Berberine suppresses proinflammatory responses through AMPK activation in macrophages

• Published in: American journal of physiology: endocrinology and metabolism Vol. 296; no. 4; pp. E955 - E964
• Main Authors: Jeong, Hyun Woo, Hsu, Kuan Chi, Lee, Joo-Won, Ham, Mira, Huh, Jin Young, Shin, Hyun Jung, Kim, Woo Sik, Kim, Jae Bum
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.04.2009
• Subjects: 3T3-L1 Cells; Adenylate Kinase - metabolism; Adenylate Kinase - physiology; Adipose Tissue, White - drug effects; Adipose Tissue, White - pathology; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Berberine - pharmacology; Berberine - therapeutic use; Cells, Cultured; Drug Evaluation, Preclinical; Effects; Gene expression; Gene Expression Regulation - drug effects; Inflammation - drug therapy; Inflammation - genetics; Inflammation - pathology; Inflammation Mediators - antagonists & inhibitors; Kinases; Macrophages - drug effects; Macrophages - enzymology; Macrophages - metabolism; Male; Metabolic disorders; Mice; Mice, Inbred C57BL; Mice, Obese; Mice, Transgenic; Receptors, Leptin - genetics; Rodents; Tissues
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.90599.2008

Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, Seoul, Korea Submitted 15 July 2008 ; accepted in final form 3 February 2009 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- , IL-1β, 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-1β, 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. mitogen-activated protein kinase; adenosine 5'-monophosphate-activated protein kinase; reactive oxygen species Address for reprint requests and other correspondence: J. B. Kim, Institute of Molecular Biology and Genetics, Dept. of Biological Sciences, Seoul National Univ., San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea (e-mail: jaebkim{at}snu.ac.kr )