Characteristic fingerprinting based on macamides for discrimination of maca (Lepidium meyenii) by LC/MS/MS and multivariate statistical analysis.

BACKGROUND: Macamides with a benzylalkylamide nucleus are characteristic and major bioactive compounds in the functional food maca (Lepidium meyenii Walp). The aim of this study was to explore variations in macamide content among maca from China and Peru. Twenty-seven batches of maca hypocotyls with different phenotypes, sampled from different geographical origins, were extracted and profiled by liquid chromatography with ultraviolet detection/tandem mass spectrometry (LC-UV/MS/MS). RESULTS: Twelve macamides were identified by MS operated in multiple scanning modes. Similarity analysis showed that maca samples differed significantly in their macamide fingerprinting. Partial least squares discriminant analysis (PLS-DA) was used to differentiate samples according to their geographical origin and to identify the most relevant variables in the classification model. The prediction accuracy for raw maca was 91% and five macamides were selected and considered as chemical markers for sample classification. CONCLUSION: When combined with a PLS-DA model, characteristic fingerprinting based on macamides could be recommended for labelling for the authentication of maca from different geographical origins. The results provided potential evidence for the relationships between environmental or other factors and distribution of macamides. © 2016 Society of Chemical Industry.

The expression of efflux and uptake transporters are regulated by statins in Caco-2 and HepG2 cells.

AIM: Statin disposition and response are greatly determined by the activities of drug metabolizing enzymes and efflux/ uptake transporters. There is little information on the regulation of these proteins in human cells after statin therapy. In this study, the effects of atorvastatin and simvastatin on mRNA expression of efflux (ABCB1, ABCG2 and ABCC2) and uptake (SLCO1B1, SLCO2B1 and SLC22A1) drug transporters in Caco-2 and HepG2 cells were investigated. METHODS: Quantitative real-time PCR was used to measure mRNA levels after exposure of HepG2 and Caco-2 cells to statins. RESULTS: Differences in mRNA basal levels of the transporters were as follows: ABCC2>ABCG2>ABCB1>SLCO1B1>>>SLC22A1>SLC O2B1 for HepG2 cells, and SLCO2B1>>ABCC2>ABCB1>ABCG2>>>SLC22A1 for Caco-2 cells. While for HepG2 cells, ABCC2, ABCG2 and SLCO2B1 mRNA levels were significantly up-regulated at 1, 10 and 20 micromol/L after 12 or 24 h treatment, in Caco-2 cells, only the efflux transporter ABCB1 was significantly down-regulated by two-fold following a 12 h treatment with atorvastatin. Interestingly, whereas treatment with simvastatin had no effect on mRNA levels of the transporters in HepG2 cells, in Caco-2 cells the statin significantly down-regulated ABCB1, ABCC2, SLC22A1, and SLCO2B1 mRNA levels after 12 or 24 h treatment. CONCLUSION: These findings reveal that statins exhibits differential effects on mRNA expression of drug transporters, and this effect depends on the cell type. Furthermore, alterations in the expression levels of drug transporters in the liver and/or intestine may contribute to the variability in oral disposition of statins.Acta Pharmacologica Sinica (2009) 30: 956-964; doi: 10.1038/aps.2009.85; published online 22 June 2009.

Vascular and metabolic response to statin in the mildly hypertensive hypercholesterolemic elderly.

INTRODUCTION: Much evidence indicates the importance of the endothelium and hypercholesterolemia in atherosclerosis, as well as the decline in endothelial function with aging. However, it is unclear if treating dyslipidemia in elderly patients improves endothelial function and reduces C-reactive protein levels. OBJECTIVES: To evaluate vasomotor function, lipids and C-reactive protein in mildly hypertensive and hypercholesterolemic elderly patients treated with atorvastatin. METHODS: Forty-seven elderly Brazilian subjects (> or = 65 years old) with LDL cholesterol (LDL-c) > or = 130 mg/dL were randomly assigned, in a double-blinded manner, to receive either placebo (n = 23) or 20 mg/day of atorvastatin (n = 24) for 4 weeks. Exclusion criteria included diabetes, serious hypertension, obesity, steroid use, hormone replacement, and statin use within the previous six months. All patients underwent clinical examinations, laboratory tests (glucose, lipids, liver enzymes, creatine phosphokinase and high sensitivity C-reactive protein) and assessment of vasomotor function by high-resolution ultrasound examination of the brachial artery (flow-mediated dilation and sublingual nitrate), both before and after treatment. RESULTS: The patients were 65 to 91 years old; there was no significant difference between basal flow-mediated dilation of placebo (7.3 +/- 6.1%) and atorvastatin (4.5 +/- 5.1%; p = 0.20). The same was observed after treatment (6.6 +/- 6.2 vs. 5.0 +/- 5.6; p = 0.55). The initial nitrate dilatation (8.1 +/- 5.4% vs. 10.8 +/- 7.5%; p = 0.24) and that after 4 week treatment (7.1 +/- 4.7% vs. 8.6 +/- 5.0%; p = 0.37) were similar. Atorvastatin produced a reduction of 20% of the C-reactive protein and 42% in the LDL-c; however, there were no changes in the flow-mediated dilation. CONCLUSIONS: Atorvastatin produced a significant change of lipids and C-reactive protein; however, there were no changes in vasomotor function, suggesting the existence of intrinsic age-related vessel alterations.

Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats.

The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.

Vascular and metabolic response to statin in the mildly hypertensive hypercholesterolemic elderly

INTRODUCTION: Much evidence indicates the importance of the endothelium and hypercholesterolemia in atherosclerosis, as well as the decline in endothelial function with aging. However, it is unclear if treating dyslipidemia in elderly patients improves endothelial function and reduces C-reactive protein levels. OBJECTIVES: To evaluate vasomotor function, lipids and C-reactive protein in mildly hypertensive and hypercholesterolemic elderly patients treated with atorvastatin. METHODS: Forty-seven elderly Brazilian subjects (> 65 years old) with LDL cholesterol (LDL-c) > 130 mg/dL were randomly assigned, in a double-blinded manner, to receive either placebo (n = 23) or 20 mg/day of atorvastatin (n = 24) for 4 weeks. Exclusion criteria included diabetes, serious hypertension, obesity, steroid use, hormone replacement, and statin use within the previous six months. All patients underwent clinical examinations, laboratory tests (glucose, lipids, liver enzymes, creatine phosphokinase and high sensitivity C-reactive protein) and assessment of vasomotor function by high-resolution ultrasound examination of the brachial artery (flow-mediated dilation and sublingual nitrate), both before and after treatment. RESULTS: The patients were 65 to 91 years old; there was no significant difference between basal flow-mediated dilation of placebo (7.3 ± 6.1 percent) and atorvastatin (4.5 ± 5.1 percent; p = 0.20). The same was observed after treatment (6.6 ± 6.2 vs. 5.0 ± 5.6; p = 0.55). The initial nitrate dilatation (8.1 ± 5.4 percent vs. 10.8 ± 7.5 percent; p = 0.24) and that after 4 week treatment (7.1 ± 4.7 percent vs. 8.6 ± 5.0 percent; p = 0.37) were similar. Atorvastatin produced a reduction of 20 percent of the C-reactive protein and 42 percent in the LDL-c; however, there were no changes in the flow-mediated dilation. CONCLUSIONS: Atorvastatin produced a significant change of lipids and C-reactive protein; however, there were no changes in vasomotor ...

Combinação de fármacos na abordagem das dislipidemias: associação entre estatinas e niacina / Combination of drugs: statins and niacin

A combinação de estatinas com niacina se apresenta como uma atraente associação, na presença de dislipidemia mista com níveis de HDL baixo, quando monoterapia é insuficiente para o alcance das metas lipídicas. Benefícios clínicos foram observados com a combinação de estatinas com niacina nos estudos FATS, HATS e ARBITER 2, mostrando atenuação no desenvolvimento da aterosclerose e/ou redução de eventos coronários, acompanhados de alterações lipídicas favoráveis. Em geral, esta combinação é bem tolerada. Recomenda-se monitoração adequada das enzimas hepáticas e muscular e, ainda, titulação cuidadosa de cada uma das drogas combinadas.

[Drug combinations: statins and niacin]. / Combinação de fármacos na abordagem das dislipidemias: associação entre estatinas e niacina.

Combination of statins with niacin appears to be an attractive association, in the presence of mixed dyslipidemia with low HDL-c levels, when monotherapy is insufficient to achieve target lipid levels. Clinical benefits were observed by the combination of statins with niacin in the FATS, HATS and ARBITER 2 trials, showing attenuation of atherosclerosis development and/or reduction in coronary events following favorable lipid changes. In general, this combination can be well-tolerated. Recommendations for appropriate monitoring of liver and muscle enzymes are important to reduce the rate of side effects. In addition, careful titration of each drug is recommended.