Abstract | 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: 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.
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Authors | Koffi Kouakou, Igor A Schepetkin, SangMu Jun, Liliya N Kirpotina, Ahoua Yapi, Daria S Khramova, David W Pascual, Yury S Ovodov, Mark A Jutila, Mark T Quinn |
Journal | BMC complementary and alternative medicine
(BMC Complement Altern Med)
Vol. 13
Pg. 149
(Jun 28 2013)
ISSN: 1472-6882 [Electronic] England |
PMID | 23806004
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Chemokine CCL2
- Cytokines
- Immunologic Factors
- Polysaccharides
- Toll-Like Receptor 4
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Topics |
- Animals
- Chemokine CCL2
(genetics, immunology)
- Clerodendrum
(chemistry)
- Cytokines
(genetics, immunology)
- Encephalomyelitis, Autoimmune, Experimental
(drug therapy, genetics, immunology)
- Female
- Humans
- Immunologic Factors
(administration & dosage, isolation & purification)
- Leukocytes, Mononuclear
(drug effects, immunology)
- Macrophages
(drug effects, immunology)
- Mice
- Polysaccharides
(administration & dosage, isolation & purification)
- Toll-Like Receptor 4
(genetics, immunology)
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