PMID- 19208854 OWN - NLM STAT- MEDLINE DCOM- 20090521 LR - 20220409 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 296 IP - 4 DP - 2009 Apr TI - Berberine suppresses proinflammatory responses through AMPK activation in macrophages. PG - E955-64 LID - 10.1152/ajpendo.90599.2008 [doi] AB - Berberine (BBR) has been shown to improve several metabolic disorders, such as obesity, type 2 diabetes, and dyslipidemia, by stimulating AMP-activated protein kinase (AMPK). However, the effects of BBR on proinflammatory responses in macrophages are poorly understood. Here we show that BBR represses proinflammatory responses through AMPK activation in macrophages. In adipose tissue of obese db/db mice, BBR treatment significantly downregulated the expression of proinflammatory genes such as TNF-alpha, IL-1beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Consistently, BBR inhibited LPS-induced expression of proinflammatory genes including IL-1beta, IL-6, iNOS, MCP-1, COX-2, and matrix metalloprotease-9 in peritoneal macrophages and RAW 264.7 cells. Upon various proinflammatory signals including LPS, free fatty acids, and hydrogen peroxide, BBR suppressed the phosphorylation of MAPKs, such as p38, ERK, and JNK, and the level of reactive oxygen species in macrophages. Moreover, these inhibitory effects of BBR on proinflammatory responses were abolished by AMPK inhibition via either compound C, an AMPK inhibitor, or dominant-negative AMPK, implying that BBR would downregulate proinflammatory responses in macrophages via AMPK stimulation. FAU - Jeong, Hyun Woo AU - Jeong HW AD - Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea. FAU - Hsu, Kuan Chi AU - Hsu KC FAU - Lee, Joo-Won AU - Lee JW FAU - Ham, Mira AU - Ham M FAU - Huh, Jin Young AU - Huh JY FAU - Shin, Hyun Jung AU - Shin HJ FAU - Kim, Woo Sik AU - Kim WS FAU - Kim, Jae Bum AU - Kim JB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090210 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Inflammation Mediators) RN - 0 (Receptors, Leptin) RN - 0I8Y3P32UF (Berberine) RN - EC 2.7.4.3 (Adenylate Kinase) SB - IM MH - 3T3-L1 Cells MH - Adenylate Kinase/metabolism/*physiology MH - Adipose Tissue, White/drug effects/pathology MH - Animals MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - Berberine/*pharmacology/therapeutic use MH - Cells, Cultured MH - Drug Evaluation, Preclinical MH - Gene Expression Regulation/drug effects MH - Inflammation/drug therapy/genetics/pathology MH - Inflammation Mediators/*antagonists & inhibitors MH - Macrophages/*drug effects/enzymology/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Obese MH - Mice, Transgenic MH - Receptors, Leptin/genetics EDAT- 2009/02/12 09:00 MHDA- 2009/05/22 09:00 CRDT- 2009/02/12 09:00 PHST- 2009/02/12 09:00 [entrez] PHST- 2009/02/12 09:00 [pubmed] PHST- 2009/05/22 09:00 [medline] AID - 90599.2008 [pii] AID - 10.1152/ajpendo.90599.2008 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E955-64. doi: 10.1152/ajpendo.90599.2008. Epub 2009 Feb 10.