title: Kalopanaxsaponin B inhibits LPS-induced inflammation by inhibiting IRAK1 Kinase.
abstract: The stem bark of Kalopanax pictus Nakai (KP, family Araliaceae), of which main constituent is kalopanaxsaponin B, has been used for inflammation in Chinese traditional medicine. We isolated kalopanaxsaponin B from KP and investigated its anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and on LPS-stimulated systemic inflammation in male ICR mice. Kalopanaxsaponin B inhibited the expression of TNF-α, IL-1β, iNOS and COX-2 in LPS-stimulated peritoneal macrophages. Kalopanaxsaponin B also inhibited the activation of IRAK1, IKK-β, NF-κB and MAP kinases (ERK, JNK, p-38). Treatment with LPS in the presence of kalopanaxsaponin B inhibited LPS-induced IRAK1 degradation and phosphorylation. Kalopanaxsaponin B inhibited IRAK1 kinase binding activity. However, kalopanaxsaponin B did not inhibit the NF-κB activation in active IKK-β-transfected macrophages. Kalopanaxsaponin B did not inhibit the binding of LPS on toll-like receptor-4 of the macrophages. Kalopanaxsaponin B inhibited LPS-induced systemic inflammation in mice. Based on these findings, kalopanaxsaponin B ameliorates LPS-induced systemic inflammation by inhibiting IRAK1 kinase.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Seoul 130 701, Republic of Korea.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Joh
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Jeong
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D034622:RNA Interference; D012503:Saponins / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C064714:kalopanax saponin B; D009828:Oleanolic Acid; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases