is a chronic inflammatory and autoimmune disease of the central nervous system that affects more than 2.5 million people worldwide. Experimental autoimmune encephalomyelitis is a murine autoimmune disease used to study multiple sclerosis. Parthenolide, a natural sesquiterpene lactone found in Tanacetum parthenium L., is known for its strong anti-inflammatory activity. Herein, we have investigated the in vitro immunomodulatory effects of parthenolide on cytokine production and nitric oxide in cultured cells from myelin oligodendrocyte glycoprotein 35-55 amino acid peptide mice. Experimental autoimmune encephalomyelitis was induced in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide, and parthenolide was isolated from T. parthenium. Splenocytes and peritoneal cells were obtained from experimental autoimmune encephalomyelitis-induced mice and incubated with parthenolide (1, 5, and 20 µM). After in vitro treatment with parthenolide, supernatants were collected, and nitric oxide and cytokines were measured. The results suggested that parthenolide may regulate the activity of Th17 and Th1 cells, mainly by decreasing IL-17, TNF-α, and interferon gamma production. This modulation may be related to the lower levels of IL-12p40 and IL-6 after treatment with parthenolide. It was shown, for the first time, that parthenolide presents in vitro immunomodulatory effects on inflammatory mediators produced by cells from experimental autoimmune encephalomyelitis-induced mice.

Immunomodulatory effects of licochalcone A on experimental autoimmune encephalomyelitis.

OBJECTIVES: Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. Herein, we have investigated the immunomodulatory effect of licochalcone A (LicoA) on NO, H2 O2 , tumour necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ) and IL-17 production in cultured cells from EAE mice. METHODS: EAE was induced in C57Bl/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55 ). LicoA was isolated from the roots of Glycyrrhiza inflata. Splenocytes were obtained from EAE mice and incubated with LicoA (4, 20 and 40 µm). Peritoneal cells were obtained from EAE mice treated with LicoA (15 and 30 mg/kg/day. p.o.). H2 O2 , NO, IFN-γ, TNF-α and IL-17 production was determined in the presence or absence of concanavalin (ConA) or MOG35-55 stimulation. KEY FINDINGS: LicoA (40 µm) inhibited H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in splenocytes spontaneously or after both ConA and MOG35-55 stimulation. LicoA (30 mg/kg/day) reduced clinical score and severity of EAE mice, and inhibited TNF-α, IFN-γ and IL-17 production in peritoneal cells. CONCLUSIONS: LicoA possesses immunomodulatory effects on H2 O2 , NO, IFN-γ, TNF-α and IL-17 production in cells from EAE mice. It is suggested that LicoA acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.