PMID- 23806004
OWN - NLM
STAT- MEDLINE
DCOM- 20130923
LR  - 20211021
IS  - 1472-6882 (Electronic)
IS  - 1472-6882 (Linking)
VI  - 13
DP  - 2013 Jun 28
TI  - Immunomodulatory activity of polysaccharides isolated from Clerodendrum 
      splendens: beneficial effects in experimental autoimmune encephalomyelitis.
PG  - 149
LID - 10.1186/1472-6882-13-149 [doi]
AB  - 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)-1alpha, -1beta, -6, -10, tumor necrosis factor (TNF; 
      designated previously as TNF-alpha), 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-kappaB. 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)-1alpha/CCL3, 
      and MIP-1beta/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)-gamma, IL-17, and 
      GM-CSF were also significantly decreased, whereas transforming growth factor 
      (TGF)-beta 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.
FAU - Kouakou, Koffi
AU  - Kouakou K
AD  - Department of Immunology and Infectious Diseases, Montana State University, 
      Bozeman, MT 59717, USA.
FAU - Schepetkin, Igor A
AU  - Schepetkin IA
FAU - Jun, SangMu
AU  - Jun S
FAU - Kirpotina, Liliya N
AU  - Kirpotina LN
FAU - Yapi, Ahoua
AU  - Yapi A
FAU - Khramova, Daria S
AU  - Khramova DS
FAU - Pascual, David W
AU  - Pascual DW
FAU - Ovodov, Yury S
AU  - Ovodov YS
FAU - Jutila, Mark A
AU  - Jutila MA
FAU - Quinn, Mark T
AU  - Quinn MT
LA  - eng
GR  - AT04986/AT/NCCIH NIH HHS/United States
GR  - GM103500/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130628
PL  - England
TA  - BMC Complement Altern Med
JT  - BMC complementary and alternative medicine
JID - 101088661
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Immunologic Factors)
RN  - 0 (Polysaccharides)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics/immunology
MH  - Clerodendrum/*chemistry
MH  - Cytokines/genetics/immunology
MH  - Encephalomyelitis, Autoimmune, Experimental/*drug therapy/genetics/immunology
MH  - Female
MH  - Humans
MH  - Immunologic Factors/*administration & dosage/isolation & purification
MH  - Leukocytes, Mononuclear/drug effects/immunology
MH  - Macrophages/drug effects/immunology
MH  - Mice
MH  - Polysaccharides/*administration & dosage/isolation & purification
MH  - Toll-Like Receptor 4/genetics/immunology
PMC - PMC3717075
EDAT- 2013/06/29 06:00
MHDA- 2013/09/24 06:00
PMCR- 2013/06/28
CRDT- 2013/06/29 06:00
PHST- 2013/02/22 00:00 [received]
PHST- 2013/06/20 00:00 [accepted]
PHST- 2013/06/29 06:00 [entrez]
PHST- 2013/06/29 06:00 [pubmed]
PHST- 2013/09/24 06:00 [medline]
PHST- 2013/06/28 00:00 [pmc-release]
AID - 1472-6882-13-149 [pii]
AID - 10.1186/1472-6882-13-149 [doi]
PST - epublish
SO  - BMC Complement Altern Med. 2013 Jun 28;13:149. doi: 10.1186/1472-6882-13-149.