Molecular mechanisms of hypolipidemic effects of curcumin

Abstract

Recent evidence suggests potential benefits from phytochemicals and micronutrients in reducing the elevated oxidative and lipid-mediated stress associated with 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 the expression of antioxidant genes. Alternatively, they may reduce plasma lipid levels by modulating lipid metabolic genes in tissues and thus reduce indirectly lipid-mediated oxidative and endoplasmic reticulum stress through their hypolipidemic effect. Here we review the proposed molecular mechanisms by which curcumin, a polyphenol present in the rhizomes of turmeric (Curcuma longa) spice, influences oxidative and lipid-mediated stress in the vascular system. At the molecular level, mounting experimental evidence suggests that curcumin may act chemically as scavenger of free radicals and/or influences signal transduction (e.g., Akt, AMPK) and modulates the activity of specific transcription factors (e.g., FOXO1/3a, NRF2, SREBP1/2, CREB, CREBH, PPARγ, and LXRα) that regulate the expression of genes involved in free radicals scavenging (e.g., catalase, MnSOD, and heme oxygenase-1) and lipid homeostasis (e.g., aP2/FABP4, CD36, HMG-CoA reductase, and carnitine palmitoyltransferase-I (CPT-1)). 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 systems 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.

Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis

“…This observation is consistent with previous findings that curcumin treatment inhibits lipid-induced ER stress 14 and diabetes-induced ER stress in the adult heart 27 . In our previous studies, we have elucidated a critical role of ER stress in hyperglycemia-induced NTD formation 20, 28 .…”

“…Curcumin is a potent antioxidant which has been shown to suppress diabetes-induced superoxide in vascular endothelial cells 13 . In addition to its antioxidant properties, curcumin appears to be able to modulate signal transduction and gene expression 14 . A previous study has demonstrated that curcumin blocks diabetes-induced inducible nitric oxide synthase (iNOS) expression in the adult heart 15 .…”

Application of a Novel Curcumin Analog in the Management of Diabetic Cardiomyopathy

“…In addition, curcumin is also commonly used as a coloring and flavoring additive in foods. Recent studies indicate that dietary administration of curcumin may be effective in treating conditions such as cancer, Alzheimer disease, and cystic fibrosis (14,15). With regards to the mode of action, curcumin exerts a rather diverse array of metabolic, cellular, and molecular activities (15).…”

“…Recent studies indicate that dietary administration of curcumin may be effective in treating conditions such as cancer, Alzheimer disease, and cystic fibrosis (14,15). With regards to the mode of action, curcumin exerts a rather diverse array of metabolic, cellular, and molecular activities (15). However, certain pharmacokinetic defects, such as low bioavailability and fast metabolism, and poor chemical stability significantly limit the clinical application of curcumin.…”

The effects of multi-strain probiotics on liver disease

“…However, recent research has suggested that the effects of curcumin at lower concentrations which are achieved in vivo are independent of its antioxidant properties and are via signal transduction and gene expression. 257,258 Indeed, treatment was associated with changes in the gene expression of proteins involved in fatty acid oxidation. Of interest, the gene expression of AdipoR2 was attenuated in Hfe -/-mice fed a HFD consistent with previous observations.…”