Zaluzania montagnifolia: essential oil composition and biological properties / Zaluzania montagnifolia: composición del aceite esencial y actividades biológicas

The chemical composition of the seasonal essential oils (2015-2016) from the leaves and flowers of Zaluzania montagnifolia is presented. The chemical content of those oils showed quantitative and qualitative differences. Germacrene D (19.9-29.8%), camphor (12.4- 19.4%) and ß-caryophyllene (13.7-18.5%) were the most abundant volatiles in the leaves. The essential oils from the flowers contained high amounts of camphor (32.7-37.2%) limonene (19.8-24.9%) and germacrene D (3.2-7.3%). All the seasonal essential oils showed a potent in vitro inhibition against HMG-CoA reductase. The essential oils from flowers (IC50, 40.5-55.1 µg mL-1) showed better inhibition properties than those of leaves (IC50, 84.4-123.5 µg mL-1). Camphor (IC50, 72.5 µg mL-1) and borneol (IC50, 84.4 µg mL-1) exerted a non-competitive inhibition on the enzyme. Additionally, the hydrodistillates exhibited antibacterial activity against the phytopathogenic Pseudomonas syringae pv. tabaci TBR2004 (MIC, 62.7-76.5 µg mL-1) P. syringae pv. tomato DC3000 (MIC, 45.4-50.4 µg mL-1) and P. syringae pv. phaseolicola NPS3121 (MIC, 26.7-31.9 µg mL-1). Germacrene D (MIC, 35.4-66.2 µg mL-1) and ß-caryophyllene (MIC, 36.5-54.2 µg mL-1) were the strongest anti-Pseudomonas syringae agents.

Se presenta la composición química de los aceites esenciales estacionales (2015-2016) provenientes de hojas y flores de Zaluzania montagnifolia. El contenido químico de los aceites esenciales mostró diferencias cualitativas y cuantitativas. El germacreno D (19.9-29.8%), alcanfor (12.4-19.4%) y ß-cariofileno (13.7-18.5%) fueron los volátiles más abundantes en las hojas. Los aceites esenciales de las flores contuvieron altas concentraciones de alcanfor (32.7-37.2%), limoneno (19.8-24.9%) y germacreno D (3.2-7.3%). Todos los aceites esenciales estacionales mostraron una potente inhibición in vitro contra la HMG-CoA reductasa. Los aceites esenciales de las flores (IC50, 40.5-55.1 µg mL-1) mostraron mejores propiedades inhibitorias que aquellos de las hojas (IC50, 84.4-123.5 µg mL-1). El alcanfor (IC50, 72.5 µg mL-1) y el borneol (IC50, 84.4 µg mL-1) ejercieron una inhibición no competitiva sobre la enzima. Adicionalmente, los hidrodestilados exhibieron una actividad antibacterial contra los fitopatógenos Pseudomonas syringae pv. tabaci TBR2004 (MIC, 62.7-76.5 µg mL-1) P. syringae pv. tomato DC3000 (MIC, 45.4-50.4 µg mL-1) y P. syringae pv. phaseolicola NPS3121 (MIC, 26.7-31.9 µg mL-1). El germacreno D (MIC, 35.4-66.2 µg mL-1) y ß-cariofileno (MIC, 36.5-54.2 µg mL-1) fueron los agentes más fuertes contra los patovares de Pseudomonas syringae.

The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta

The relaxant effect of the methyl ester of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g, 6 rats for each experimental group) with and without endothelium precontracted with 1.0 µM phenylephrine. The methyl ester presented a slightly greater potency than rosuvastatin in relaxing aortic rings, with log IC50 values of -6.88 and -6.07 M, respectively. Unlike rosuvastatin, the effect of its methyl ester was endothelium-independent. Pretreatment with 10 µM indomethacin did not inhibit, and pretreatment with 1 mM mevalonate only modestly inhibited the relaxant effect of the methyl ester. Nω-nitro-L-arginine methyl ester (L-NAME, 10 µM), the selective nitric oxide-2 (NO-2) inhibitor 1400 W (10 µM), tetraethylammonium (TEA, 10 mM), and cycloheximide (10 µM) partially inhibited the relaxant effect of the methyl ester on endothelium-denuded aortic rings. However, the combination of TEA plus either L-NAME or cycloheximide completely inhibited the relaxant effect. Inducible NO synthase (NOS-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with methyl ester-treated rings. In conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme A reductase in rat aorta, the methyl ester of rosuvastatin exhibited an endothelium-independent and only slightly hydroxymethylglutaryl coenzyme A reductase-dependent relaxant effect. Both NO produced by NOS-2 and K+ channels are involved in the relaxant effect of the methyl ester of rosuvastatin.

The methyl ester of rosuvastatin elicited an endothelium-independent and 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent relaxant effect in rat aorta.

The relaxant effect of the methyl ester of rosuvastatin was evaluated on aortic rings from male Wistar rats (250-300 g, 6 rats for each experimental group) with and without endothelium precontracted with 1.0 µM phenylephrine. The methyl ester presented a slightly greater potency than rosuvastatin in relaxing aortic rings, with log IC50 values of -6.88 and -6.07 M, respectively. Unlike rosuvastatin, the effect of its methyl ester was endothelium-independent. Pretreatment with 10 µM indomethacin did not inhibit, and pretreatment with 1 mM mevalonate only modestly inhibited the relaxant effect of the methyl ester. Nω-nitro-L-arginine methyl ester (L-NAME, 10 µM), the selective nitric oxide-2 (NO-2) inhibitor 1400 W (10 µM), tetraethylammonium (TEA, 10 mM), and cycloheximide (10 µM) partially inhibited the relaxant effect of the methyl ester on endothelium-denuded aortic rings. However, the combination of TEA plus either L-NAME or cycloheximide completely inhibited the relaxant effect. Inducible NO synthase (NOS-2) was only present in endothelium-denuded aortic rings, as demonstrated by immunoblot with methyl ester-treated rings. In conclusion, whereas rosuvastatin was associated with a relaxant effect dependent on endothelium and hydroxymethylglutaryl coenzyme A reductase in rat aorta, the methyl ester of rosuvastatin exhibited an endothelium-independent and only slightly hydroxymethylglutaryl coenzyme A reductase-dependent relaxant effect. Both NO produced by NOS-2 and K+ channels are involved in the relaxant effect of the methyl ester of rosuvastatin.

Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture of very long chain saturated fatty acids.

The present study was undertaken to investigate the effects of D003, a mixture of very long chain saturated fatty acids isolated and purified from sugar cane wax, on cholesterol biosynthesis in cultured fibroblasts. Cholesterol biosynthesis is regulated through feedback regulation of at least two sequentially acting enzymes, 3-hydroxy-3-methyl coenzyme A (HMG-CoA) synthase and reductase. They are up-regulated when sterol levels fall and down-regulated when sterol levels rise. The exposure of cultured fibroblasts to a lipid-depleted medium (LDM) and D003 (0.05-50 microg ml(-1)) for 12 h inhibited, in a dose-dependent manner, cholesterol biosynthesis from 14C-labelled acetate (33-68%). The addition of D003 at concentrations inhibiting cholesterol biosynthesis from labelled acetate significantly decreased incorporation of radioactivity from 3H2O into sterols, but not from 14C-mevalonate. These data indicate that D003 inhibits cholesterol biosynthesis by interfering with early steps of cholesterol biosynthetic pathway. We reasoned that D003 acts directly on HMG-CoA reductase, the main regulatory enzyme of cholesterol biosynthetic pathway. However, when enzyme activity was measured in cell extracts in the presence of various concentrations of D003 (0.5-50 microg ml(-1)), reductase activity was not inhibited. Thus, there was no evidence for a competitive or non-competitive inhibition of enzyme activity by D003. Treatment with D003 significantly suppressed (68%) the enzyme up-regulation when cells were cultured in LDM, which suggests a depression of de novo synthesis of HMG-CoA reductase and/or a stimulation of its degradation. However, since the suppressive action of D003 on cholesterol biosynthesis was observed in metabolic conditions under which synthase up-regulation was also enhanced, we cannot rule out a possible effect of D003 on HMG-CoA synthase. Thus, further studies are needed to clarify the precise mechanism of the inhibitory effect of D003 on cholesterol biosynthesis.

Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats.

We have suggested previously, measuring 14C-acetate incorporation into free cholesterol, that oral administration of policosanol inhibits hepatic cholesterol biosynthesis in rats. Nevertheless, since acetate has limitations to study cholesterol synthesis in vivo, we now investigate rates of incorporation of labeled water into hepatic sterol after policosanol treatment. Absolute rates of incorporation of 3H-water in sterols were depressed by policosanol by about 20%, giving a more accurate degree of cholesterol biosynthesis inhibition in this species. Since policosanol did not inhibit labeled mevalonate incorporation into cholesterol in rat liver, we also studied the effect of policosanol on hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase. Reductase activity assayed in microsomes treated with policosanol remained unchanged, suggesting that cholesterol synthesis is not inhibited by a direct action of policosanol on this enzyme.

Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats

We have suggested previously, measuring 14C-acetate incorporation into free cholesterol, that oral administration of policosanol inhibits hepatic cholesterol biosynthesis in rats. Nevertheless, since acetate has limitations to study cholesterol synthesis in vivo, we now investigate rates of incorporation of labeled water into hepatic sterol after policosanol treatment. Absolute rates of incorporation of 3H-water in sterols were depressed by policosanol by about 20 percent, giving a more accurate degree of cholesterol biosynthesis inhibition in this species. Since policosanol did not inhibit labeled mevalonate incorporation into cholesterol in rat liver, we also studied the effect of policosanol on hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase. Reductase activity assayed in microsomes treated with policosanol remained unchanged, suggesting that cholesterol synthesis is not inhibited by a direct action of policosanol on this enzyme

Estatinas no tratamento da hipercolesterolemia / Statins in the hypercholesterolemia treatment

Estatinas säo drogas derivadas de microorganismos e que eficientemente interferem na síntese celular de colesterol por inibiçäo competitiva da enzima HMG-CoA-redutase. Näo obstante, as estatinas reduzem a colesterolemia por induzirem formaçäo de receptores que captam as LDL do plasma e por diminuirem a síntese de VLDL no fígado. Esta última explica o efeito parcial na queda da trigliceridemia. A eficiência das estatinas na diminuiçäo da colesterolemia é comparável à das resinas seqüestradoras de ácidos biliares, porém superios à dos fibrates e ácido nicotínico. Estatinas säo melhor toleradas do que estas últimas duas drogas, mas inferiores quanto à capacidade de diminuirem os triglicérides e de aumentarem o HDL-colesterol. Seletividade tissular varia entre as diversas estatinas, mas esta é uma questäo irrelevante tendo em vista a raridade dos efeitos colaterais. Conseqüentemente, estas drogas devem ser prescritas em razäo da potência farmacológica e do fator custo. Cinecoronarioangiografia seqüencial em pacientes com coronariopatia tratados com placebo em comparaçäo a estatinas isoladamente, indica que a doença arterial regride por métodos farmacológicos.

As açöes dos inibidores da HMG CoA redutase säo influenciadas por variaçöes do peso corpóreo? Estudo com a pravastatina / The actions of reductase HMG CoA inhibitors were influenced with body weight variations? Study with pravastatin

Dispondo dos resultados do estudo multicêntrico que avaliou a eficácia da pravastatina em pacientes com hipercolesterolemia primária, os AA investigaram se a intensidade das respostas guardava ligaçäo com a variaçäo do peso corpóreo, ocorrida em 12 semanas de observaçäo. Foi analisado o comportamento das variáveis lipídicas (CT, TG, HDL-C, VLDL-C e LDL-C em tres grupos de pacientes: G1 - 308 pacientes que tiveram elevaçäo do peso corpóreo superior a 5 por cento: G2 - 1.250 pacientes com oscilaçöes entre - 5 e + 5 por cento: G3 - 162 pacientes que tiveram reduçäo do peso superior a 5 por cento. A análise comparativa entre os grupos mostrou que o G3 teve reduçöes significativamente maiores de CT,LDL-C E TG e nesse mesmo grupo houve freqüência de indivíduos que atingiram valores desejáveis de LDL-C e CT. Entre os G1 e G2 näo foram observadas diferenças significativas, embora açäo da pravastatina se mostrasse eficaz em ambos. Portanto, reduçäo do peso corpóreo pareceu potencializar a açäo da pravastatina sendo recomendáveis estudos controlados para confirmar a hipótese

[Statins in hypercholesterolemia treatment]. / Estatinas no tratamento da hipercolesterolemia.

Statins are microorganism derived drugs that greatly impair the cell synthesis of cholesterol by competitively inhibiting the activity of the enzyme HMG-CoA reductase. Statins, however lower the blood level of cholesterol chiefly by increasing the number of high affinity receptors that recognize plasma LDL and by diminishing the VLDL synthesis rate in the liver. The latter explains the mild triglyceride reducing effect of these drugs. Statins efficiency in lowering the plasma cholesterol concentration is comparable to that of the bile acid binding polymers, but is better than that of the fibrates and nicotinic acid. Statins are better tolerated than the latter two drugs but are less efficient in lowering plasma triglycerides and in increasing the HDL-cholesterol concentrations. Tissue selectivity varies for the different statins but this is a secondary issue when the rarity of side effects is taken into account. Statins should be prescribed considering solely their pharmacologic efficiency and cost. Coronary angiography studies in coronary heart disease patients treated with placebo as compared to statins alone, or combined to other lipid lowering drugs, indicate that coronary artery disease regression can be achieved by pharmacological means.