PMID- 23380150 OWN - NLM STAT- MEDLINE DCOM- 20130920 LR - 20240322 IS - 1878-1705 (Electronic) IS - 1567-5769 (Print) IS - 1567-5769 (Linking) VI - 15 IP - 3 DP - 2013 Mar TI - Immunomodulatory and hemagglutinating activities of acidic polysaccharides isolated from Combretum racemosum. PG - 628-37 LID - S1567-5769(13)00031-3 [pii] LID - 10.1016/j.intimp.2013.01.015 [doi] AB - Extracts of leaves of different species of the genus Combretum have been used historically to treat a variety of medicinal problems. However, little is known about the active components conferring therapeutic properties to these extracts. In the present studies, we evaluated biochemical properties and immunomodulatory activity of polysaccharides isolated from the leaves of Combretum racemosum. Water-soluble polysaccharides from leaves of C. racemosum were extracted and fractionated by DEAE-cellulose and Diaion HP-20 to obtain a Diaion-bound fraction, designated Combretum polysaccharide-acidic bound or CP-AB, which was eluted with methanol, and an unbound fraction, designated as CP-AU. Molecular weight determination, sugar analysis, and other physical and chemical characterization of the fractions were performed. Fraction CP-AU (mol. weight 5.0 kDa) contained type II arabinogalactan and had potent immunomodulatory activity, inducing the production of interleukin (IL)-1beta, -6, -10, and tumor necrosis factor-alpha (TNF-alpha) by human peripheral blood mononuclear cells (PBMC) and MonoMac-6 monocytic cells. Likewise, intraperitoneal administration of CP-AU increased in vivo serum levels of IL-6 and monocyte chemoattractant protein-1 (MCP-1) in mice. CP-AU-induced secretion of TNF-alpha in PBMC was prevented by Toll-like receptor 4 (TLR4) antagonist LPS-RS. Treatment with CP-AU induced phosphorylation of Akt2, Akt3, GSK-3beta, HSP27, mTOR, and all p38 MAPK isoforms (alpha, beta, delta, and gamma), as well as stimulation of AP-1/NF-kappaB transcriptional activity. In addition, CP-AU effectively agglutinated erythrocytes from several species, including human, mouse, and rabbit. In contrast, fraction CP-AB was inactive in all biological tests, including cytokine production and hemagglutination. These data suggest that at least part of the beneficial therapeutic effects reported for the water extracts of leaves from C. racemosum are due to modulation of leukocyte functions. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Schepetkin, Igor A AU - Schepetkin IA AD - Department of Immunology and Infectious Diseases, Montana State University, Bozeman, MT 59717, USA. FAU - Kouakou, Koffi AU - Kouakou K FAU - Yapi, Ahoua AU - Yapi A FAU - Kirpotina, Liliya N AU - Kirpotina LN FAU - Jutila, Mark A AU - Jutila MA FAU - Quinn, Mark T AU - Quinn MT LA - eng GR - P30 GM110732/GM/NIGMS NIH HHS/United States GR - P01 AT004986/AT/NCCIH NIH HHS/United States GR - P20 GM103500/GM/NIGMS NIH HHS/United States 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 DEP - 20130201 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Cytokines) RN - 0 (Galactans) RN - 0 (Plant Extracts) RN - 0 (Polysaccharides) RN - 0 (Toll-Like Receptor 4) RN - SL4SX1O487 (arabinogalactan) SB - IM MH - Agglutination/drug effects MH - Animals MH - Cell Line MH - Combretum/*chemistry MH - Cytokines/metabolism MH - Erythrocytes/drug effects MH - Galactans/*administration & dosage/chemistry/isolation & purification MH - Humans MH - Leukocytes, Mononuclear/*drug effects/immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Monocytes/*drug effects/immunology MH - Plant Extracts/*administration & dosage/chemistry MH - Plant Leaves/chemistry MH - Polysaccharides/*administration & dosage/chemistry/isolation & purification MH - Signal Transduction/drug effects MH - Toll-Like Receptor 4/antagonists & inhibitors PMC - PMC3647372 MID - NIHMS458502 EDAT- 2013/02/06 06:00 MHDA- 2013/09/21 06:00 PMCR- 2014/03/01 CRDT- 2013/02/06 06:00 PHST- 2012/11/12 00:00 [received] PHST- 2013/01/09 00:00 [revised] PHST- 2013/01/17 00:00 [accepted] PHST- 2013/02/06 06:00 [entrez] PHST- 2013/02/06 06:00 [pubmed] PHST- 2013/09/21 06:00 [medline] PHST- 2014/03/01 00:00 [pmc-release] AID - S1567-5769(13)00031-3 [pii] AID - 10.1016/j.intimp.2013.01.015 [doi] PST - ppublish SO - Int Immunopharmacol. 2013 Mar;15(3):628-37. doi: 10.1016/j.intimp.2013.01.015. Epub 2013 Feb 1.