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An organocatalytic cascade reaction of 2-nitrocyclohexanone and α, β-unsaturated aldehydes was developed. Bicyclo[3.3.1]nonanone products were obtained with good yields and excellent enantio- selectivities. The reaction occurred with unusual regioselectivity. A dienolate-iminium activation mechanism was proposed. The products were transformed to eight-membered cyclic ketones with high enantioselectivity. [ABSTRACT FROM AUTHOR]

The interview is with Zhen-Yu Chen, who is the associate editor of "Journal of Agricultural and Food Chemistry" and on the faculty of the Chinese University of Hong Kong. The topics include the responsibilities of the journal's associate editor, travel to institutes and universities in China to research journal publishing, and the outlook for agricultural research and international cooperation among researchers.

A number of 6-aryl-5,6-dihydrophenanthridines were prepared in good yields via an intramolecular dehydrogenative coupling of biaryl tertiary amines promoted by t-BuOK/DMF. A reaction mechanism involving a-aminoalkyl radical intermediates is suggested. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Effects of weight cycling on body composition" and A.M. Prentice and colleagues in a 1992 issue.

Abstract Background Trimethylamine-N-oxide (TMAO) is an independent risk factor for atherosclerosis. Consumption of hawthorn fruit is believed to be cardio-protective, yet whether it is able to suppress the TMAO-induced atherosclerosis remains unexplored. The present study was to investigate the effects of hawthorn fruit extract (HFE) on TMAO-exacerbated atherogenesis. Methods Five groups of male Apolipoprotein E knock-out (ApoE−/−) mice were fed a low-fat diet (LFD), a Western high-fat diet (WD), or one of the three WDs containing 0.2% TMAO (WD + TMAO), 0.2% TMAO plus 1% HFE (WD + TMAO + L-HFE), or 0.2% TMAO plus 2% HFE (WD + TMAO + H-HFE), respectively. After 12-weeks of intervention, plasma levels of TMAO, lipid profile, inflammatory biomarkers, and antioxidant enzyme activities were measured. Atherosclerotic lesions in the thoracic aorta and aortic sinus were evaluated. The sterols and fatty acids in the liver and feces were extracted and measured. Hepatic expressions of inflammatory biomarkers and antioxidant enzymes were analyzed. Results Dietary TMAO accelerated atherogenesis, exacerbated inflammation, and reduced antioxidant capacities in the plasma and the liver. TMAO promoted hepatic cholesterol accumulation by inhibiting fecal excretion of acidic sterols. HFE could dose-dependently reduce the TMAO-aggravated atherosclerosis and inflammation. HFE was also able to reverse the TMAO-induced reduction in antioxidant capacity by up-regulating the expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase 3 (GSH-Px3), and catalase (CAT) in the liver. Moreover, the hepatic cholesterol content was lowered by HFE via enhanced fecal excretion of neutral and acidic sterols. Conclusions The present results indicated that HFE was able to reduce the TMAO-exacerbated atherogenesis by attenuating inflammation and improving antioxidant capacity at least in mice. Graphic abstract

Trimethylamine-N-oxide (TMAO) has recently been identified as an independent risk factor for atherosclerosis. The present study was to investigate the effects of ginger extract (GE) on plasma cholesterol and inflammation in TMAO-exacerbated hypercholesterolemic mice. Forty-five mice were assigned into five groups and fed a non-cholesterol diet, a high-cholesterol diet, or one of the three experimental high-cholesterol diets containing 1% GE, 0.2% TMAO, or 0.2% TMAO plus 1% GE for 12 weeks. Results showed that dietary TMAO increased plasma total cholesterol (TC). GE decreased plasma TC in both non-TMAO-fed and TMAO-fed mice, by up-regulating the expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) and promoting fecal excretion of total acidic sterols. GE also lowered plasma levels of proinflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and monocyte chemotactic protein 1 (MCP-1). It was concluded that GE could alleviate the TMAO-aggravated elevation in plasma TC and vascular inflammation in high cholesterol diet-fed mice.

Piperine is the major pungent ingredient in black and white peppers. The present study investigated plasma cholesterol-lowering activity of piperine and associated underlying mechanism in hypercholesterolemia hamsters. Thirty-two hamsters were assigned into four groups receiving one of four diets namely a non-cholesterol diet (NCD), a high-cholesterol diet (HCD), and the two HCD diets containing 0.03% (PL) and 0.06% (PH) piperine, respectively, for 6 weeks. Results showed that PL and PH diets significantly reduced plasma total cholesterol (TC) by 16–17%, and non-high-density lipoprotein cholesterol (non-HDL-C) by 24–25%, respectively. This was accompanied by 84–109% increase in fecal excretion of neutral sterols with down-regulation on gene expression of intestinal Niemann-Pick C1-like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), and microsomal triacylglycerol transport protein (MTP). It was concluded that plasma TC-lowering activity of piperine was mediated by reducing the intestinal cholesterol absorption via inhibition on gene expression of intestinal NPC1L1, ACAT and MTP.

7S protein is one of four major storage proteins in soybean. The present study compared the relative cholesterol-lowering activity of the 7S protein with that of total soybean protein isolate (SPI). Forty-eight hamsters were divided into six groups fed non-cholesterol diet or one of five high-cholesterol diets containing 24.2% casein, 12.1–24.2% SPI, 12.1–24.2% 7S protein, respectively. Results showed the 7S protein reduced plasma total cholesterol (TC) by 20–41% while SPI reduced it by 9–16%. 7S protein increased the fecal excretion of neutral sterols by 43–116%, while SPI only had 18–68% increase. 7S protein increased the excretion of total bile acids by 208–367%, while SPI only increased it by 41–86%. 7S protein could not only down regulate gene expression of HMG-CoA reductase but also up regulate gene expression of CYP7A1. It was concluded that dietary 7S protein was more hypocholesterolemic than SPI, mediated by increasing the sterol excretion and decreasing the cholesterol synthesis.

β-Sitosterol (SI) is hypocholesterolemic. The present study investigated whether the blockage of its hydroxyl group would abolish its cholesterol-lowering activity. The blockage was made by methylating and ethylating the hydroxyl group on C3 position, leading to formation of β-sitosteryl 3β-methoxy (SM) and β-sitosteryl 3β-ethoxy (SE) derivatives. Male hamsters were divided into five groups (n = 8 each) and fed the non-cholesterol diet (NCD), high cholesterol diet containing 5 mmol of cholesterol (HCD), or one of the three high cholesterol experimental diets with addition of 5 mmol of SI (HCD + SI), 5 mmol of SM (HCD + SM) and 5 mmol of SE (HCD + SE), respectively, for 8 weeks. Results showed that SI could significantly reduce plasma total cholesterol (TC) by 17% (P

Docosahexaenoic acid (DHA) plays important roles in the prevention of ageing and ageing-related diseases. In this work, the anti-ageing effect of Schizochytrium mangrovei (SM), a marine microalga with high contents of DHA was investigated for the first time. In vitro results showed that SM enhanced the vitality of healthy pheochromocytoma (PC12) cells, whereas it had no protective effect under H2O2-induced oxidative stress. Meanwhile, SM exerted neuroprotective actions in vivo: the supplementation of SM significantly extended the lifespan of both wild type and SODn108 mutant flies Drosophila melanogaster, and ameliorated the age-related decline of locomotor function. This lifespan-extending activity was associated with the mRNA up-regulation of endogenous stress-defense genes such as CuZn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2), as well as the down-regulation of Methuselah (MTH) gene. Therefore, it was concluded that the anti-ageing capability of DHA-rich SM was mediated through the cooperation with endogenous stress-defense system rather than the direct interaction with oxidative free radicals.

Cholesterol is always an issue because blood total cholesterol (TC) and low-density lipoprotein (LDL) correlate strongly with coronary heart disease. Cholesterol homeostasis is maintained by a complex mechanism of sterol absorption, anabolism, catabolism and excretion. Nutraceuticals and functional foods which lower TC must affect the genes which regulate cholesterol homeostasis. In general, cholesterol-lowering functional foods and nutraceuticals can be classified into seven types namely intestinal Niemann-Pick C1 like 1 (NPC1L1) competitors, intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors, 3-hydroxy-3-methylglutaryl (HMG-CoA) reductase inhibitors, LDL receptor up-regulators, bile acid reabsorption inhibitors, cholesterol-7α-hydroxylase (CYP7A1) activators, and plasma cholesteryl ester transporting protein (CETP) inhibitors. This mini-review classifies the popular cholesterol-lowering nutraceuticals and functional foods, and explores their underlying mechanisms.

Cranberry is an excellent source of dietary antioxidants. The present study investigated the effect of cranberry anthocyanin (CrA) extract on the lifespan of fruit flies with focus on its interaction with aging-related genes including superoxide dismutase (SOD), catalase (CAT), methuselah (MTH), insulin receptor (InR), target of rapamycin (TOR), hemipterus (Hep), and phosphoenolpyruvate carboxykinase (PEPCK). Results showed that diet containing 20 mg/mL CrA could significantly prolong the mean lifespan of fruit flies by 10% compared with the control diet. This was accompanied by up-regulation of SOD1 and down-regulation of MTH, InR, TOR and PEPCK. The stress resistance test demonstrated that CrA could reduce the mortality rate induced by H2O2 but not by paraquat. It was therefore concluded that the lifespan-prolonging activity of CrA was most likely mediated by modulating the genes of SOD1, MTH, InR, TOR and PEPCK. [ABSTRACT FROM AUTHOR]

Palmitic acid, one of the saturated free fatty acids, impairs cardiovascular function as manifested by inducing vascular inflammation, apoptosis and over-production of reactive oxygen species (ROS) although the origin for ROS remains unclear. The present study investigated the cellular mechanisms underlying palmitate-induced impairment of endothelial function. Ex vivo treatment in tissue culture with palmitate concentration-dependently attenuated acetylcholine-induced endothelium-dependent relaxations, up-regulated the expression of cyclooxygenase-2 (COX-2) and elevated superoxide formation in mouse aortic endothelial cells (MAECs) measured by dihydroethidium (DHE) staining and electron paramagnetic resonance (EPR) spectroscopy. Superoxide scavengers, COX-2 inhibitor and thromboxane prostanoid (TP) receptor antagonist, but not COX-1 inhibitor reversed the harmful effects of palmitate. Furthermore, palmitate impaired acetylcholine-induced relaxations and raised superoxide in en face endothelium of aortas only from COX-1−/− mice but not from COX-2−/− mice. Palmitate increased the production and release of TXB2, a stable thromboxane A2 metabolite in mouse aortas, which was abolished by COX-2 inhibitor. Superoxide scavenger did not affect palmitate-induced up-regulated expression of COX-2 in MAECs. Both real time PCR and luciferase reporter gene assay confirmed COX-2 up-regulation in palmitate-treated MAECs and NF-κB was substantially involved in this up-regulation. The present study provides novel evidence that palmitate up-regulates COX-2 through NF-κB-dependent mechanism and resultant COX-2-associated oxidative stress impairs endothelium-dependent relaxations in mouse aortas. [ABSTRACT FROM AUTHOR]

It has been shown that dietary phytosterols intake is inversely related to plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations. The present study investigated effect of β-sitosterol intake frequency on plasma lipoprotein profile and the gene expression of transporters, receptors and enzymes involved in cholesterol metabolism. Thirty-three hamsters were divided into three groups with the control hamsters being gavage-administrated 3 mg cholesterol 3 times per day, whereas the second group being gavage-administered 3 mg β-sitosterol with 3 mg cholesterol 3 times per day (S-3) and the third group being gavage-administered 9 mg β-sitosterol with 3 mg cholesterol for one time and 3 mg cholesterol for the other two times per day (S-1). Results demonstrated that compared with the control group, hamsters gavage-fed β-sitosterol had a significant decrease in plasma TC and non-high density lipoprotein cholesterol (Non- HDL-C) concentration, but there was no significant difference between S-3 and S-1 groups. Real time PCR analysis revealed that the cholesterol-lowering activity of β-sitosterol was mediated by its inhibition on the intestinal cholesterol absorption with up- regulation of Niemann-Pick C1 like 1 (NPC1L1), ATP binding cassette transporters 5 and 8 (ABCG5/8) and microsomal triacylglycerol transport protein (MTP), but no significant difference was found between S-3 and S-1 groups. It was concluded that β-sitosterol was effective in reducing plasma cholesterol level and for a given dose of β-sitosterol, the administration frequency had no effect on plasma lipoprotein profiles. [ABSTRACT FROM AUTHOR]

Cilnidipine is a dual blocker of L-type voltage-gated Ca2+ channels in vascular smooth muscle and N-type Ca2+ channels in sympathetic nerve terminals that supply blood vessels. However, the clinical benefits of cilnidipine and underlying mechanisms are incompletely understood. This study was designed to compare the time course of relaxant responses to cilnidipine and nifedipine, and to examine the role of endothelial NO and [Ca2+]i in the vasorelaxation.Porcine left circumflex coronary arteries were isolated and isometric tension was measured with Grass force transducers. Endothelial [Ca2+]i in intact arteries was determined by a calcium fluorescence imaging technique. The free radical scavenging capacity was also assayed.Cilnidipine and nifedipine induced concentration-dependent relaxations in high KCl-precontracted artery rings, while the former-induced relaxation was slower as compared to the latter. Treatment with L-NAME or ODQ reduced relaxations to cilnidipine or nifedipine to the same extent as in rings without endothelium. Indomethacin or ω-conotoxin had no effects. L-Arginine antagonized the effect of L-NAME on cilnidipine-induced relaxations. Cilnidipine did not affect sodium nitroprusside-induced relaxation in rings with and without endothelium.Cilnidipine and nifedipine caused extracellular Ca2+-dependent increases in endothelial [Ca2+]i in intact arteries and cilnidipine's action had a slower onset, similar to that of cilnidipine-induced relaxation.Neither cilnidipine nor nifedipine exhibited a free radical scavenging property.The present results demonstrate that cilnidipine can produce endothelium-dependent relaxation in porcine coronary arteries in vitro in addition to blocking Ca2+ channels. Like short-acting nifedipine, cilnidipine-dependent relaxation, albeit to a slower onset, is partly mediated by endothelial NO but not by prostacyclin. The increased release or bioavailability of NO may causally result from elevated endothelial [Ca2+]i in arteries. The Ca2+ channel-independent effect suggests the usefulness of cilnidipine in the treatment of cardiovascular diseases associated with diminished NO release, such as atherosclerosis.British Journal of Pharmacology (2006) 147, 55–63. doi:10.1038/sj.bjp.0706450; published online 21 November 2005 [ABSTRACT FROM AUTHOR]