beta-carotene and salvin

Multidrug resistance is a principal mechanism by which tumors become resistant to structurally and functionally unrelated anticancer drugs. Resistance to chemotherapy has been correlated with overexpression of p-glycoprotein (p-gp), a member of the ATP-binding cassette (ABC) superfamily of membrane transporters. P-gp mediates resistance to a broad-spectrum of anticancer drugs including doxorubicin, taxol, and vinca alkaloids by actively expelling the drugs from cells. Use of specific inhibitors/blocker of p-gp in combination with clinically important anticancer drugs has emerged as a new paradigm for overcoming multidrug resistance. The aim of this paper is to review p-gp regulation by dietary nutraceuticals and to correlate this dietary nutraceutical induced-modulation of p-gp with activity of anticancer drugs.

Topics: Abietanes; Alkaloids; Allyl Compounds; Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B; Benzodioxoles; beta Carotene; Biflavonoids; Capsaicin; Catechin; Catechols; Curcumin; Dietary Supplements; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Fatty Alcohols; Furocoumarins; Humans; Indoles; Limonins; Neoplasms; Phytotherapy; Piperidines; Polyunsaturated Alkamides; Proanthocyanidins; Quercetin; Resveratrol; Stilbenes; Sulfides; Tea; Triterpenes; Xanthophylls

Inflammatory mediators and cytokines play important roles in the pathogenesis of a vast number of human diseases; therefore much attention is focused on blunting their proinflammatory modes of action. The aims of the present research were to assess the effectiveness of combinations of carotenoids and phenolics, at concentrations that can be achieved in blood, to inhibit the release of inflammatory mediators from macrophages exposed to lipopolysaccharide (LPS) and to determine what the anti-inflammatory effect of the phytonutrient combinations was in an in vivo mouse model of peritonitis. Preincubation of mouse peritoneal macrophages with lycopene (1 μM) or Lyc-O-Mato (1 μM) and carnosic acid (2 μM), lutein (1 μM), and/or β-carotene (2 μM) 1h before addition of LPS for 24 h caused a synergistic inhibition of NO, prostaglandin E(2), and superoxide production derived from downregulation of iNOS, COX-2, and NADPH oxidase protein and mRNA expression and synergistic inhibition of TNFα secretion. We surmise that the anti-inflammatory action of the phytonutrient combinations used probably resides in their antioxidant properties, because they caused an immediate, efficient, and synergistic inhibition of LPS-induced internal superoxide production leading to a marked decrease in ERK and NF-κB activation. The anti-inflammatory effects of the selected phytonutrient combinations were also demonstrated in a mouse model of peritonitis: their supplementation in drinking water resulted in attenuation of neutrophil recruitment to the peritoneal cavity and in inhibition of inflammatory mediator production by peritoneal neutrophils and macrophages.

Topics: Abietanes; Animals; Anti-Inflammatory Agents, Non-Steroidal; beta Carotene; Carotenoids; Cells, Cultured; Cyclooxygenase 2; Dinoprostone; Drug Synergism; Gene Expression Regulation; Lipopolysaccharides; Lutein; Lycopene; Macrophages, Peritoneal; Male; Mice; Mice, Inbred ICR; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type II; Oxidation-Reduction; Peritonitis; Plant Extracts; Signal Transduction; Superoxides; Tumor Necrosis Factor-alpha

Methods were developed to identify and select accessions of rosemary, Rosmarinus officinalis (L.), producing optimum antioxidant activity. Extracts from 12 different rosemary accessions, using three solvents of varying polarity, were assayed for their antioxidant activity, and their major antioxidant compounds were identified and quantified by high-performance liquid chromatography (HPLC). Carnosic acid concentrations were correlated with (i) the free radical scavenging activity of these extracts, as measured by the 2,2-diphenyl-1-picrylhydrazyl assay (adjusted R(2) = 77.3%) and (ii) their inhibition of linoleic acid oxidation, as measured by the beta-carotene assay (adjusted R(2) = 44.1%). The correlation was broadly confirmed by the production of volatile aldehydes as measured by the hexanal assay. The variation of carnosic acid concentrations in extracts of 29 accessions, grown in field trials at three sites in England, was determined.

Topics: Abietanes; Antioxidants; beta Carotene; Chromatography, High Pressure Liquid; Diterpenes; Free Radical Scavengers; Lipid Peroxidation; Plant Extracts; Rosmarinus

The photoprotective potential of the dietary antioxidants vitamin C, vitamin E, lycopene, beta-carotene, and the rosemary polyphenol, carnosic acid, was tested in human dermal fibroblasts exposed to ultraviolet-A (UVA) light. The carotenoids were prepared in special nanoparticle formulations together with vitamin C and/or vitamin E. Nanoparticle formulations, in contrast to dimethylsulphoxide, stablized lycopene in the cell culture medium and allowed efficient cellular uptake. The presence of vitamin E in the formulation further increased the stability and cellular uptake of lycopene. UVA irradiation of the human skin fibroblasts led to a 10-15-fold rise in metalloproteinase 1 (MMP-1) mRNA. This rise was suppressed in the presence of low microM concentrations of vitamin E, vitamin C, or carnosic acid but not with beta-carotene or lycopene. Indeed, in the presence of 0.5-1.0 microM beta-carotene or lycopene, the UVA-induced MMP-1 mRNA was further increased by 1.5-2-fold. This increase was totally suppressed when vitamin E was included in the nanoparticle formulation. Heme-oxygenase 1 (HO-1) mRNA expression was strongly induced by UVA irradiation but none of the antioxidants inhibited this effect at the concentrations used in this study. Indeed, beta-carotene or lycopene (0.5-1.0 microM) led to a further 1.5-fold rise in the UVA-induced HO-1 mRNA levels. In conclusion, vitamin C, vitamin E, and carnosic acid showed photoprotective potential. Lycopene and beta-carotene did not protect on their own but in the presence of vitamin E, their stability in culture was improved and the rise in MMP-1 mRNA expression was suppressed, suggesting a requirement for antioxidant protection of the carotenoids against formation of oxidative derivatives that can influence the cellular and molecular responses.

Topics: Abietanes; Adult; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Blotting, Northern; Carotenoids; Cells, Cultured; Chromatography, High Pressure Liquid; Cytoprotection; Diterpenes; DNA Damage; Fibroblasts; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Lycopene; Male; Matrix Metalloproteinase 1; Membrane Proteins; Plant Extracts; Radiation-Protective Agents; Skin; Ultraviolet Rays; Vitamin E