title: 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: Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Supriya R
authors: SR
authors: Hyam
authors: In-Ah
authors: IA
authors: Lee
authors: Wan
authors: W
authors: Gu
authors: Kyung-Ah
authors: KA
authors: Kim
authors: Jin-Ju
authors: JJ
authors: Jeong
authors: Se-Eun
authors: SE
authors: Jang
authors: Myung Joo
authors: MJ
authors: Han
authors: Dong-Hyun
authors: DH
authors: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D017705:Lignans / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005663:Furans; D017705:Lignans; D008070:Lipopolysaccharides; D009195:Peroxidase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D014302:Trinitrobenzenesulfonic Acid; C071942:arctigenin