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However, little is known about the high-molecular weight active components conferring therapeutic properties to these extracts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Polysaccharides from the leaves of<jats:italic>Clerodendrum splendens<\/jats:italic>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 (<jats:italic>i.p.<\/jats:italic>) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fractions containing type II arabinogalactan had potent immunomodulatory activity. Specifically, the high-molecular weight sub-fraction<jats:bold>CSP-AU1<\/jats:bold>(average of 38.5 kDa) induced NO and cytokine [interleukin (IL)-1\u03b1, -1\u03b2, -6, -10, tumor necrosis factor (TNF; designated previously as TNF-\u03b1), and granulocyte macrophage-colony stimulating factor (GM-CSF)] production by human peripheral blood mononuclear cells (PBMCs) and monocyte\/macrophages.<jats:bold>CSP-AU1-<\/jats:bold>induced secretion of TNF was prevented by Toll-like receptor 4 (TLR4) antagonist LPS-RS, indicating a role for TLR4 signaling. Treatment with<jats:bold>CSP-AU1<\/jats:bold>also induced phosphorylation of a number of MAPKs in human PBMC and activated AP-1\/NF-\u03baB.<jats:italic>In vivo<\/jats:italic>treatment of mice with<jats:bold>CSP-AU1<\/jats:bold>and<jats:bold>CSP-NU1<\/jats:bold>resulted in increased serum IL-6, IL-10, TNF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1\u03b1\/CCL3, and MIP-1\u03b2\/CCL4.<jats:bold>CSP-AU1<\/jats:bold>treatment of mice with EAE (50 mg\/kg,<jats:italic>i.p.<\/jats:italic>, daily, 13 days) resulted in significantly reduced disease severity in this experimental model of multiple sclerosis. Levels of IL-13, TNF, interferon (IFN)-\u03b3, IL-17, and GM-CSF were also significantly decreased, whereas transforming growth factor (TGF)-\u03b2 was increased in LN cells from<jats:bold>CSP-AU1<\/jats:bold>-treated EAE mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Polysaccharide<jats:bold>CSP-AU1<\/jats:bold>is a potent natural innate immunomodulator with a broad spectrum of agonist activity<jats:italic>in vitro<\/jats:italic>and immunosupressive properties after chronic administration<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1472-6882-13-149","type":"journal-article","created":{"date-parts":[[2013,6,28]],"date-time":"2013-06-28T08:14:08Z","timestamp":1372407248000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Immunomodulatory activity of polysaccharides isolated from Clerodendrum splendens: Beneficial effects in experimental autoimmune encephalomyelitis"],"prefix":"10.1186","volume":"13","author":[{"given":"Koffi","family":"Kouakou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor A","family":"Schepetkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SangMu","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliya N","family":"Kirpotina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahoua","family":"Yapi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria S","family":"Khramova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Pascual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury S","family":"Ovodov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Jutila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,6,28]]},"reference":[{"key":"1417_CR1","doi-asserted-by":"publisher","first-page":"986797","DOI":"10.1155\/2011\/986797","volume":"2011","author":"SH Venkatesha","year":"2011","unstructured":"Venkatesha SH, Rajaiah R, Berman BM, Moudgil KD: Immunomodulation of Autoimmune Arthritis by Herbal CAM. 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