Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages.

Abstract

Seeds of Arctium lappa, containing arctigenin and its glycoside arctiin as main constituents, have been used as a diuretic, anti-inflammatory and detoxifying agent in Chinese traditional medicine. In our preliminary study, arctigenin inhibited IKKβ and NF-κB activation in peptidoglycan (PGN)- or lipopolysaccharide (LPS)-induced peritoneal macrophages. To understand the anti-inflammatory effect of arctigenin, we investigated its anti-inflammatory effect in LPS-stimulated peritoneal macrophages and on LPS-induced systemic inflammation as well as 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Arctigenin inhibited LPS-increased IL-1β, IL-6 and TNF-α expression in LPS-stimulated peritoneal macrophages, but increased LPS-reduced IL-10 and CD204 expression. Arctigenin inhibited LPS-induced PI3K, AKT and IKKβ phosphorylation, but did not suppress LPS-induced IRAK-1 phosphorylation. However, arctigenin did not inhibit NF-κB activation in LPS-stimulated PI3K siRNA-treated peritoneal macrophages. Arctigenin suppressed the binding of p-PI3K antibody and the nucleus translocation of NF-κB p65 in LPS-stimulated peritoneal macrophages. Arctigenin suppressed blood IL-1β and TNF-α level in mice systemically inflamed by intraperitoneal injection of LPS. Arctigenin also inhibited colon shortening, macroscopic scores and myeloperoxidase activity in TNBS-induced colitic mice. Arctigenin inhibited TNBS-induced IL-1β, TNF-α and IL-6 expression, as well as PI3K, AKT and IKKβ phosphorylation and NF-κB activation in mice, but increased IL-10 and CD204 expression. However, it did not affect IRAK-1 phosphorylation. Based on these findings, arctigenin may ameliorate inflammatory diseases, such as colitis, by inhibiting PI3K and polarizing M1 macrophages to M2-like macrophages.

• Authors: Supriya R Hyam, In-Ah Lee, Wan Gu, Kyung-Ah Kim, Jin-Ju Jeong, Se-Eun Jang, Myung Joo Han, Dong-Hyun Kim
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 708 Issue 1-3 Pg. 21-9 (May 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23375938 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Furans
• Lignans
• Lipopolysaccharides
• Phosphoinositide-3 Kinase Inhibitors
• Trinitrobenzenesulfonic Acid
• Peroxidase
• Proto-Oncogene Proteins c-akt
• arctigenin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Colitis (chemically induced, drug therapy, immunology)
• Cytokines (genetics, immunology)
• Furans (pharmacology, therapeutic use)
• Lignans (pharmacology, therapeutic use)
• Lipopolysaccharides
• Macrophages, Peritoneal (drug effects, immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Peroxidase (immunology)
• Phosphatidylinositol 3-Kinases (immunology)
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, immunology)
• Trinitrobenzenesulfonic Acid