rosmanol and carnosol

Recently, rosemary extracts standardized to diterpenes (e.g. carnosic acid and carnosol) have been approved by the European Union (EU) and given a GRAS (Generally Recognized as Safe) status in the United States by the Food and Drug Administration (FDA). Incorporation of rosemary into our food system and through dietary selection (e.g. Mediterranean Diet) has increased the likelihood of exposure to diterpenes in rosemary. In consideration of this, a more thorough understanding of rosemary diterpenes is needed to understand its potential for a positive impact on human health. Three agents in particular have received the most attention that includes carnosic acid, carnosol, and rosmanol with promising results of anti-cancer activity. These studies have provided evidence of diterpenes to modulate deregulated signaling pathways in different solid and blood cancers. Rosemary extracts and the phytochemicals therein appear to be well tolerated in different animal models as evidenced by the extensive studies performed for approval by the EU and the FDA as an antioxidant food preservative. This mini-review reports on the pre-clinical studies performed with carnosic acid, carnosol, and rosmanol describing their mechanism of action in different cancers.

Topics: Abietanes; Animals; Antineoplastic Agents, Phytogenic; Diterpenes; Humans; Neoplasms; Phytotherapy; Plant Extracts; Plants, Medicinal; Rosmarinus; Signal Transduction

Topics: Abietanes; Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Biomarkers; Cytokines; Disease Management; Disease Models, Animal; Disease Susceptibility; Drug Synergism; Inflammation Mediators; Male; Mice; Molecular Structure; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Plant Extracts; Signal Transduction; Toll-Like Receptor 4

Carnosic acid (CA) and derived diterpenes abundant in rosemary extracts (REs) exert anti-obesity effects. The aim of this study was to investigate the bioavailability of these compounds in a rat model of obesity.. A total of 26 compounds were tentatively identified based on accurate mass information and the isotopic pattern provided by TOF-MS analyzer. The main metabolites detected in the gut content, liver, and plasma were the glucuronide conjugates of CA, carnosol, and rosmanol. Two other metabolites were also identified: CA 12-methyl ether and 5,6,7,10-tetrahydro-7-hydroxyrosmariquinone. All the metabolites were detected as early as 25 min following oral administration. Most of the compounds remained in the intestine, liver, and (or) plasma at substantial concentrations for several hours supporting their potential health benefits in these tissues. We also corroborated the presence of small quantities of CA and detected trace quantities of the main CA metabolites in the brain. Notably, we did not find significant differences in the metabolic profile between lean and obese rats.. We report for the first time a comprehensive profile of metabolites in various organs following the oral consumption of an RE enriched in CA and contribute to establish the potential bioactive molecules.

Topics: Abietanes; Animals; Biological Availability; Brain; Chromatography, Liquid; Diterpenes; Female; Glucuronides; Intestinal Mucosa; Intestines; Liver; Metabolome; Oils, Volatile; Plant Extracts; Rats; Rats, Zucker; Rosmarinus; Tandem Mass Spectrometry

The new aromatic diterpenes 7beta-O-benzylrosmanol (3), 7beta-O-benzyl-11,12-di-O-methylrosmanol (4), and 7alpha-thiophenylcarnosic acid (5) have been obtained by partial synthesis from carnosol (1), an abundant natural diterpene present in Salvia species. The structures of these compounds were established from their physical and spectroscopic data. The known diterpenes sagequinone methide A (6), 7beta-O-methylrosmanol (7), 7-O-methylrosmanol (8), and rosmaquinone B (9) were obtained from rosmanol (2). The spectroscopic data of these semisynthetic diterpenes were identical to data reported in the literature. In addition, the new semisynthetic isorosmaquinone (10) was obtained from isorosmanol (12). The proton resonances of rosmaquinone (11) are reassigned based on 2D NMR spectroscopy. These compounds, as well as eight known analogues, were evaluated for cytotoxic and antimicrobial activities.

Topics: Abietanes; Animals; Antineoplastic Agents, Phytogenic; Chlorocebus aethiops; Diterpenes; Drug Screening Assays, Antitumor; Gram-Negative Bacteria; Gram-Positive Bacteria; HeLa Cells; Humans; Microbial Sensitivity Tests; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plants, Medicinal; Quinones; Salvia; Structure-Activity Relationship; Vero Cells

Subcritical water extraction at several temperatures ranging from 25 to 200 degrees C has been studied to selectively extract antioxidant compounds from rosemary leaves. An exhaustive characterization of the fractions obtained using subcritical water at different temperatures has been carried out by LC-MS, and the antioxidant activities of the extracts have been measured by a free radical method (DPPH). Results indicate high selectivity of the subcritical water toward the most active compounds of rosemary such as carnosol, rosmanol, carnosic acid, methyl carnosate, and some flavonoids such as cirsimaritin and genkwanin. The antioxidant activity of the fractions obtained by extraction at different water temperatures was very high, with values around 11.3 microg/mL, comparable to those achieved by SFE of rosemary leaves. A study of the effect of the temperature on the extraction efficiency of the most typical rosemary antioxidant compounds has been performed.

Topics: Abietanes; Antioxidants; Chromatography, High Pressure Liquid; Chromatography, Liquid; Diterpenes; Flavonoids; Mass Spectrometry; Molecular Structure; Phenanthrenes; Plant Extracts; Plant Leaves; Rosmarinus; Temperature; Water

The antioxidant activity of aqueous infusions of sage emerges from specific components present in that herb. In an attempt to investigate the chemical nature and properties of these components, four organic solvent extracts from aqueous infusions of sage were examined. HPLC analyses of these extracts led to the separation of a number of components, of which four were identified and quantified through the use of standard compounds of known chromatographic HPLC profiles. These compounds are the diterpenes carnosic acid, carnosol, and rosmanol and the hydroxycinnamic acid caffeic acid. The antioxidant activity and polyphenol content were determined in the four organic solvent extracts and the left-over aqueous fraction. Both polyphenolic and nonpolyphenolic substances present in the extracts arise as significant contributors to the observed antioxidant activity of the derived extracts and thus sage itself. In this sense, they reflect the antioxidant potential of the aqueous infusions of sage toward reactive oxygen species generated through variable mechanisms of iron-promoted oxidative processes.

Topics: Abietanes; Antioxidants; Caffeic Acids; Chromatography, High Pressure Liquid; Diterpenes; Flavonoids; Phenanthrenes; Phenols; Plant Extracts; Polyphenols; Salvia officinalis; Water

The known diterpenes rosmanol (3), rosmaquinone (4), 7-methoxyrosmanol (5), 7-ethoxyrosmanol (6), galdosol (7), and epirosmanol (8) have been obtained by partial synthesis from carnosol (2), an abundant natural product present in Salvia species. The physical and spectroscopic data of these semisynthetic diterpenes were identical to those of authentic natural samples and with data reported in the literature. These abietane diterpenes have very interesting biological activities and are present in the genus Salviain low quantities; thus, the semisynthetic approach described here represents an efficient alternative method to obtain these compounds. Additionally, the known diterpene 16-hydroxyrosmanol (10) and a new aromatic diterpene 11 were obtained from 16-hydroxycarnosol (9) by reaction with Ph3P/NBS in CH2Cl2. The structure of the new compound 11 was established from its spectroscopic data as 12,16-epoxycarnosol.

Topics: Abietanes; Catalysis; Diterpenes; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Oxidation-Reduction; Phenanthrenes; Plant Extracts; Plant Leaves; Plants, Medicinal; Salvia

Carnosol 1, rosmanol 2, carnosic acid 3 and 20-deoxocarnosol 4, the main phenolic abietanes present in aerial parts of the Chilean medicinal plant Sphacele salviae were tested for antioxidant activity of measuring the decay of the radical cation diphenyl-picrylhydrazyl (DPPH). All compounds displayed higher antioxidant levels than BHT under the same conditions and carnosic acid was more efficient than vitamin E.

Topics: Abietanes; Antioxidants; Biphenyl Compounds; Butylated Hydroxytoluene; Chile; Diterpenes; Dose-Response Relationship, Drug; Lamiaceae; Medicine, Traditional; Phenanthrenes; Picrates; Plant Extracts; Plant Leaves; Plants, Medicinal; Structure-Activity Relationship; Time Factors; Vitamin E

To investigate the inhibition capacities of carnosol, rosmanol, and epirosmanol, which are phenolic diterpenes from Rosmarinus officinalis, to oxidized low-density lipoprotein (LDL) formation in human blood and detect their scavenging activities to lipid free radical and superoxide anion in vitro.. The antioxidant activities which were expressed with the inhibilities to lipid free radicals in the membrane lipid of cell and oxidized LDL formation were evaluated by TBARS assay and ESR method. The inhibition on the Cu2+-mediated oxidization of apo B formation in LDL was investigated by fluorescence spectroscopy.. Carnosol, rosmanol, and epirosmanol had an inhibitory activity to lipid peroxidation and oxidized apo B formation in human bloods LDL. The IC50 were 7-10 micromol/L. The antioxidant mechanism was related to the scavenging activities to lipid free radical.. carnosol, rosmanol, and epirosmanol showed the activity in inhibiting LDL oxidation.

Topics: Abietanes; Antioxidants; Cell Membrane; Diterpenes; Free Radicals; Humans; Hydroxybenzoates; Lipid Peroxidation; Lipoproteins, LDL; Phenanthrenes; Rosmarinus; Superoxides

In order to find new effective HIV protease inhibitors, two diterpenes (carnosic acid [1] and carnosol [5]) were isolated from rosemary (Rosmarinus officinalis L.), and rosmanol [2] and semisynthetic derivatives (7-O-methylrosmanol [3], 7-O-ethylrosmanol [4], and 11,12-O,O-dimethylcarnosol [6]) were prepared. The inhibitory activity of all six compounds against HIV-1 protease was tested. The carnosic acid [1] showed the strongest inhibitory effect (IC90 = 0.08 micrograms/ml). The same compound was also assayed against HIV-1 virus replication (IC90 = 0.32 micrograms/ml). The cytotoxic TC90 on H9 lymphocytes was 0.36 micrograms/ml, which is very close to the effective antiviral dose. Additionally, the tested compounds did not inhibit cellular aspartic proteases cathepsin D and pepsin at the concentration range up to 10 micrograms/ml [corrected].

Topics: Abietanes; Animals; Cathepsin D; Cattle; Cell-Free System; HIV Protease Inhibitors; HIV-1; Humans; Pepsin A; Phenanthrenes; Plants, Medicinal; Virus Replication