chemical and Biophysical Research Communications
Volume 388, Issue 2, 16 October 2009, Pages 377-382
Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cellsTeayoun Kima, Jessica Davisa, Albert J. Zhanga, Xiaoming Hea and Suresh T. Mathews, a,
aDepartment of Nutrition and Food Science, Boshell Diabetes and Metabolic Diseases, Research Program, Auburn University, Auburn, AL 36849, USA
Received 27 July 2009. Available online 8 August 2009.
Abstract
Curcumin, the bioactive component of curry spice turmeric, and its related structures possess potent anti-oxidant and anti-inflammatory properties. Several lines of evidence suggest that curcumin may play a beneficial role in animal models of diabetes, both by lowering blood glucose levels and by ameliorating the long-term complications of diabetes. However, current understanding of the mechanism of curcumin action is rudimentary and is limited to its anti-oxidant and anti-inflammatory effects. In this study we examine potential anti-diabetic mechanisms of curcumin, curcumin C3 complex®, and tetrahydrocurcuminoids (THC). Curcuminoids did not exert a direct effect on receptor tyrosine kinase activity, 2-deoxy glucose uptake in L6-GLUT4myc cells, or intestinal glucose metabolism measured by DPP4/α-glucosidase inhibitory activity. We demonstrate that curcuminoids effectively suppressed dexamethasone-induced phosphoenol pyruvate carboxy kinase (PEPCK) and glucose6-phosphatase (G6Pase) in H4IIE rat hepatoma and Hep3B human hepatoma cells. Furthermore, curcuminoids increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase (ACC) in H4IIE and Hep3B cells with 400 times (curcumin) to 100,000 times (THC) the potency of metformin. These results suggest that AMPK mediated suppression of hepatic gluconeogenesis may be a potential mechanism mediating glucose-lowering effects of curcuminoids.
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The Journal of Immunology, 1999, 163: 3474-3483.
Curcumin Blocks Cytokine-Mediated NF-B Activation and Proinflammatory Gene Expression by Inhibiting Inhibitory Factor I-B Kinase Activity1Christian Jobin2,*,, Cynthia A. Bradham*,, Maria Pia Russo*,, Booker Juma§, Acharan S. Narula¶, David A. Brenner*,, and R. Balfour Sartor*,
Departments of * Medicine, Microbiology, and Immunology, Biochemistry and Biophysics, and Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC 27599; § Department of Natural Sciences, Fayettsville State University, Fayettesville, NC, 28301; and ¶ Narula Research, Chapel Hill, NC 27516
Abstract
NF-B plays a critical role in the transcriptional regulation of proinflammatory gene expression in various cells. Cytokine-mediated activation of NF-B requires activation of various kinases, which ultimately leads to the phosphorylation and degradation of IB, the NF-B cytoplasmic inhibitor. The food derivative curcumin has been shown to inhibit NF-B activity in some cell types. In this report we investigate the mechanism of action of curcumin on cytokine-induced proinflammatory gene expression using intestinal epithelial cells (IEC). Curcumin inhibited IL-1ß-mediated ICAM-1 and IL-8 gene expression in IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-B DNA binding activity, RelA nuclear translocation, IB degradation, IB serine 32 phosphorylation, and IB kinase (IKK) activity were blocked by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited by curcumin treatment. In addition, mitogen-activated protein kinase/ERK kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol 12-myristate 13-acetate-responsive element-driven luciferase expression were inhibited by curcumin. However, IB degradation induced by ectopically expressed NF-B-inducing kinase or IKK was not inhibited by curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-B-inducing kinase and IKK. We conclude that curcumin potently inhibits cytokine-mediated NF-B activation by blocking a signal leading to IKK activity.
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Curcumin down-regulates AR gene expression and activation in prostate cancer (37). Inhibitory effects of curcumin on c-Jun/AP-1 and/or NF-κB activation have been observed in both ...
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