Immunomodulatory activity of polysaccharides isolated from Clerodendrum splendens: Beneficial effects in experimental autoimmune encephalomyelitis

BMC Complementary and Alternative Medicine

Research Article

Mark A Jutila¹  Igor A Schepetkin¹  Mark T Quinn¹  Liliya N Kirpotina¹  Koffi Kouakou²  David W Pascual³  SangMu Jun³  Ahoua Yapi⁴  Yury S Ovodov⁵  Daria S Khramova⁵ 

[1] Department of Immunology and Infectious Diseases, Montana State University, 59717, Bozeman, MT, USA;Department of Immunology and Infectious Diseases, Montana State University, 59717, Bozeman, MT, USA;Laboratoire d’Endocrinologie et Biologie de la Reproduction, Université de Cocody-Abidjan, Abidjan, Côte d’Ivoire;Department of Infectious Diseases and Pathology, University of Florida, 32611, Gainesville, FL, USA;Institut National de la Santé Public, Abidjan, Côte d’Ivoire;Institute of Physiology, Komi Science Centre, The Urals Branch of the Russian Academy of Sciences, Syktyvkar, Russia;

关键词: Clerodendrum splendens;    Polysaccharide;    Macrophage;    Cytokine;    Immunomodulation;   

DOI  :  10.1186/1472-6882-13-149

 received in 2013-02-22, accepted in 2013-06-20,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundExtracts of leaves from Clerodendrum have been used for centuries to treat a variety of medicinal problems in tropical Africa. However, little is known about the high-molecular weight active components conferring therapeutic properties to these extracts.MethodsPolysaccharides from the leaves of Clerodendrum splendens were extracted and fractionated by ion exchange and size-exclusion chromatography. Molecular weight determination, sugar analysis, degree of methyl esterification, and other chemical characterization of the fractions were performed. Immunomodulatory activity of the fractions was evaluated by determining their ability to induce monocyte/macrophage nitric oxide (NO), cytokine production, and mitogen-activated protein kinase (MAPK) phosphorylation. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice, and severity of EAE was monitored in mice treated with intraperitoneal (i.p.) injections of the most active polysaccharide fraction. Lymph nodes (LN) and spleen were harvested, and levels of cytokines in supernatants from LN cells and splenocytes challenged with myelin oligodendrocyte glycoprotein peptide were determined.ResultsFractions containing type II arabinogalactan had potent immunomodulatory activity. Specifically, the high-molecular weight sub-fraction CSP-AU1 (average of 38.5 kDa) induced NO and cytokine [interleukin (IL)-1α, -1β, -6, -10, tumor necrosis factor (TNF; designated previously as TNF-α), and granulocyte macrophage-colony stimulating factor (GM-CSF)] production by human peripheral blood mononuclear cells (PBMCs) and monocyte/macrophages. CSP-AU1- induced secretion of TNF was prevented by Toll-like receptor 4 (TLR4) antagonist LPS-RS, indicating a role for TLR4 signaling. Treatment with CSP-AU1 also induced phosphorylation of a number of MAPKs in human PBMC and activated AP-1/NF-κB. In vivo treatment of mice with CSP-AU1 and CSP-NU1 resulted in increased serum IL-6, IL-10, TNF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α/CCL3, and MIP-1β/CCL4. CSP-AU1 treatment of mice with EAE (50 mg/kg, i.p., daily, 13 days) resulted in significantly reduced disease severity in this experimental model of multiple sclerosis. Levels of IL-13, TNF, interferon (IFN)-γ, IL-17, and GM-CSF were also significantly decreased, whereas transforming growth factor (TGF)-β was increased in LN cells from CSP-AU1-treated EAE mice.ConclusionsPolysaccharide CSP-AU1 is a potent natural innate immunomodulator with a broad spectrum of agonist activity in vitro and immunosupressive properties after chronic administration in vivo.

【 授权许可】

Unknown   
© Kouakou et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.