A RG-II Type Polysaccharide Purified from Aconitum coreanum Alleviates Lipopolysaccharide-Induced Inflammation by Inhibiting the NF-κB Signal Pathway

Abstract

Korean mondshood root polysaccharides (KMPS) isolated from the root of Aconitum coreanum (Lévl.) 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) -β-D-Galp (1→3)-β-L-Rhap-(1→4)-β-D-GalpA-(1→3)-β-D-Galp-(1→] with the side chain →5)-β-D-Arap (1→3, 5)-β-D-Arap (1→ attached to the backbone through O-4 of (1→3,4)-L-Rhap. T-β-D-Galp is attached to the backbone through O-6 of (1→3,6)-β-D-Galp residues and T-β-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 µg/mL) inhibits iNOS, TLR4, phospho-NF-κB–p65 expression, phosphor-IKK, phosphor-IκB-α expression as well as the degradation of IκB-α and the gene expression of inflammatory cytokines (TNF-α, IL-1β, iNOS and IL-6) mediated by the NF-κB signal pathways in macrophages. KMPS-2E also inhibited LPS-induced activation of NF-κB as assayed by electrophorectic mobility shift assay (EMSA) in a dose-dependent manner and it reduced NF-κB DNA binding affinity by 62.1% at 200µg/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.

Structural characteristics of pineapple pulp polysaccharides and their antitumor cell proliferation activities

“…Moreover, several peaks were observed at 175-178 ppm, which confirmed the presence of non-esterified GalA. 26 It could be seen that different levels of methyl ester were detected in PAPs 1-3, with PAP 2 showing the highest degree of methylation. These findings were consistent with the GalA level quantified by high-performance liquid chromatography.…”

“…The methyl ester at 53.8/3.80 was further evidence of methyl‐esterified GalA. Moreover, several peaks were observed at 175–178 ppm, which confirmed the presence of non‐esterified GalA . It could be seen that different levels of methyl ester were detected in PAPs 1–3, with PAP 2 showing the highest degree of methylation.…”

Non-alkaloidal constituents from the genus Aconitum: a review

“…of 67 6000 Da, and its sulfated derivatives exhibited better anticomplementary activity than heparin, which indicated its potential as a complement inhibitor. 69 70 KMPS-2E showed signicant anti-inammatory effects both in LPS-stimulated RAW 264.7 macrophages and carrageenaninduced hind paw oedema models. KMPS-2E could inhibit the expression of iNOS and inammatory cytokines mediated by the NF-kB signalling pathways in macrophages.…”

Chemical and biological studies of Aconitum pharmaceutical resources

“…A RG-II-type polysaccharide purified from A. coreanum alleviates LPS-induced inflammation by inhibiting the NF-kB signal pathway (Li et al, 2014a).…”