Kalopanaxsaponin B inhibits LPS-induced inflammation by inhibiting IRAK1 Kinase.

Eun-Ha Joh, Jin-Ju Jeong, Dong-Hyun Kim

Index: Cell. Immunol. 279(1) , 103-8, (2012)

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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.Copyright © 2012. Published by Elsevier Inc.