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

BMC Complementary and Alternative Medicine

Mark T Quinn⁵  Mark A Jutila⁵  Yury S Ovodov¹  David W Pascual²  Daria S Khramova¹  Ahoua Yapi³  Liliya N Kirpotina⁵  SangMu Jun²  Igor A Schepetkin⁵  Koffi Kouakou⁴ 

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

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

Others  :  1229431
DOI  :  10.1186/1472-6882-13-149

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

【 摘 要 】

Background

Extracts 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.

Methods

Polysaccharides 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.

Results

Fractions 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.

Conclusions

Polysaccharide 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】

   
2013 Kouakou et al.; licensee BioMed Central Ltd.

【 图 表 】

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