Abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand activated transcription factor, belonging to the metazoan family of nuclear hormone receptors. Activation of PPARgamma increases the transcription of enzymes involved in primary metabolism, leading to lower blood levels of fatty acids and glucose. Hence, PPARgamma represents the major target for the glitazone type of drugs currently being used clinically for the treatment of type 2 diabetes. Furthermore, activators of PPARgamma show beneficial anti-inflammatory and anti-tumour effects. Utilizing a fusion receptor of the yeast Gal4-DNA binding domain joined to the hinge region and ligand binding domain of the human PPARgamma in combination with a Gal4-driven luciferase reporter gene, cotransfected into Cos7 cells, we tested sage and rosemary extracts prepared with 80 % aqueous ethanol for possible PPARgamma activation. This revealed that both extracts are capable of selectively activating Gal4-PPARgamma fusion receptor, in a concentration-dependent manner, with EC (50) values of 22.8 +/- 8.4 mg/L and 33.7 +/- 7.3 mg/L for rosemary and sage, respectively. Subsequent analysis of the characteristic constituents revealed the phenolic diterpene compounds carnosol, present in both herbs, and carnosic acid to be active principles of these extracts, showing EC (50) values of 41.2 +/- 5.9 microM and 19.6 +/- 2.0 microM, respectively. Thus it can be concluded that the glucose lowering effect reported recently for rosemary may be attributed to PPARgamma activation. Moreover, our observations may also explain the anti-inflammatory and antiproliferative effects of both compounds published previously.

Abstract: The peroxisome proliferator-activated receptors play a pivotal role in metazoan lipid and glucose homeostasis. Synthetic activators of PPARalpha (fibrates) and PPARgamma (glitazones) are therefore widely used for treatment of dislipidemia and diabetes, respectively. There is growing evidence for herbal compounds to influence nuclear receptor signalling e.g. the PPARs. We recently reported carnosic acid and carnosol, both being diterpenes found in the labiate herbs sage and rosemary, to be activators of PPARgamma. The subsequent screening of a variety of ethanolic extracts, obtained from traditionally used herbs, for PPAR activation, led to an exceptionally high hit rate. Among 52 extracts nearly the half significantly activated PPARgamma and 14 activated PPARalpha in addition, whereas three of them were pan-PPAR activators, which also activated PPARdelta. The most active extracts, for which a concentration dependent effect could be shown, were the extracts of Alisma plantago aquatica (ze xie/european waterplantain), Catharanthus roseus (madagascar periwinkle), Acorus calamus (sweet calamus), Euphorbia balsamifera (balsam spurge), Jatropha curcas (barbados nut), Origanum majorana (marjoram), Zea mays (corn silk), Capsicum frutescens (chilli) and Urtica dioica (stinging nettle). The results of the present study provide a possible rationale for the traditional use of many herbs as antidiabetics.

Abstract: The radioprotective effects of carnosic acid (CA), carnosol (COL), and rosmarinic acid (RO) against chromosomal damage induced by γ-rays, compared with those of l-ascorbic acid (AA) and the S-containing compound dimethyl sulfoxide (DMSO), were determined by use of the micronucleus test for antimutagenic activity, evaluating the reduction in the frequency of micronuclei (MN) in cytokinesis-blocked cells of human lymphocytes before and after γ-ray irradiation. With treatment before γ-irradiation, the most effective compounds were, in order, CA > RO ≥ COL > AA > DMSO. The radioprotective effects (antimutagenic) with treatment after γ-irradiation were lower, and the most effective compounds were CA and COL. RO and AA presented small radioprotective activity, and the sulfur-containing compound DMSO lacked γ-ray radioprotection capacity. Therefore, CA and COL are the only compounds that showed a significant antimutagenic activity both before and after γ-irradiation treatments. These results are closely related ...

Abstract: The antioxidant and antimicrobial effects of commercially available oil-soluble rosemary extracts VivOX 20 and VivOX 4 were investigated against lipid oxidation and microbial growth in vacuum-packed chicken frankfurters. The content of the main active ingredient, carnosic acid, in extracts was 20% and 4% (w/w), respectively. For comparison, the activity of commercially available preservative Robin LI LS was also tested. The control was chicken frankfurters made without test additives. Antioxidant activity tests were performed at 3 storage temperatures (4, 12, 25 °C), using the Rancimat method. Antimicrobial effect was investigated by aerobic plate count. Results showed that both rosemary preparations possess antioxidant and antimicrobial properties that may make them useful in the food industry. In chicken frankfurters with added VivOX 20 and VivOX 4, higher oxidative stability was exhibited at all storage temperatures, as in frankfurters with Robin LI LS. Addition of VivOX 20, VivOX 4, and Robin LI LS also significantly reduced the aerobic plate count, compared to controls, stored at 4 or 12 °C.

Abstract: 1alpha,25-dihydroxyvitamin D(3) (1,25D(3)) is a powerful differentiation agent, which has potential for treatment of myeloid leukemias and other types of cancer, but the calcemia produced by pharmacologically active doses precludes the use of this agent in the clinic. We have shown that carnosic acid, the major rosemary polyphenol, enhances the differentiating and antiproliferative effects of low concentrations of 1,25D(3) in human myeloid leukemia cell lines (HL60, U937). Here we translated these findings to in vivo conditions using a syngeneic mouse leukemia tumor model. To this end, we first demonstrated that as in HL60 cells, differentiation of WEHI-3B D(-) murine myelomonocytic leukemia cells induced by 1 nM 1,25D(3) or its low-calcemic analog, 1,25-dihydroxy-16-ene-5,6-trans-cholecalciferol (Ro25-4020), can be synergistically potentiated by carnosic acid (10 microM) or the carnosic acid-rich ethanolic extract of rosemary leaves. This effect was accompanied by cell cycle arrest in G0 + G1 phase and a marked inhibition of cell growth. In the in vivo studies, i.p. injections of 2 microg Ro25-4020 in Balb/c mice bearing WEHI-3B D(-) tumors produced a significant delay in tumor appearance and reduction in tumor size, without significant toxicity. Another analog, 1,25-dihydroxy-16,23Z-diene-20-epi-26,27-hexafluoro-19-nor-cholecalciferol (Ro26-3884) administered at the same dose was less effective than Ro25-4020 and profoundly toxic. Importantly, combined treatment with 1% dry rosemary extract (mixed with food) and 1 microg Ro25-4020 resulted in a strong cooperative antitumor effect, without inducing hypercalcemia. These results indicate for the first time that a plant polyphenolic preparation and a vitamin D derivative can cooperate not only in inducing leukemia cell differentiation in vitro, but also in the antileukemic activity in vivo. These data may suggest novel protocols for chemoprevention or differentiation therapy of myeloid leukemia.

Abstract: The effects of rosmarinic acid and a rosemary antioxidant powder were evaluated on the reduction and mutagenicity of MeIQx, PhIP, and comutagens norharman and harman in beef patties fried at 375 °F for 5 min each side and 400 °F for 7.5 min each side. Both rosemary extracts were found to effectively decrease the formation and overall mutagenic activity of heterocyclic amines (HCAs) due to their antioxidative characteristics. At the lower temperature, rosmarinic acid was able to reduce MeIQx by up to 64% and PhIP by 48%, while rosemary powder reduced the formations of MeIQx up to 69% and PhIP up to 66%. The effects of the rosemary extracts were more dramatic when cooking temperature and time were increased, as rosmarinic acid was able to reduce MeIQx formation up to 70% and PhIP up to 64%; also, rosemary powder significantly reduced MeIQx up to 57% and PhIP up to 77%. The overall mutagenic activity was evaluated by the Ames Salmonella assay and both rosemary extracts were capable of reducing mutagenicity in beef patties at the higher cooking temperature of 400 °F. At 375 °F there was an insignificant trend of the rosemary extracts decreasing the number of Salmonella revertants. There was no significant inhibiting effect by any of the rosemary extracts on the formation of either norharman and harman as measured in this study.

Abstract: A phytochemical study has been carried out on the aerial parts of Salvia pachyphylla and S. clevelandii. From S. pachyphylla, the known diterpenes carnosol (2), rosmanol, 20-deoxocarnosol (3), carnosic acid, isorosmanol (4), 7-methoxyrosmanol, 5,6-didehydro-O-methylsugiol (5), 8β-hydroxy-9(11),13-abietadien-12-one (6), 11,12-dioxoabieta-8,13-diene, and 11,12-dihydroxy-20-norabieta-5(10),8,11,13-tetraen-1-one were isolated, together with the new diterpene pachyphyllone (1). From S. clevelandii, the known diterpenes rosmadial (7), 16-hydroxycarnosol (8), abieta-8,11,13-triene, and taxodone were obtained, together with carnosol (2), rosmanol, and carnosic acid. The structure of the new compound (1) was identified on the basis of spectroscopic data analysis. Several of these compounds (1−8) were evaluated against a small panel of human cancer cell lines.

Abstract: The demand for novel effective antioxidant-based drugs has led to the synthesis and evaluation of the antioxidant potential in several molecules derived from natural compounds. In this work the in vitro antioxidant activity of an abietic acid-derived catechol (methyl 11,12-dihydroxyabietate-8,11,13-trien-18-oate, MDTO) was evaluated. This substance, possessing important biological properties, is similar to carnosic acid, a natural antioxidant from rosemary or sage leaves. Aiming to understand the antioxidant activity of MDTO, the energetics of its O-H bond, using time-resolved photoacoustic calorimetry (TR-PAC), was investigated. On energetic grounds it is predicted that MDTO is a good free radical scavenger, although its activity is lower than that of quercetin, a very effective antioxidant, which was used for comparison. In agreement with these predictions, the DPPH(*) and ABTS(*+) radical scavenging activities are lower than those of quercetin. In addition, MDTO also reacts with HOCl, a powerful proinflammatory oxidant produced by activated neutrophils, and protects liposomes against iron-ascorbate-induced oxidation. The discussion of these results foresees potential applications of MDTO as an antioxidant.

Abstract: The bacteriocin nisin is active against both food spoilage and foodborne pathogenic Gram-positive bacteria. Previous studies have demonstrated that nisin activity can be enhanced in combination with chelating agents, certain emulsifiers and essential oils of herbs. Such combined food protection solutions offer the benefits of a multiple hurdle system, which gives better prevention of the emergence of less sensitive organisms and which may also reduce the required dosage of a single preservative. The present investigation examined the combination of nisin with natural extracts of the herb rosemary (Rosmarinus officinalis) containing high levels of antioxidant phenolic diterpenes and low levels of flavour compounds such as essential oils. In vitro testing demonstrated such a combination to be synergistic. The rosemary extracts enhanced both the cidal and static antibacterial activities of nisin against Gram-positive bacteria. Comparative testing with differently processed extracts identified the phenolic diterpenes carnosol and carnosic acid as the primary synergists. The synergism was demonstrated against Listeria monocytogenes and Bacillus cereus in vitro and in chilled, pasteurised food models (chicken soup, meat and cheese pasta sauces). The effect was increased by low temperature and acid conditions.

Abstract: Different culture types (shoot culture, callus culture, and cell suspension culture) of Rosmarinus officinalis L. were established and their ability to biosynthesize the phytochemicals carnosic acid, carnosol, and rosmarinic acid were assessed and compared with subcultures of the same stem plant over time. Furthermore, we examined the antioxidative effect of extracts from different culture types by measuring their scavenging activity on 1,1diphenyl-2-picrylhydrazyl (DPPH) radicals as well as their anti-inflammatory potential on neonatal microglial rat cells activated by means of the inflammogen lipopolysaccharide (LPS) taking nitric oxide (NO) as parameter. Our results show that during an investigation period of 17 months, the shoot culture accumulated varying amounts of carnosic acid and carnosol, which were also present in callus culture but about 20- to 80-fold lower than in the shoot culture. In suspension culture, only carnosic acid and no carnosol could be detected. The level of carnosic acid in suspension culture was threefold less than detected for the callus culture on average. The amount of rosmarinic acid produced in shoot culture and callus culture were comparable, whereas in suspension culture higher concentrations of rosmarinic acid could be measured than in shoot and callus culture. Thus, the content of carnosic acid, carnosol, and rosmarinic acid in the extracts depended on the differentiation grade of the cell culture type. The DPPH radical-scavenging activity of the extracts depended on the amount of all three phytochemicals, in particular of rosmarinic acid. The anti-inflammatory character of the extracts was mainly based on their carnosic acid content.

Abstract: Rosmarinus officinalis L. presents a high genetic variability, which is reflected in the chemical composition of the different individuals, and consequently in its biological activity, including an...

Abstract: Food supplement comprises gamma-tocopherol, flavonoids, carnosic acid and carnosol. ACTIVITY : Tranquilizer; Nootropic; Dermatological. MECHANISM OF ACTION : None given. No biological data given.

Abstract: The following review summarizes the roles of natural antioxidants and antimicrobials in food protection and safety, with reference to certain commercial products. It is important such products have reliable activity in the target food systems and that their activity can be quantified; methods used for assay are reviewed. The most common natural antioxidants at present are those based on tocopherols or extracted from plants, particularly extracts of the herb rosemary (Rosmarinus officinalis L). The main antioxidant components in rosemary are the phenolic diterpenes carnosol and carnosic acid. The bacteriocin nisin is also described: a natural antimicrobial produced by fermentation of Lactococcus lactis subsp. lactis that is effective against Gram positive bacteria. Natamycin is also reviewed: a polyene macrolide produced by fermentation of the bacterium Streptomyces natalensis with broad spectrum activity against molds and yeasts.

Abstract: A method for the determination of carnosic acid and carnosol in supercritical fluid extract(SFE) of Rosemary by HPLC was developed.The SFE sample was extracted with 100 mL of methanol in an ultrasonic bath at room temperature for 30 min.After filtering with the membrane(0.5 μm),the liquid was analyzed by HPLC using Nova pak C_(18)(150 mm×3.9 mm) as the stationary phase and 0.01 mol/mL acetonitrile-water(52∶48 by volume) as the mobile phase at a flow rate of 0.8(mL/min).The detected wavelength was 285 nm.The linear ranges of the calibration curves for carsonic acid and carnosol were 0.1-50 mg/L and 0.5-50 mg/L,respectively,the correlation coefficients were 0.999 8 and 0.999 6,respectively,the detection limits were 0.1 and 0.8 mg/L,respectively,and the average recoveries were 98% and 95%,respectively.