Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway

Yuan Zhang; Xing Li; Bogoljub Ciric; Cun-Gen Ma; Bruno Gran; Abdolmohamad Rostami; Guang-Xian Zhang

doi:10.1038/srep17407

Therapeutic effect of baicalin on experimental autoimmune encephalomyelitis is mediated by SOCS3 regulatory pathway

Sci Rep. 2015 Nov 30:5:17407. doi: 10.1038/srep17407.

Authors

Yuan Zhang^{1

2}, Xing Li^{1

2}, Bogoljub Ciric¹, Cun-Gen Ma³, Bruno Gran⁴, Abdolmohamad Rostami¹, Guang-Xian Zhang¹

Affiliations

¹ Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
² Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, Northwest China National Engineering Laboratory for Resource Development of Endangered Crude Drugs, College of Life Sciences, Shaanxi Normal University, Xi'an, China.
³ Institute of Brain Science, Department of Neurology, Shanxi Datong University Medical School, Datong, China.
⁴ Clinical Neurology Research Group, Division of Clinical Neuroscience, University of Nottingham School of Medicine, UK.

Abstract

Natural compounds derived from medicinal plants have long been considered a rich source of novel therapeutic agents. Baicalin (Ba) is a bioactive flavonoid compound derived from the root of Scutellaria baicalensis, an herb widely used in traditional medicine for the treatment of various inflammatory diseases. In this study, we investigate the effects and mechanism of action of Ba in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Ba treatment effectively ameliorated clinical disease severity in myelin oligodendrocyte glycoprotein (MOG)35-55 peptide-induced EAE, and reduced inflammation and demyelination of the central nervous system (CNS). Ba reduced infiltration of immune cells into the CNS, inhibited expression of proinflammatory molecules and chemokines, and prevented Th1 and Th17 cell differentiation via STAT/NFκB signaling pathways. Further, we showed that SOCS3 induction is essential to the effects of Ba, given that the inhibitory effect of Ba on pathogenic Th17 responses was largely abolished when SOCS3 signaling was knocked down. Taken together, our findings demonstrate that Ba has significant potential as a novel anti-inflammatory agent for therapy of autoimmune diseases such as MS.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Cell Differentiation / drug effects
Cell Differentiation / genetics
Cytokines / metabolism
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / drug therapy
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / metabolism*
Encephalomyelitis, Autoimmune, Experimental / pathology
Female
Flavonoids / pharmacology*
Inflammation Mediators / metabolism
Lymphocyte Activation / drug effects
Lymphocyte Activation / genetics
Lymphocyte Activation / immunology
Mice
Multiple Sclerosis / drug therapy
Multiple Sclerosis / immunology
Multiple Sclerosis / metabolism
Multiple Sclerosis / pathology
NF-kappa B / metabolism
STAT Transcription Factors / metabolism
Signal Transduction / drug effects*
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins / metabolism*
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
Th1 Cells / cytology
Th1 Cells / drug effects
Th1 Cells / immunology
Th1 Cells / metabolism
Th17 Cells / cytology
Th17 Cells / drug effects
Th17 Cells / immunology
Th17 Cells / metabolism

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cytokines
Flavonoids
Inflammation Mediators
NF-kappa B
STAT Transcription Factors
Socs3 protein, mouse
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins
baicalin

Grants and funding

R01 NS075260/NS/NINDS NIH HHS/United States