Berberine suppresses proinflammatory responses through AMPK activation in macrophages.
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.
Jeong
Hyun Woo
HW
Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, San 56-1, Sillim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
Hsu
Kuan Chi
KC
Lee
Joo-Won
JW
Ham
Mira
M
Huh
Jin Young
JY
Shin
Hyun Jung
HJ
Kim
Woo Sik
WS
Kim
Jae Bum
JB
D041721:3T3-L1 Cells; D000263:Adenylate Kinase / Q000378:metabolism / Q000502:physiology*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D054411:Receptors, Leptin / Q000235:genetics
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D054411:Receptors, Leptin; D001599:Berberine; D000263:Adenylate Kinase