title: Inhibitory effects of berberine on lipopolysaccharide-induced inducible nitric oxide synthase and the high-mobility group box 1 release in macrophages.
abstract: We investigated the molecular mechanism by which berberine reduces nitric oxide (NO) expression and high-mobility group box 1 (HMGB1) release in lipopolysaccharide (LPS)-induced macrophages. Berberine significantly inhibited the LPS-stimulated NO production and HMGB1 release in macrophages. In addition, berberine also induced heme oxygenase (HO)-1 in a dose-dependent manner, which was mediated through activation of p38 MAPK and NF-E2-related factor 2 (Nrf2) signaling cascade in macrophages. The inhibitory effect of berberine on LPS-stimulated NO and HMGB1 release was reversed by siRNA-Nrf2, SB203580 (p38 MAPK inhibitor) and zinc protoporphyrin (ZnPP; HO-1 inhibitor) within macrophages. Therefore, we conclude that berberine inhibits the proinflammatory response to LPS in macrophages by up-regulation of the HO-1 level, in which p38 MAPK and Nrf2 have an important role. These results suggest that berberine may be useful as a therapeutic agent for the treatment of inflammatory diseases.
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors: Danbi
authors: D
authors: Lee
authors: Jinbum
authors: J
authors: Bae
authors: Yoon Kyu
authors: YK
authors: Kim
authors: Minchan
authors: M
authors: Gil
authors: Joo-Yong
authors: JY
authors: Lee
authors: Chan-Sik
authors: CS
authors: Park
authors: Kyung Jin
authors: KJ
authors: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics; D008070:Lipopolysaccharides; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D001599:Berberine; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4