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Berberine suppresses proinflammatory responses through AMPK activation in macrophages
- Source :
- American Journal of Physiology-Endocrinology and Metabolism. 296:E955-E964
- Publication Year :
- 2009
- Publisher :
- American Physiological Society, 2009.
-
Abstract
- 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-α, 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.
- Subjects :
- Male
medicine.medical_specialty
Berberine
Physiology
Adipose Tissue, White
Endocrinology, Diabetes and Metabolism
Anti-Inflammatory Agents
Drug Evaluation, Preclinical
Mice, Obese
Mice, Transgenic
Proinflammatory cytokine
Mice
chemistry.chemical_compound
3T3-L1 Cells
Physiology (medical)
Internal medicine
medicine
Animals
Protein kinase A
Cells, Cultured
Inflammation
chemistry.chemical_classification
Reactive oxygen species
biology
Chemistry
Macrophages
Adenylate Kinase
AMPK
medicine.disease
Adenosine
Mice, Inbred C57BL
Endocrinology
Gene Expression Regulation
Mitogen-activated protein kinase
biology.protein
Receptors, Leptin
Inflammation Mediators
Dyslipidemia
medicine.drug
Subjects
Details
- ISSN :
- 15221555 and 01931849
- Volume :
- 296
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Endocrinology and Metabolism
- Accession number :
- edsair.doi.dedup.....15821b6844a5a3f8bfaad440d6ba6f5e