Hepatotoxicity of pulegone in rats: Its effects on microsomal enzymes, in vivo

Oral administration of pulegone (400 mg/kg) to rats once daily for five days caused significant decreases in the levels of liver microsomal cytochrome P-450 and heme. Cytochrome b5 and NAD(P)H-cytochrome c-reductase activities were not affected. Massive hepatotoxicy accompanied by an increase in serum glutamate pyruvate transaminase (SGPT) and a decrease in glucose-6-phosphatase were observed upon treatment with pulegone. A significant decrease in aminopyrine N-demethylase was also noticed after pulegone administration. Menthone or carvone (600 mg/kg), compounds related to pulegone, when administered orally did not cause any decrease in cytochrome P-450 levels. The hepatotoxic effects of pulegone were both dose and time dependent. Pretreatment of rats with phenobarbital (PB) or diethylmaleate (DEM) potentiated the hepatotoxicity caused by pulegone, whereas, pretreatment with 3-methylcholanthrene (3-MC) or piperonyl butoxide protected from it. It appears that a PB induced cytochrome P-450 catalysed reactive metabolite(s) may be responsible for the hepatotoxicity caused by pulegone.

In vitro activities of natural products against oral Candida isolates from denture wearers

Background: Candida-associated denture stomatitis is a frequent infectious disease. Treatment of this oral condition is difficult because failures and recurrences are common. The aim of this study was to test the in vitro antifungal activity of pure constituents of essentials oils. -- Methods: Eight terpenic derivatives (carvacrol, farnesol, geraniol, linalool, menthol, menthone, terpinen-4-ol, and aterpineol), a phenylpropanoid (eugenol), a phenethyl alcohol (tyrosol) and fluconazole were evaluated against 38 Candida isolated from denture-wearers and 10 collection Candida strains by the CLSI M27-A3 broth microdilution method. -- Results: Almost all the tested compounds showed antifungal activity with MIC ranges of 0.03-0.25% for eugenol and linalool, 0.03-0.12% for geraniol, 0.06-0.5% for menthol, a-terpineol and terpinen-4-ol, 0.03-0.5% for carvacrol, and 0.06-4% for menthone. These compounds, with the exception of farnesol, menthone and tyrosol, showed important in vitro activities against the fluconazole-resistant and susceptible-dose dependent Candida isolates. -- Conclusions: Carvacrol, eugenol, geraniol, linalool and terpinen-4-ol were very active in vitro against oral Candida isolates. Their fungistatic and fungicidal activities might convert them into promising alternatives for the topic treatment of oral candidiasis and denture stomatitis.

New (1R,4R)-2-arylidene-p-menthan-3-ones with a bridging ester group in the arylidene fragment. Synthesis and behavior in liquid-crystalline systems

(1R,4R)-2-(4-Hydroxybenzylidene)- and (1R,4R)-2-(4′-hydroxybiphenyl- 4-yl)methylene-p-menthan-3-ones were synthesized by condensation of (-)-menthone with O-tetrahydropyran-2-yl derivatives of 4-hydroxybenzaldehyde and 4′-hydroxy-4-formylbiphenyl, respectively, in a DMSO - base medium followed by the removal of the protective group. The reactions of these hydroxy derivatives with 4-alkylbenzoic, 4-alkyloxybenzoic, trans-4-alkylcyclohexane-4- carboxylic, and 4′-alkylbiphenyl-4-carboxylic acids afforded three series of new chiral esters. Compounds containing the arylidene moiety with three benzene rings were found to exhibit liquid-crystalline properties. The characteristic features of these compounds are discussed based on the results of studies by polarizing microscopy, differential scanning calorimetry, and small-angle X-ray scattering. It was found that the mesomorphic compounds under study can form a smectic A mesophase, twist grain boundary mesophases (TGBA), and blue phases in a wide temperature range. Upon dissolution of certain of chiral compounds in 4′-cyano-4-pentylbiphenyl, a rather high twisting power and the thermal stabilizing effect on mesophases were observed.

Supercritical carbon dioxide extraction of bioactive compounds from microalgae and volatile oils from aromatic plants

A discussion of the most interesting results obtained in our laboratories, during the supercritical CO(2) extraction of bioactive compounds from microalgae and volatile oils from aromatic plants, was carried out. Concerning the microalgae, the studies on Botryococcus braunii and Chlorella vulgaris were selected. Hydrocarbons from the first microalgae, which are mainly linear alkadienes (C(23)-C(31)) with an odd number of carbon atoms, were selectively extracted at 313 K increasing the pressure up to 30.0 MPa. These hydrocarbons are easily extracted at this pressure, since they are located outside the cellular walls. The extraction of carotenoids, mainly canthaxanthin and astaxanthin, from C. vulgaris is more difficult. The extraction yield of these components at 313 K and 35.0 MPa increased with the degree of crushing of the microalga, since they are not extracellular. On the other hand, for the extraction of volatile oils from aromatic plants, studies on Mentha pulegium and Satureja montana L were chosen. For the first aromatic plant, the composition of the volatile and essential oils was similar, the main components being the pulegone and menthone. However, this volatile oil contained small amounts of waxes, which content decreased with decreasing particle size of the plant matrix. For S. montana L it was also observed that both oils have a similar composition, the main components being carvacrol and thymol. The main difference is the relative amount of thymoquinone, which content can be 15 times higher in volatile oil. This oxygenated monoterpene has important biological activities. Moreover, experimental studies on anticholinesterase activity of supercritical extracts of S. montana were also carried out. The supercritical nonvolatile fraction, which presented the highest content of the protocatechuic, vanilic, chlorogenic and (+)-catechin acids, is the most promising inhibitor of the enzyme butyrylcholinesterase. In contrast, the Soxhlet acetone extract did not affect the activity of this enzyme at the concentrations tested. (C) 2011 Elsevier B.V. All rights reserved.

Design and synthesis of new monoterpenoid derived ligands for asymmetric catalysis /

The work to be presented herein illustrates several important facts. First, the synthesis of BIBOL (19), a 1,4-diol derived from the monoterpene camphor has allowed us to demonstrate that oxidative dimerizations of enolates can, and do proceed with nearly complete diastereoselectivity under kinetically controlled conditions. The yield of BIBOL is now 50% on average, with a 10% yield of a second diastereomer, which is likely the result of a non-kinetic hydride reduction, thereby affording the epimeric alcohol, 20, coupled on the exo face of camphor. This implies the production of 60% of a single coupling diastereomer. No other diastereomers from the reduction were observed. The utility of BEBOL has been illustrated in early asymmetric additions of diethylzinc to aryl aldehydes, with e.e.'s as high as 25-30%. '^' To further the oxidative coupling work, the same methodology which gave rise to BIBOL was applied to the chiral pool ketone, menthone. Interestingly, this gave an excellent yield of the a-halohydrin (31), which is the result of a chlorination of menthone. This result clearly indicates the high stereoselectivity of the process regardless of the outcome, and has illustrated an interesting dichotomy between camphor and menthone. The utility of the chlorination product as a precursor other chiral ligands is currently being investigated. > ' Finally, a new series of 1,3-diols as well as a new aminoalcohol have successfully been synthesized from highly diastereoselective aldol/mannich reactions. Early studies have indicated their potential in asymmetric catalysis, while employing pi-stack interactions as a means of controlling enantioselective aldol reactions.

Mode of Action of Pulegone on the Urinary Bladder of F344 Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Yield and composition of the essential oil of Mentha piperita L. (Lamiaceae) grown with biosolid

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Níveis de fósforo no desenvolvimento e produção de óleo essencial de Mentha piperita L. cultivada em solução nutritiva

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito alelopático de extrato de leonurus sibiricus l. em mentha piperita l.. desenvolvimento, trocas gasosas e metabólitos do óleo essencial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Physiological indexese macro- and micronutrients in plant tissue and essential oil of Mentha piperita L. grown in nutrient solution with variation in N, P, K and Mg levels

Mentha piperita L. is an aromatic and medicinal species of the family Lamiaceae, known as mint or peppermint, and its leaves and branches produce essential oil rich in menthol. This study aimed to evaluate physiological indexes, macro- and micronutrients inthe shootsand essential oil of Mentha piperita L. grown in nutrient solution number 2 of Hoagland and Arnon (1950) with different N, P, K and Mg levels. Shoot length, dry mass of the different organs, total dry mass, leaf area, essential oil yield and composition, and macronutrient (N, P, K, Mg, Ca, S) and micronutrient (Mn, Cu, Fe, Zn) contents in the shoot were evaluated. Plants treated with 65%N/50%P/25%K/100%Mg had a tendency towards longer shoot, greaterroot and leaf blade dry masses, higher essential oil yield, higher menthol levels and lower menthone levels. The results showed that Mentha can be grown in nutrient solution by reducing 65% N, 50% P, 25% K and 100% Mg. This solution had better development compared to the other tested treatments. Therefore,we recommendMentha piperita L. to be grown with such nutrient levels.

Diurnal effects on mentha canadensis oil concentration and composition at two different harvests

Japanese cornmint, also known as menthol mint (Mentiza canadensis L. syn M. arvensis L.), is an essential oil crop cultivated in several countries in Asia and South America. The plant is currently the only commercially viable source for natural menthol as a result of the high concentration of menthol in the oil compared with other crops. The hypothesis of this study was that harvesting at regular intervals within a 24-hour period would have an effect on essential oil concentration and composition of Japanese cornmint grown at high altitude in northern Wyoming. Flowering plants were harvested every 2 hours on 7 to 8 Aug. and on 14 to 15 Aug. and the essential oil was extracted by steam distillation and analyzed by gas chromatography mass spectroscopy (GC-MS). The effects of harvest date (Harvest 1 and Harvest 2) and harvest time (12 times within a 24-hour period) were significant on oil concentration and yield of menthol, but only harvest date was significant on the concentration of menthol in the oil. The interaction effect of harvest date and harvest time was significant on water content and on the concentrations of menthol and menthofuran in the oil and on the yield of limonene, menthol, and menthofuran. Overall, the oil concentration in grams per 100 g dried material for the two harvests (1.26 and 1.45, respectively), the concentration of menthol in the oil (67.2% and 72.9%, respectively), and menthol yield (1066 to 849 mg/100 g dried biomass) were higher in plants at Harvest 2 as compared with plants at Harvest 1. The oil concentration was higher in plants harvested at 1100 HR or at 1300 am and lowest in the plants harvested at 1500 BR. Menthol yield was the highest in plants harvested at 1300 HR and lowest in the plants harvested at 0700 HR, 1900 am, or at 0300 HR. This study demonstrated that harvesting time within a 24-hour period and harvest date (maturity of the crop) may affect essential oil concentration and composition of Japanese cornmint grown at high altitude in northern Wyoming.

Biomass and essential oil yields of cornmint (Mentha arvensis L.) grown in the irrigation area of Río Dulce, Santiago del Estero, Argentina.

The aim of this study is to determine the yield and composition of the essential oil of cornmint (Mentha arvensis L.) grown in the irrigation area of Santiago del Estero, Argentina. Field tests were carried out under irrigation conditions, harvesting when 70% flowering was reached (in the summer and at the end of the winter seasons). Essential oil yields were 2% in the first cut and 1.6% in the second cut, respectively, the major constituents of the essential oil being menthol, menthone, isomenthone and menthofuran. In both cases, a high concentration of menthol was obtained, although during the winter the content decreased, increasing the concentration of menthofuran. It is concluded that during the summer a higher yield and better quality of essential oil are produced.

Synthèse des fragments de l'ionomycine

L’ionomycine est un ionophore produit par la bactérie gram-positive streptomyces conglobatus. Sa synthèse représente un défi, car il possède plusieurs centres chiraux dans un motif polypropylène. De plus, la grande densité d’oxygène sur celui-ci oblige l’utilisation de plusieurs protections orthogonales. Notre stratégie divise l’ionomycine en quatre fragments, trois possédant le motif polypropylène, ainsi qu’un quatrième, bis-tétrahydrofuranne. Les trois premiers sont synthétisés en utilisant une méthodologie puissante développée dans le laboratoire du Pr Spino, qui utilise l’addition d’alkylcyanocuprates sur les carbonates allyliques dérivés de la menthone. Celle-ci permet l’introduction d’une unité propylène, avec un excellent contrôle du centre chiral introduit. Cette méthode est utilisée de manière itérative, afin d’introduire plusieurs unités propylènes. De plus, notre stratégie est hautement convergente, puisque des intermédiaires des fragments plus courts servent de produit de départ pour la synthèse des fragments plus longs. Le dernier fragment, bis-tétrahydrofuranne, a été fabriqué à partir de l’acétate de géranyle, par une polycyclisation d’un diépoxyde chiral, les époxydes ayant été introduits par une époxydation de Shi. Cette synthèse, si complétée, serait la plus courte publiée, avec 24 étapes pour la séquence linéaire la plus longue (51 au total).