Involvement of JAK/STAT signaling in the effect of cornel iridoid glycoside on experimental autoimmune encephalomyelitis amelioration in rats

Linlin Yin; Yongyan Chen; Zhao Qu; Li Zhang; Qi Wang; Qi Zhang; Lin Li

doi:10.1016/j.jneuroim.2014.06.022

Involvement of JAK/STAT signaling in the effect of cornel iridoid glycoside on experimental autoimmune encephalomyelitis amelioration in rats

J Neuroimmunol. 2014 Sep 15;274(1-2):28-37. doi: 10.1016/j.jneuroim.2014.06.022. Epub 2014 Jun 28.

Authors

Linlin Yin¹, Yongyan Chen², Zhao Qu³, Li Zhang⁴, Qi Wang³, Qi Zhang², Lin Li⁵

Affiliations

¹ Department of Pharmacology, Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China. Electronic address: yinll913@126.com.
² School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan Province 450001, PR China.
³ Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Guangzhou, Guangdong Province 510405, PR China.
⁴ Department of Pharmacology, Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China.
⁵ Department of Pharmacology, Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 45 Changchun Street, Beijing 100053, PR China. Electronic address: linli97@hotmail.com.

PMID: 25012120
DOI: 10.1016/j.jneuroim.2014.06.022

Abstract

In the present study, we investigated the therapeutic benefit of cornel iridoid glycoside (CIG), the main component extracted from Cornus officinalis, in experimental autoimmune encephalomyelitis (EAE) rats. CIG was intragastrically administered daily after EAE initiation for 20days and reduced disease severity, incidence, disease onset and ongoing paralysis. Histopathological staining showed that CIG could reduce T cell entry to the central nervous system and microglia activation, increased brain-derived neurotrophic factor (BDNF) expression and mature oligodendrocytes, and decreased oligodendrocyte progenitor cells (OPCs). Also, CIG treatment inhibited brain JAK/STAT1/3 and reduced proinflammatory cytokines. CIG might be a novel potential therapeutic agent for multiple sclerosis (MS).

Keywords: Cornel iridoid glycoside; Experimental autoimmune encephalomyelitis; JAK/STAT signaling; Multiple sclerosis; Neuroinflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain-Derived Neurotrophic Factor / immunology
Brain-Derived Neurotrophic Factor / metabolism
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / metabolism
Female
Iridoid Glucosides / pharmacology*
Janus Kinase 1 / metabolism
Janus Kinase 3 / metabolism
Multiple Sclerosis / drug therapy
Multiple Sclerosis / immunology
Multiple Sclerosis / metabolism
Myelin Sheath / drug effects
Myelin Sheath / immunology
NF-kappa B / immunology
NF-kappa B / metabolism
Oligodendroglia / drug effects
Oligodendroglia / immunology
Oligodendroglia / metabolism
Rats
Rats, Inbred Lew
STAT1 Transcription Factor / metabolism
STAT3 Transcription Factor / metabolism
Signal Transduction / drug effects*
Signal Transduction / immunology*
Spinal Cord / drug effects
Spinal Cord / immunology
Spinal Cord / metabolism
Treatment Outcome

Substances

Brain-Derived Neurotrophic Factor
Iridoid Glucosides
Jak3 protein, rat
NF-kappa B
STAT1 Transcription Factor
STAT3 Transcription Factor
Stat1 protein, rat
Stat3 protein, rat
Jak1 protein, rat
Janus Kinase 1
Janus Kinase 3