|Zingg, Jean-Marc -|
|Hasan, Syeda -|
|Meydani, Mohsen -|
Submitted to: Biofactors
Publication Type: Review Article
Publication Acceptance Date: October 19, 2012
Publication Date: January 22, 2013
Citation: Zingg, J., Hasan, S.T., Meydani, M. 2013. Molecular mechanisms of hypolipidemic effects of curcumin. Biofactors. 39(1):101-121. Technical Abstract: Recent evidence suggests potential benefits from phytochemicals and micronutrients in reducing the elevated oxidative- and lipid-mediated stress present during inflammation, obesity and atherosclerosis. These compounds may either directly scavenge reactive oxygen or nitrogen species or they may modulate the activity of signal transduction enzymes leading to changes in gene expression. Here we review the proposed molecular mechanisms by which curcumin, a polyphenol derived from the rhizomes of turmeric (Curcuma longa) spice, influences oxidative and lipid-mediated stress in the vascular system. At the molecular level, curcumin can act chemically as scavenger of free radicals. In addition to that increasing experimental evidence suggests that curcumin also influences signal transduction (e.g. Akt, AMPK) and modulates the activity of specific transcription factors (e.g. FOXO1/3a, NRF2, SREBP1/2, CREB, CREBH, PPARgamma, LXRalpha) that regulate the expression of genes involved in free radicals scavenging (e.g. catalase, MnSOD, heme oxygenase-1) and lipid homeostasis (e.g. aP2/FABP4, CD36, HMG-CoA reductase). At the cellular level, curcumin may induce a mild oxidative and lipid-metabolic stress leading to an adaptive cellular stress response by hormetic stimulation of these cellular antioxidant defense and lipid metabolic enzymes. The resulting lower oxidative and lipid-mediated stress may not only explain the beneficial effects of curcumin on inflammation, cardiovascular and neurodegenerative disease, but may also contribute to the increase in maximum life-span observed in animal models.