Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Curcumin is a polyphenolic compound possessing interesting anti-inflammatory and antioxidant properties and has the ability to induce the defensive protein heme oxygenase-1 (HO-1). The objective of this study was to investigate whether curcumin protects against cold storage-mediated damage of human adult atrial myoblast cells (Girardi cells) and to assess the potential involvement of HO-1 in this process. Girardi cells were exposed to either normothermic or hypothermic conditions in Celsior preservation solution in the presence or absence of curcumin. HO-1 protein expression and heme oxygenase activity as well as cellular damage were assessed after cold storage or cold storage followed by re-warming. In additional experiments, an inhibitor of heme oxygenase activity (tin protoporphyrin IX, 10 microM) or siRNA for HO-1 were used to investigate the participation of HO-1 as a mediator of curcumin-induced effects. Treatment with curcumin produced a marked induction of cardiac HO-1 in normothermic condition but cells were less responsive to the polyphenolic compound at low temperature. Cold storage-induced damage was markedly reduced in the presence of curcumin and HO-1 contributed to some extent to this effect. Thus, curcumin added to Celsior preservation solution effectively prevents the damage caused by cold-storage; this effect involves the protective enzyme HO-1 but also other not yet identified mechanisms.
Exp Mol Med 2007 Apr 30
PMID:Curcumin reduces cold storage-induced damage in human cardiac myoblasts. 1746 75

Curcumin, a known phytochemical antioxidant was found to be useful as a potential sensor for some small biologically important molecules. Hydrogen peroxide, the sodium salt of nitrite (NO2-), hydroxide (OH-), bromide (Br-) and iodide (I-) were observed to quench the fluorescence of sol-gel encapsulated curcumin, which emits radiation at 530 nm when excited at 420 nm. The observed bimolecular quenching constant which is related to the Stern-Volmer quenching constant, KSV, for the species studied in this work was determined by a modified Stern-Volmer relation for molecular surface accessibility, was observed to be specific for each of these anions and correlates quite well with their half-wave potentials, E1/2. The extent of permeability of these molecules through the pores of the sol-gel matrix was determined and they, also, correlated with these molecules' charge densities and sizes. In all the species, the reaction was quite exergonic and the free energy change, DeltaGoET, obtained in each case, suggest an outer-sphere, long range electron transfer mechanism. These observations open up the possible use of curcumin as a sensor for probing and characterizing some relevant bio-molecules in biological systems.
Cell Mol Biol (Noisy-le-grand) 2007 May 15
PMID:The characterization of the sol-gel encapsulated curcumin as a possible sensor for small biologically important molecules. 1753 Nov 65

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.
Int J Mol Med 2007 Sep
PMID:Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis. 1767 42

(1) Circadian clocks have been localized to discrete sites within the nervous system of several organisms and in mammals to the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN controls and regulates the production and discharge of melatonin (hormonal message of darkness) from the pineal gland via a multisynaptic efferent pathway. The nocturnal rise in melatonin production from serotonin results due to an increased activity of serotonin N-acetyl transferase (NAT). (2) The complex interaction between alcohol and biological clock need to be understood as alcoholism results in various clock linked neuronal disorders especially loss of memory and amnesia like state of consciousness, sleep disorders, insomnia, dementia etc. (3) Serotonin, 5-Hydroxy-tryptamine (5-HT) plays an important role in mediating alcohol's effects on the brain. Understanding the impact of alcohol consumption on circadian system is a pre-requisite to help in treatment of alcohol induced neurological disorders. We, therefore, studied the effect of ethanol drinking and ethanol withdrawal on daily rhythms of serotonin and its metabolite, 5-hydroxy-indole acetic acid (5-HIAA) in SCN and Pineal of adult male Wistar rats maintained under light-dark (LD, 12:12) conditions. (4) Curcumin is well known for its protective properties such as antioxidant, anti-carcinogenic, anti-viral and anti-infectious etc. Hence, we studied the effect of curcumin on ethanol induced changes on 5-HT and 5-HIAA levels and rhythms in SCN and Pineal. (5) Ethanol withdrawal could not restore either rhythmicity or phases or levels of 5-HT and 5-HIAA. Curcumin administration resulted in partial restoration of daily 5-HT/5-HIAA ratio, with phase shifts in SCN and in Pineal. Understanding the impact of alcohol consumption on circadian system and the role of herbal medication on alcohol withdrawal will help in treatment of alcohol induced neurological disorders.
Cell Mol Neurobiol 2007 Dec
PMID:The effect of curcumin on ethanol induced changes in suprachiasmatic nucleus (SCN) and pineal. 1784 84

Curcumin is a polyphenol derived from the dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties. Curcumin has been shown to exhibit an inhibitory effect on the production of inflammatory cytokines by human monocytes and has inhibited the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in association with a decrease in interleukin 12 (IL-12) production and signal transducer and activator of transcription 4 (STAT4) activation. The type I interferon (IFN) IFN-has the ability to suppress IL-12. Both IL-12 and IFN-alpha/beta signal through the activation by phosphorylation of STAT4. Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta. We report that curcumin decreases IL-12-induced STAT4 phosphorylation, IFN-gamma production, and IL-12 Rbeta1 and beta2 expression. IFN-beta-induced STAT4 phosphorylation, IL-10 production and IFN receptor (IFNAR) subunits 1 and 2 expression were enhanced by curcumin. Curcumin increased IFN-alpha-induced IL-10 and IFNAR1 expression. Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation. Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.
J Cell Mol Med
PMID:Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells. 1797 88

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.
Mol Pharm
PMID:Bioavailability of curcumin: problems and promises. 1799 64

We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up-regulated peroxisome proliferator-activated receptor (PPAR)-gamma gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl(4)) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl(4)-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation, and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including interferon-gamma, tumor necrosis factor-alpha, and interleukin-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARgamma and reducing the abundance of platelet-derived growth factor, transforming growth factor-beta, their receptors, and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl(4)-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.
Mol Pharmacol 2008 Feb
PMID:Curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation. 1800 44

Dietary phytochemicals exhibit chemopreventive potential in vivo through persistent low-dose exposures, whereas mechanistic in vitro studies with these agents generally use a high-dose single treatment. Because the latter approach is not representative of an in vivo steady state, we investigated antitumor activity of curcumin, 3,3'-diindolylmethane (DIM), epigallocatechin gallate (EGCG), genistein, or indole-3-carbinol (I3C) in breast cancer MDA-MB-231 cells, exposed in long-term culture to low concentrations, achievable in vivo. Curcumin and EGCG increased cell doubling time. Curcumin, EGCG, and I3C inhibited clonogenic growth by 55% to 60% and induced 1.5- to 2-fold higher levels of the basal caspase-3/7 activity. No changes in expression of cell cycle-related proteins or survivin were found; however, I3C reduced epidermal growth factor receptor expression, contributing to apoptosis. Because some phytochemicals are shown to inhibit DNA and histone modification, modulation of expression by the agents in a set of genes (cadherin-11, p21Cip1, urokinase-type plasminogen activator, and interleukin-6) was compared with changes induced by inhibitors of DNA methylation or histone deacetylation. The phytochemicals modified protein and/or RNA expression of these genes, with EGCG eliciting the least and DIM the most changes in gene expression. DIM and curcumin decreased cadherin-11 and increased urokinase-type plasminogen activator levels correlated with increased cell motility. Curcumin, DIM, EGCG, and genistein reduced cell sensitivity to radiation-induced DNA damage without affecting DNA repair. This model has revealed that apoptosis and not arrest is likely to be responsible for growth inhibition. It also implicated new molecular targets and activities of the agents under conditions relevant to human exposure.
Mol Cancer Ther 2007 Nov
PMID:Extended treatment with physiologic concentrations of dietary phytochemicals results in altered gene expression, reduced growth, and apoptosis of cancer cells. 1802 90

In this study, a cell suspension culture system for zedoary (Curcuma zedoaria Roscoe) was developed, using 50 g/l of fresh weight inoculum in a batch culture. The highest cell biomass obtained from a 5-l bioreactor equipped with three impellers after 14 days of culture was utilized to extract secondary metabolites (essential oil and curcumin) and determine the activities of antioxidant enzymes (peroxidase, superoxide dismutase, and catalase). For essential oil and curcumin, zedoary extracts were recovered via a variety of methods: steam distillation, volatile solvents, and Soxhlet. After 14 days of culture using volatile solvents, the optimal yield of essential oil (1.78%) was obtained when using petroleum ether at 40 degrees C in 6 h of extraction, and the best curcumin yield (9.69%) was obtained at 60 degrees C in 6 h via extraction with 90% ethanol. The activities of antioxidant enzymes from zedoary cells were also assessed. The specific activities of peroxidase, superoxide-dismutase, and catalase reached maximum values of 0.63 U/mg of protein, 16.60 U/mg of protein, and 19.59 U/mg of protein after 14 days of culture, respectively.
Mol Biotechnol 2008 Jan
PMID:Isolation and characterization of antioxidation enzymes from cells of zedoary (Curcuma zedoaria Roscoe) cultured in a 5-l bioreactor. 1804 18

Cytochrome P450 2D6 (CYP2D6), an important CYP isoform with regard to drug-drug interactions, accounts for the metabolism of approximately 30% of all medications. To date, few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo. Six botanical extracts were evaluated in three separate studies (two extracts per study), each incorporating 16 healthy volunteers (eight females). Subjects were randomized to receive a standardized botanical extract for 14 days on separate occasions. A 30-day washout period was interposed between each supplementation phase. In study 1, subjects received milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa). In study 2, kava kava (Piper methysticum) and goldenseal (Hydrastis canadensis) extracts were administered, and in study 3 subjects received St. John's wort (Hypericum perforatum) and Echinacea (Echinacea purpurea). The CYP2D6 substrate, debrisoquine (5 mg), was administered before and at the end of supplementation. Pre- and post-supplementation phenotypic trait measurements were determined for CYP2D6 using 8-h debrisoquine urinary recovery ratios (DURR). Comparisons of pre- and post-supplementation DURR revealed significant inhibition (approximately 50%) of CYP2D6 activity for goldenseal, but not for the other extracts. Accordingly, adverse herb-drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates.
Mol Nutr Food Res 2008 Jul
PMID:Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. 1821 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>