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: Eun-Ha Joh, Jin-Ju Jeong, Dong-Hyun Kim
• Journal: Cellular immunology (Cell Immunol) Vol. 279 Issue 1 Pg. 103-8 (Sep 2012) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 23117333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012. Published by Elsevier Inc.

Chemical References

• Drugs, Chinese Herbal
• Interleukin-1beta
• Lipopolysaccharides
• NF-kappa B
• Saponins
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• kalopanax saponin B
• Oleanolic Acid
• Nitric Oxide Synthase Type II
• Ptgs2 protein, mouse
• Cyclooxygenase 2
• Interleukin-1 Receptor-Associated Kinases
• Irak1 protein, mouse
• I-kappa B Kinase
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Blotting, Western
• Cells, Cultured
• Cyclooxygenase 2 (metabolism)
• Drugs, Chinese Herbal (pharmacology)
• Enzyme Activation (drug effects)
• I-kappa B Kinase (genetics, metabolism)
• Inflammation (chemically induced, metabolism, prevention & control)
• Interleukin-1 Receptor-Associated Kinases (genetics, metabolism)
• Interleukin-1beta (metabolism)
• Lipopolysaccharides (toxicity)
• Macrophages, Peritoneal (cytology, drug effects, metabolism)
• Male
• Mice
• Mice, Inbred ICR
• Microscopy, Confocal
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Oleanolic Acid (analogs & derivatives, pharmacology)
• RNA Interference
• Saponins (pharmacology)
• Toll-Like Receptor 4 (metabolism)
• Transfection
• Tumor Necrosis Factor-alpha (metabolism)