Showing papers on "Carnosic acid published in 2001"
TL;DR: Carnosic acid enhances a program of gene expression consistent with 1alpha,25(OH)2D3-, ATRA-, or TPA-induced monocytic differentiation of HL60-G cells, which enhances the expression of several cell cycle-associated proteins.
Abstract: BACKGROUND Carnosic acid is a plant-derived polyphenol food preservative with chemoprotective effects against carcinogens when tested in animals. Recently, we showed that carnosic acid potentiates the effects of 1alpha,25-dihydroxyvitamin D3 (1alpha,25[OH]2D3) and of all-trans-retinoic acid (ATRA) on differentiation of human leukemia cells. We now examine the mechanisms associated with carnosic acid-induced enhancement of cell differentiation (in subline HL60-G) initiated by 1alpha,25(OH)2D3, ATRA, or 12-O-tetradecanoylphorbol-13-acetate (TPA). METHODS We evaluated monocytic differentiation markers (CD11b, CD14, and monocytic serine esterase), cell cycle parameters, and cell proliferation rates after treatment of cells with different agents with or without carnosic acid. We also assessed the abundance of the vitamin D receptor (VDR), retinoid X receptor (RXR)-alpha, retinoic acid receptor (RAR)-alpha, and cell cycle-associated proteins by immunoblot analysis (p27, early growth response gene [EGR]-1, and p35Nck5a), the expression of corresponding genes by reverse transcription-polymerase chain reaction (RT-PCR), and the activity of VDR by electrophoretic mobility shift analysis. The two-sided nonparametric Kruskal-Wallis one-way analysis-of-variance test with Dunn's adjustment was used for statistical analyses. RESULTS Monocytic differentiation induced by low (1 nM) concentrations of 1alpha,25(OH)2D3, ATRA, or TPA was enhanced by carnosic acid (10 microM), as shown by the increased expression of monocytic serine esterase (P<.001, P<.001, and P =.043, respectively) and of CD11b (P =.008, P =.046, and P =.041, respectively). Increased expression of CD14 was seen only for 1alpha,25(OH)2D3 and ATRA (P =.009 and P =.048, respectively) and also for several cell cycle-associated proteins. Carnosic acid in combination with 1alpha,25(OH)2D3 and ATRA resulted in decreased cell proliferation and blocked the cell cycle transition from G1 to S phase (P<.05). Carnosic acid alone increased the expression of VDR and RXR-alpha, but the expression was greatly enhanced in the presence of 1alpha,25(OH)2D3 and ATRA. In combination with TPA, carnosic acid potentiated the expression of VDR and RAR-alpha. CONCLUSION Carnosic acid enhances a program of gene expression consistent with 1alpha,25(OH)2D3-, ATRA-, or TPA-induced monocytic differentiation of HL60-G cells.
105 citations
TL;DR: The results indicate that carnosic acid is capable of antiproliferative action in leukemic cells and can cooperate with other natural anticancer compounds in growth-inhibitory and differentiating effects.
Abstract: Carnosic acid, the polyphenolic diterpene derived from rosemary, is a strong dietary antioxidant that exhibits antimutagenic properties in bacteria and anticarcinogenic activity in various cell and animal models. In the present study, we show that carnosic acid (2.5-10 microM) inhibits proliferation of HL-60 and U937 human myeloid leukemia cells (half-maximal inhibitory concentration = 6-7 microM) without induction of apoptotic or necrotic cell death. Growth arrest occurred concomitantly with a transient cell cycle block in the G1 phase, which was accompanied by an increase in the immunodetectable levels of the universal cyclin-dependent kinase inhibitors p21WAFI and p27Kipl. Carnosic acid caused only a marginal induction of differentiation, as monitored by the capacity to generate superoxide radicals and the expression of cell surface antigens (CD11b and CD14) and receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine. However, at low concentrations, this polyphenol substantially augmented (100- to 1,000-fold) the differentiating effects of 1,25-dihydroxyvitamin D3 and all-trans retinoic acid. Furthermore, such combinations of carnosic acid and any of these differentiation inducers synergistically inhibited proliferation and cell cycle progression. These results indicate that carnosic acid is capable of antiproliferative action in leukemic cells and can cooperate with other natural anticancer compounds in growth-inhibitory and differentiating effects.
99 citations
TL;DR: In this article, the same mechanism of antioxidative protection by carnosic acid applies in rosemary and sage, and shows that it is the complete set of antioxidants that is responsible for avoiding drought-induced damage in plants.
89 citations
TL;DR: In this paper, the authors extracted rosemary and sage leaves with hexane, acetone, ethyl acetate and ethanol and found that the antioxidant activity was about the same in rapeseed oil as in sunflower oil, but substantially lower than that in lard.
Abstract: Rosemary and sage leaves were extracted with hexane, acetone, ethyl acetate and ethanol. Yields of extracts and of carnosic acid contents were higher in solvents of medium polarity. Both carnosic acid and carnosol showed medium activity in deodorized rapeseed oil, about the same as that of butylated hydroxyanisole. Carnosic acid was moderately more active than carnosol, and the resulting oxidative stability of extracts was correlated with the content of carnosic acid, but not with the content of carnosol. The antioxidant activity was about the same in rapeseed oil as in sunflower oil, but substantially lower than that in lard. Antioxidant activities, expressed as protection factors, were higher under Schaal oven test conditions at 40 or 60C than when determined in Oxipres at 100C. The dependence of the concentration of antioxidants and the protection factor showed similar negative exponential relations in all tests.
35 citations
Patent•
1 Feb 2001
TL;DR: In this paper, a composition containing a stabilized form of conjugated linoleic acid is described, in which the conjugation of linolenic acid with glycerol is reacted to form an ester, which is much more resistant to oxidation than the acid form of the compound.
Abstract: A composition containing a stabilized form of conjugated linoleic acid is described. The conjugated linoleic acid is reacted with glycerol to form an ester, which is much more resistant to oxidation than the acid form of the conjugated linoleic acid. The composition can additionally contain antioxidants, such as rosemary leaf extract, tocopherols, chelating agents, ascorbic acid, the like. The composition can also contain a fatty acid and/or glycerol ingredient. A method for supplementing an individual's diet is also described.
12 citations
Patent•
2 Mar 2001TL;DR: In this paper, a chewing gum rubber composition (gum base) that utilizes carnosic acid from a Libiatae plant such as rosemary or sage, as an antioxidant stabilizer was revealed.
Abstract: This invention discloses a chewing gum rubber composition (gum base) that utilizes carnosic acid from a Libiatae plant, such as rosemary or sage, as an antioxidant stabilizer. This invention more specifically discloses a chewing gum base comprising: (1) about 5 weight percent to about 95 weight percent of a rubbery elastomer; (2) about 0 weight percent to about 75 weight percent of an elastomer plasticizer selected from the group consisting of natural rosin esters and synthetic terpene resins; (3) about 1 weight percent to about 65 weight percent of a filler material; and (4) carnosic acid, wherein said chewing gum base is void of sweeteners, flavoring agents or colors.
5 citations
Journal Article•
TL;DR: The 10-vinyl-8,11,13-podocatriene 8, which is a model of Carnosic acid type diterpenes, has been synthesized by an expeditious convergent synthetic approach as discussed by the authors.
5 citations
Patent•
28 Aug 2001
TL;DR: In this article, a dip for preserving fish is described, which includes lactic acid, sodium phosphate, cultured dextrose, vitamin C, vitamin E7, carnosic acid, rosamarinic acid and citric acid.
Abstract: The present invention is a dip for preserving fish. It includes the following ingredients: lactic acid, sodium phosphate, cultured dextrose, vitamin C, vitamin E7, carnosic acid, rosamarinic acid, citric acid and honey and salt. The dip may be provided in a liquid, for example, water, and used as a bath.
3 citations
Patent•
28 Feb 2001
TL;DR: A novel carnosic acid derivative for promoting the synthesis of nerve growth factor (NGF) was proposed in this article, which can safely and efficiently promote the production of NGF in the living body, without being accompanied by a side effect such as a loss of a quantitative balance of hormones.
Abstract: A novel carnosic acid derivative for promoting the synthesis of nerve growth factor (NGF), a composition comprising the carnosic acid derivative as an effective ingredient, as well as, a method of promoting the synthesis of NGF comprising administering an effective amount of the carnosic acid derivative as an effective ingredient to a subject requiring such promotion. The carnosic acid derivative, composition and method according to the present invention can safely and efficiently promote the production of NGF in the living body, without being accompanied by a side effect such as a loss of a quantitative balance of hormones in the living body.
1 citations
Patent•
26 Jan 2001
TL;DR: A chewing gum base comprises 5-95 % rubbery elastomer, 0-75 % elastic plasticizer selected from natural rosin esters and synthetic terpene resins, 1-65 % filler material, and carnosic acid as mentioned in this paper.
Abstract: A chewing gum base comprises 5-95 % rubbery elastomer, 0-75 % elastomer plasticizer selected from natural rosin esters and synthetic terpene resins, 1-65 % filler material, and carnosic acid. A chewing gum also comprises a sweetner and a flavour, and the rubbery elastomer in an alternative chewing gum is styrene-butadiene with a bound styrene content of 1-10 % and RPA t 80 of at least 0.06 minutes. An alternative invention of a stabilized rubber comprises a rubbery polymer and carnosic acid. The inventions utilize carnosic acid from a Libiatae plant, such as rosemary or sage, as an antioxidant stabilizer.
TL;DR: Three apianane terpenoids, rel-(5S, 6S, 7S, 10R, 12S, 13R)-7-hydroxyapiana-8,14-diene-11,16-dion-(22,6)-olide, were isolated from the leaves of Salvia officinalis together with 15 known compounds.
TL;DR: From a quantitative time course analysis of the production of these quinones, an antioxidant mechanism of carnosic acid is proposed, consisting of the oxidative coupling reaction with the peroxyl radical at the 12- or 14-position of carnsic acid and subsequent degradation reactions.
Abstract: To determine the antioxidant mechanism of food phenolics against the oxidation of food components, the reaction of carnosic acid, an antioxidative constituent of the popular herbs sage and rosemary, was investigated in the presence of ethyl linoleate and the radical oxidation initiator 2,2‘-azobis(2,4-dimethylvaleronitrile). During this process, carnosic acid was oxidized to an o-quinone and a hydroxy p-quinone, the chemical structures of which were confirmed by physical and chemical techniques. From a quantitative time course analysis of the production of these quinones, an antioxidant mechanism of carnosic acid is proposed, consisting of the oxidative coupling reaction with the peroxyl radical at the 12- or 14-position of carnosic acid and subsequent degradation reactions. Keywords: Carnosic aid; antioxidant mechanism; radical termination; sage; Labiatae; o-quinone
TL;DR: Subcellular localization studies show that carnosic acid protects chloroplasts from oxidative stress in vivo by following a highly regulated compartmentation of oxidation products.
Abstract: The potent antioxidant properties of rosemary (Rosmarinus officinalis) extracts have been attributed to its major diterpene, carnosic acid. Carnosic acid has received considerable attention in food science and biomedicine, but little is known about its function in the plant in vivo. We recently found that highly oxidized diterpenes increase in rosemary plants exposed to drought and high light stress as a result of the antioxidant activity of carnosic acid (S. Munne-Bosch, K. Schwarz, L. Alegre [1999] Plant Physiol 121: 1047-1052). To elucidate the significance of the antioxidant function of carnosic acid in vivo we measured the relative amounts of carnosic acid and its metabolites in different compartments of rosemary leaves. Subcellular localization studies show that carnosic acid protects chloroplasts from oxidative stress in vivo by following a highly regulated compartmentation of oxidation products. Carnosic acid scavenges free radicals within the chloroplasts, giving rise to diterpene alcohols, mainly isorosmanol. This oxidation product is O-methylated within the chloroplasts, and the resulting form, 11,12-di-O-methylisorosmanol, is transferred to the plasma membrane. This appears to represent a mechanism of a way out for free radicals from chloroplasts. Carnosic acid also undergoes direct O-methylation within the chloroplasts, and its derived product, 12-O-methylcarnosic acid, accumulates in the plasma membrane. O-methylated diterpenes do not display antioxidant activity, but they may influence the stability of the plasma membrane. This study shows the relevance of the compartmentation of carnosic acid metabolism to the protection of rosemary plants from oxidative stress in vivo.