Interaction of curcumin with human serum albumin--a spectroscopic study.

Curcumin (diferuloyl methane) has a wide range of physiological and pharmacological actions. Curcumin interaction with human serum albumin (HSA) has been followed by fluorescence quenching and circular dichroism (CD) measurements. Based on fluorescence measurements, the equilibrium constant for the interaction is 2.0+/-0.2x10(5) M(-1). Binding of curcumin to HSA induces an extrinsic CD band in the visible region. From the induced CD band measurements, the equilibrium constant has a value of 2.1+/-0.3x10(4) M(-1). Thus, HSA has two kinds of affinity sites for curcumin, one with high affinity and the other with lower affinity. Job's plot indicated a binding stoichiometry of 1:1 for the high-affinity site. The equilibrium constant was invariant with temperature in the range of 15 to 45 degrees C, suggesting the role of hydrophobic interactions in the binding of curcumin to HSA. Curcumin does not change the conformation of the HSA molecule. These measurements have implications in the understanding of the curcumin transport under physiological conditions.

Potentiation of cell migration by adhesion-dependent cooperative signals from the GTPase Rac and Raf kinase.

The small GTPase Rac is thought to regulate cell movement by influencing actin cytoskeletal organization and membrane ruffling. However, cell migration also depends on the activation of mitogen-activated protein kinase (MAPK), which can regulate myosin motor function, an event critical for cell contraction. Evidence is provided that, during active cell adhesion to the extracellular matrix, Rac potentiates the MAPK pathway and influences cell migration by selectively synergizing with Raf kinase but not with Ras or MAPK kinase. In fact, the synergy between Rac and Raf kinase increases the chemotactic sensitivity of cells to epidermal growth factor by 1000-fold. Therefore, the role of Rac in cell migration not only depends on its ability to regulate actin cytoskeletal organization but also on its capacity to potentiate chemokine activation of MAPK in a manner that depends on active cell adhesion to the extracellular matrix.

Channelling of intermediates in the biosynthesis of phosphatidylcholine and phosphatidylethanolamine in mammalian cells.

Previous studies with electropermeabilized cells have suggested the occurrence of metabolic compartmentation and Ca2+-dependent channeling of intermediates of phosphatidylcholine (PC) biosynthesis in C6 rat glioma cells. With a more accessible permeabilization technique, we investigated whether this is a more general phenomenon also occurring in other cell types and whether channeling is involved in phosphatidylethanolamine (PE) synthesis as well. C6 rat glioma cells, C3H10T12 fibroblasts and rat hepatocytes were permeabilized with Staphylococcus aureus alpha-toxin, and the incorporation of the radiolabelled precursors choline, phosphocholine (P-choline), ethanolamine and phosphoethanolamine (P-EA) into PC and PE were measured both at high and low Ca2+ concentrations. In glioma cells, permeabilization at high Ca2+ concentration did not affect [14C]choline or [14C]P-choline incorporation into PC. However, reduction of free Ca2+ in the medium from 1.8 mM to <1 nM resulted in a dramatic increase in [14C]P-choline incorporation into permeabilized cells, whereas [14C]choline incorporation remained unaffected. Also, in fibroblasts, reduction of extracellular Ca2+ increased [14C]P-choline and [14C]P-EA incorporation into PC and PE respectively. In hepatocytes, a combination of alpha-toxin and low Ca2+ concentration severely impaired [14C]choline incorporation into PC. Therefore, alpha-toxin-permeabilized hepatocytes are not a good model in which to study channeling of intermediates in PC biosynthesis. In conclusion, our results indicate that channeling is involved in PC synthesis in glioma cells and fibroblasts. PE synthesis in fibroblasts is also at least partly dependent on channeling.

Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats.

Male Wistar rats injected i.p. with 30 mg Fe2+/kg body weight show hepatic damage as measured by an increase in lipid peroxides which correlated with elevated serum enzymes, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH). Oral administration of spice principles, curcumin from turmeric (30 mg/kg body weight) or eugenol from cloves (100 mg/kg body weight), for 10 days lowered the liver and serum lipid peroxide levels, serum ALAT, ASAT and LDH, enhanced by i.p. injection of iron. This study indicates that curcumin or eugenol reduces the iron-induced hepatic damage by lowering lipid peroxidation.

Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron.

The spice principles curcumin (from turmeric) and eugenol (from cloves) are good inhibitors of lipid peroxidation. Lipid peroxidation is known to be initiated by reactive oxygen species. The effect of curcumin and eugenol on the generation of reactive oxygen species in model systems were investigated. Both curcumin and eugenol inhibited superoxide anion generation in xanthine-xanthine oxidase system to an extent of 40% and 50% at concentrations of 75 microM and 250 microM respectively. Curcumin and eugenol also inhibited the generation of hydroxyl radicals (.OH) to an extent of 76% and 70% as measured by deoxyribose degradation. The .OH-radical formation measured by the hydroxylation of salicylate to 2,3-dihydroxy benzoate was inhibited to an extent of 66% and 46%, respectively, by curcumin and eugenol at 50 microM and 250 microM. These spice principles also prevented the oxidation of Fe2+ in Fentons reaction which generates .OH radicals.

Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver.

Male Wistar rats were fed a control diet or the control diet supplemented with 1% (by weight) turmeric for 10 wk. In rats injected with 30 mg Fe2+/kg body weight, lipid peroxidation was 29 and 35% lower in liver homogenates and microsomes, respectively, of turmeric-fed rats than in those of rats fed the control diet. The activities of superoxide dismutase, catalase and glutathione peroxidase were higher (by 19, 19 and 20%, respectively) in liver homogenates of rats fed the turmeric-containing diet in comparison with the controls. These studies indicate that dietary turmeric lowers lipid peroxidation by enhancing the activities of antioxidant enzymes.

Studies on anti-inflammatory activity of spice principles and dietary n-3 polyunsaturated fatty acids on carrageenan-induced inflammation in rats.

The antioxidant spice principles curcumin and eugenol when given by gavage lowered the carrageenan-induced edema in the foot pads of rats. This lowering effect was dependent on the concentration, the time gap between the administration of spice principles and the induction of inflammation by carrageenan. Dietary lipids also influenced the extent of inflammation. Animals fed 10% cod liver oil [containing n-3 polyunsaturated fatty acids (PUFA)] for 10 weeks showed a significantly lower inflammation compared to that observed in animals fed diets supplemented with 10% groundnut oil (rich in n-6 PUFA) or 10% coconut oil (rich in medium-chain saturated fatty acids). Supplementation of diets with 1 weight% of curcumin did not affect the inflammatory responses of animals to carrageenan injection. However, supplementation of diets with 0.17 weight% eugenol further lowered inflammation by 16, 32 and 30% in animals fed coconut oil, groundnut oil and cod liver oil, respectively. Therefore, combinations of dietary lipids with spice principles like eugenol can help in lowering inflammation.

Positioning hospitals: a model for regional hospitals.

In an age of marketing warfare in the health care industry, hospitals need creative strategies to compete successfully. Lately, positioning concepts have been added to the health care marketer's arsenal of strategies. To blend theory with practice, the authors review basic positioning theory and present a framework for developing positioning strategies. They also evaluate the marketing strategies of a regional hospital to provide a case example.

Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes.

Polyunsaturated fatty acids (PUFA) are vulnerable to peroxidative attack. Protecting PUFA from peroxidation is essential to utilize their beneficial effects in health and in preventing disease. The antioxidants vitamin E, t-butylhydroxy toluene (BHT) and t-butylhydroxy anisole (BHA) inhibited ascorbate/Fe(2+)-induced lipid peroxidation in rat liver microsomes. In addition, a number of spice principles, for example, curcumin (5-50 microM) from turmeric, eugenol (25-150 microM) from cloves and capsaicin (25-150 microM) from red chillies inhibited lipid peroxidation in a dose-dependent manner. Zingerone from ginger inhibited lipid peroxidation at high concentrations (greater than 150 microM) whereas linalool (coriander), piperine (black pepper) and cuminaldehyde (cumin) had only marginal inhibitory effects even at high concentrations (600 microM). The inhibition of lipid peroxidation by curcumin and eugenol was reversed by adding high concentrations of Fe2+.