Kirenol attenuates experimental autoimmune encephalomyelitis by inhibiting differentiation of Th1 and th17 cells and inducing apoptosis of effector T cells

Scientific Reports
Juan XiaoWenbin Deng

Abstract

Experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), is characterized by CNS demyelination mediated by autoreactive T cells. Kirenol, a biologically active substance isolated from Herba Siegesbeckiae, has potent anti-inflammatory activities. Here we investigated effects of kirenol on EAE. Kirenol treatment markedly delayed onset of disease and reduced clinical scores in EAE mice. Kirenol treatment reduced expression of IFN-γ and IL-17A in the serum and proportion of Th1 and Th17 cells in draining lymph nodes. Priming of lymphocytes was reduced and apoptosis of MOG-activated CD4+ T cells was increased in kirenol treated EAE mice. Kirenol treatment of healthy animals did not affect the lymphocytes in these non-immunized mice. Further in vitro studies showed that kirenol inhibited viability of MOG-specific lymphocytes and induced apoptosis of MOG-specific CD4+ T cells in a dose- and time-dependent manner. Kirenol treatment upregulated Bax,downregulated Bcl-2,and increased activation of caspase-3 and release of cytochrome c, indicating that a mitochondrial pathway was involved in kirenol induced apoptosis. Moreover, pretreatment with either a pan-caspase inhibitor z-VAD-fmk or a more specific caspase...Continue Reading

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Citations

Jul 7, 2012·PloS One·April E PriceRichard M Locksley
Apr 2, 2014·Reumatología clinica·Elena Gonzalo-Gil, María Galindo-Izquierdo
Dec 11, 2013·Brain, Behavior, and Immunity·Marta PedreñoElena Gonzalez-Rey
Jun 11, 2016·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Yu GuoQianjin Lu
Jan 5, 2016·Cytokine & Growth Factor Reviews·Mengguo LiuMing Li
Sep 7, 2020·The Journal of Pharmacy and Pharmacology·Mehrdad Nasrollahzadeh SabetEmran Esmaeilzadeh
Aug 4, 2019·Neurochemistry International·Leila MohtashamiBehjat Javadi
May 14, 2021·Oxidative Medicine and Cellular Longevity·Peramaiyan RajendranVishnu Priya Veeraraghavan
Aug 27, 2021·Journal of Ethnopharmacology·Sabrin R M IbrahimGamal A Mohamed

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Methods Mentioned

BETA
ELISA
PMA
FACS
flow cytometry
protein assay

Software Mentioned

Cell Quest

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