PMID- 24927178 OWN - NLM STAT- MEDLINE DCOM- 20150511 LR - 20231110 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 6 DP - 2014 TI - A RG-II type polysaccharide purified from Aconitum coreanum alleviates lipopolysaccharide-induced inflammation by inhibiting the NF-kappaB signal pathway. PG - e99697 LID - 10.1371/journal.pone.0099697 [doi] LID - e99697 AB - Korean mondshood root polysaccharides (KMPS) isolated from the root of Aconitum coreanum (Levl.) Rapaics have shown anti-inflammatory activity, which is strongly influenced by their chemical structures and chain conformations. However, the mechanisms of the anti-inflammatory effect by these polysaccharides have yet to be elucidated. A RG-II polysaccharide (KMPS-2E, Mw 84.8 kDa) was isolated from KMPS and its chemical structure was characterized by FT-IR and NMR spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography. The backbone of KMPS-2E consisted of units of [-->6) -beta-D-Galp (1-->3)-beta-L-Rhap-(1-->4)-beta-D-GalpA-(1-->3)-beta-D-Galp-(1-->] with the side chain -->5)-beta-D-Arap (1-->3, 5)-beta-D-Arap (1--> attached to the backbone through O-4 of (1-->3,4)-L-Rhap. T-beta-D-Galp is attached to the backbone through O-6 of (1-->3,6)-beta-D-Galp residues and T-beta-D-Ara is connected to the end group of each chain. The anti-inflammatory effects of KMPS-2E and the underlying mechanisms using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and carrageenan-induced hind paw edema were investigated. KMPS-2E (50, 100 and 200 microg/mL) inhibits iNOS, TLR4, phospho-NF-kappaB-p65 expression, phosphor-IKK, phosphor-IkappaB-alpha expression as well as the degradation of IkappaB-alpha and the gene expression of inflammatory cytokines (TNF-alpha, IL-1beta, iNOS and IL-6) mediated by the NF-kappaB signal pathways in macrophages. KMPS-2E also inhibited LPS-induced activation of NF-kappaB as assayed by electrophorectic mobility shift assay (EMSA) in a dose-dependent manner and it reduced NF-kappaB DNA binding affinity by 62.1% at 200 microg/mL. In rats, KMPS-2E (200 mg/kg) can significantly inhibit carrageenan-induced paw edema as ibuprofen (200 mg/kg) within 3 h after a single oral dose. The results indicate that KMPS-2E is a promising herb-derived drug against acute inflammation. FAU - Li, Xiaojun AU - Li X AD - Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China; The MOE Key Laboratory for Standardization of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Jiang, Jiaye AU - Jiang J AD - Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Shi, Songshan AU - Shi S AD - The MOE Key Laboratory for Standardization of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Shanghai R&D Center for Standardization of Chinese Medicines, Shanghai, China. FAU - Bligh, S W Annie AU - Bligh SW AD - Department of Complementary Medicine, Faculty of Science and Technology, University of Westminster, Westminster, United Kingdom. FAU - Li, Yuan AU - Li Y AD - Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Jiang, Yongbo AU - Jiang Y AD - Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Huang, Dan AU - Huang D AD - Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Ke, Yan AU - Ke Y AD - Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Wang, Shunchun AU - Wang S AD - The MOE Key Laboratory for Standardization of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Shanghai R&D Center for Standardization of Chinese Medicines, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140613 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Polysaccharides) SB - IM MH - Aconitum/*chemistry MH - Animals MH - Blotting, Western MH - Cell Line MH - Electrophoretic Mobility Shift Assay MH - Inflammation/*chemically induced/*drug therapy MH - Lipopolysaccharides/*pharmacology MH - Magnetic Resonance Spectroscopy MH - Male MH - Mice MH - NF-kappa B/*metabolism MH - Plant Extracts/chemistry/*therapeutic use MH - Polysaccharides/chemistry/*therapeutic use MH - Rats MH - Rats, Wistar MH - Signal Transduction/drug effects PMC - PMC4057409 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/06/14 06:00 MHDA- 2015/05/12 06:00 PMCR- 2014/06/13 CRDT- 2014/06/14 06:00 PHST- 2014/01/20 00:00 [received] PHST- 2014/05/17 00:00 [accepted] PHST- 2014/06/14 06:00 [entrez] PHST- 2014/06/14 06:00 [pubmed] PHST- 2015/05/12 06:00 [medline] PHST- 2014/06/13 00:00 [pmc-release] AID - PONE-D-14-02845 [pii] AID - 10.1371/journal.pone.0099697 [doi] PST - epublish SO - PLoS One. 2014 Jun 13;9(6):e99697. doi: 10.1371/journal.pone.0099697. eCollection 2014.