Jingnan Chen

Biology of Ageing and Role of Dietary Antioxidants

Interest in relationship between diet and ageing is growing. Research has shown that dietary calorie restriction and some antioxidants extend lifespan in various ageing models. On the one hand, oxygen is essential to aerobic organisms because it is a final electron acceptor in mitochondria. On the other hand, oxygen is harmful because it can continuously generate reactive oxygen species (ROS), which are believed to be the factors causing ageing of an organism. To remove these ROS in cells, aerobic organisms possess an antioxidant defense system which consists of a series of enzymes, namely, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). In addition, dietary antioxidants including ascorbic acid, vitamin A, vitamin C, α-tocopherol, and plant flavonoids are also able to scavenge ROS in cells and therefore theoretically can extend the lifespan of organisms. In this connection, various antioxidants including tea catechins, theaflavins, apple polyphenols, black rice anthocyanins, and blueberry polyphenols have been shown to be capable of extending the lifespan of fruit flies. The purpose of this review is to brief the literature on modern biological theories of ageing and role of dietary antioxidants in ageing as well as underlying mechanisms by which antioxidants can prolong the lifespan with focus on fruit flies as an model.

DPA n-3, DPA n-6 and DHA improve lipoprotein profiles and aortic function in hamsters fed a high cholesterol diet

The present study examined the cholesterol-lowering activity of omega-3 docosapentaenoic acid (DPA n-3), omega-6 docosapentaenoic acid (DPA n-6) and docosahexaenoic acid (DHA), and their interaction with gene expression of transporters, receptors and enzymes involved in cholesterol absorption and metabolism as well as their effect on aortic function. Forty hamsters were fed either the control diet containing 0.4% stearic acid or one of the three experimental diets containing 0.4% DPA n-3, 0.4% DPA n-6 and 0.4% DHA. Results showed that supplementation of these three fatty acids reduced plasma total cholesterol (TC) and non high-density-lipoprotein cholesterol (non-HDL-C) by 29-33% and 29-50%, respectively, compared with the control. The reduction in TC and non-HDL-C was accompanied by down-regulation of hepatic SREBP-2 and HMG-CoA reductase. Aorta from DPA n-3 and DHA groups was found to have significantly lesser tension and relax better than that from the control and DPA n-6 hamsters, largely mediated by their inhibition on the gene expression of cycloxygense-2 (COX-2). It was concluded that all three fatty acids were beneficial in improving lipoprotein profile with DPA n-3 and DHA having better effect on aortic function.

Oxidative stability of conjugated linolenic acids.

Interest in conjugated linolenic acid (CLnA) and conjugated linoleic acid (CLA) as functional lipids is growing. The present study was (i) to study the oxidative stability of individual CLnA isomers and (ii) to compare the oxidative stabilities of CLnA and CLA with their corresponding nonconjugated counterparts, α-linolenic acid (LN) and linoleic acid (LA). The oxidation was carried out in air at 50 °C and monitored by the gas-liquid chromatography (GC) and the oxygen consumption test. First, it was found that CLnA was most unstable followed by CLA, LN, and LA in decreasing order. Second, analyses of silver ion high-performance liquid chromatography (Ag(+)-HPLC) demonstrated that t,t,t-CLnA isomers had greater stability than c,t,t-CLnA and c,t,c-CLnA isomers. Finally, both green tea catechins (GTCs) and butylated hydroxytoluene (BHT) were capable of preventing the CLnA oxidation, with the former being more effective than the latter.

Microalga decreases plasma cholesterol by down-regulation of intestinal NPC1L1, hepatic LDL receptor, and HMG-CoA reductase.

The present study examined the cholesterol-lowering activity of algal powder (AP), algal lipids (AL), and algal residue (AR) and their interaction with genes of transporters, receptors, and enzymes involved in cholesterol absorption and metabolism. In this experiment, 48 hamsters were fed either control diet or one of the three experimental diets containing 2% AP, 1.0% AL, or 1.0% AR for 6 weeks. Plasma total cholesterol (TC) and non-high-density-lipoprotein-cholesterol (non-HDL-C) were significantly decreased in the AP and AL groups but not in the AR group compared with those in the control hamsters. It was found that the cholesterol-lowering activity of AP and AL was associated with down-regulation of hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, low-density lipoprotein receptor (LDLR), and intestinal Niemann-Pick C1-like 1 (NPC1L1) transporter. It was concluded that the alga possessed the cholesterol-lowering activity and its lipids were the active ingredients. The mechanisms underlying the cholesterol-lowering activity of algae were mediated most likely by increasing the sterol excretion and decreasing the cholesterol absorption and synthesis.

Cholesterol-lowering activity of sesamin is associated with down-regulation on genes of sterol transporters involved in cholesterol absorption.

Sesame seed is rich in sesamin. The present study was to (i) investigate the plasma cholesterol-lowering activity of dietary sesamin and (ii) examine the interaction of dietary sesamin with the gene expression of sterol transporters, enzymes, receptors, and proteins involved in cholesterol metabolism. Thirty hamsters were divided into three groups fed the control diet (CON) or one of two experimental diets containing 0.2% (SL) and 0.5% (SH) sesamin, respectively, for 6 weeks. Plasma total cholesterol (TC) levels in hamsters given the CON, SL, and SH diets were 6.62 ± 0.40, 5.32 ± 0.40, and 5.00 ± 0.44 mmol/L, respectively, indicating dietary sesamin could reduce plasma TC in a dose-dependent manner. Similarly, the excretion of total fecal neutral sterols was dose-dependently increased with the amounts of sesamin in diets (CON, 2.65 ± 0.57; SL, 4.30 ± 0.65; and SH, 5.84 ± 1.27 μmol/day). Addition of sesamin into diets was associated with down-regulation of mRNA of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporters subfamily G members 5 and 8 (ABCG5 and ABCG8). Results also showed that dietary sesamin could up-regulate hepatic cholesterol-7α-hydroxylase (CYP7A1), whereas it down-regulated hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and liver X receptor alpha (LXRα). It was concluded that the cholesterol-lowering activity of sesamin was mediated by promoting the fecal excretion of sterols and modulating the genes involved in cholesterol absorption and metabolism.

Algal sterols are as effective as β-sitosterol in reducing plasma cholesterol concentration.

The present study examined the cholesterol-lowering activity of sterol extract (SE) derived from alga Schizochytrium sp. and its interaction with gene expression of transporters, receptors, and enzymes involved in cholesterol absorption and metabolism. GC-MS analyses found that SE was a mixture of various sterols including lathosterol, ergosterol, stigmasterol, 24-ethylcholesta-5,7,22-trienol, stigmasta-7,24(24(1))-dien-3β-ol, and cholesterol. Results showed that SE at doses of 0.06 and 0.30 g/kg diet were able to decrease plasma cholesterol concentration by 19.5 and 34%, respectively, compared with the control, in hamsters maintained on a 0.1% high-cholesterol diet. SE at a dose of 0.30 g/kg diet was as effective as β-sitosterol in reducing plasma total cholesterol (TC). SE-induced reduction in plasma TC was accompanied by down-regulation of intestinal acyl-CoA:cholesterol acyltransferase 2 (ACAT2) and hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and up-regulation of hepatic low-density lipoprotein (LDL) receptor. Addition of SE to the diet increased the excretion of total fecal sterols. It was concluded that SE possessed the same cholesterol-lowering activity as β-sitosterol and the underlying mechanisms were mediated by increasing sterol excretion and decreasing cholesterol absorption and synthesis.

Differential incorporation of dietary conjugated linolenic and linoleic acids into milk lipids and liver phospholipids in lactating and suckling rats

Interest in health benefits of conjugated fatty acids is growing. The present study compared the incorporation pattern of dietary conjugated linolenic acids (CLnA) into milk with that of conjugated linoleic acids (CLA). Lactating Sprague-Dawley rats (Day 1) were divided into five groups fed the control diet (n=4) or one of four experimental diets supplemented with 1-2% CLA or CLnA mixture (n=8 each). Supplementation of 1% and 2% CLA led to enrichment of 4.17% and 8.57% CLA, respectively, while supplementation of 1% and 2% CLnA resulted in enrichment of only 0.98% and 1.71% CLnA in the milk lipids, demonstrating the transfer of CLnA from maternal diet to milk was discriminated. When the lactating rats were given a diet containing a CLnA mixture of 9t,11t,13t-, 9c,11t,13t- and 9c,11t,13c-CLnA isomers, two CLA isomers, namely, 9t,11t (0.59-0.90%) and 9c,11t (1.21-1.96%), were found in the milk, suggesting that three CLnA isomers were Delta-13 saturated. Dietary CLnA at 1-2% had no effect on liver phospholipid (PL) fatty acid composition of both maternal and suckling rats, whereas dietary CLA increased docosahexaenoic acid (4c,7c,10c,13c,16c,19c-22:6) and palmitic acid (16:0) proportionally in the PL of maternal rats, but it suppressed 16:0 in the PL of suckling rats. It is concluded that maternal rats incorporate CLnA isomers into milk differently from that of CLA isomers. Most interesting is that maternal rats can metabolically convert CLnA to CLA.

Cynarin-Rich Sunflower (Helianthus annuus) Sprouts Possess Both Antiglycative and Antioxidant Activities

The present study examined the antiglycative and antioxidant properties of four edible sprouts popular in Chinese markets. In a protein-reducing sugar model, the sunflower sprout Helianthus annuus exhibited the strongest inhibitory effects against the formation of advanced glycation end products (AGEs). At a concentration of 1.0 mg/mL, its inhibitory rate achieved 83.29%, which is stronger than that of aminoguanidine (1 mM), a well-known synthetic antiglycative agent (with an inhibitory rate of 80.88%). The antioxidant capacity of H. annuus was also much stronger than other sprout samples in terms of free radical scavenging and reducing properties. An active ingredient contributing to the observed activities was identified as cynarin (1,5-dicaffeoylquinic acid). This is the first report of the novel function of cynarin to intervene against glycoxidation. Given the key roles of AGEs and oxidation in the pathogenesis of diabetes, the sunflower sprout H. annuus rich in cynarin may be regarded as a beneficial food choice for diabetic patients.

Cholesteryl Ester Species Differently Elevate Plasma Cholesterol in Hamsters

This study was to examine the effect of free cholesterol (C) and individual cholesteryl ester (CE) species, namely cholesteryl palmitate (CP), cholesteryl stearate (CS), cholesteryl oleate (CO), and cholesteryl linoleate (CL) on plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triacylglycerols (TG) in hamsters. Results showed that addition of dietary CE species into diet at 0.1% differently raised plasma TC concentrations, with CO elevating plasma TC to 331 mg/dL, while CS raised plasma TC only to 220 mg/dL. It was found that CS was a poor substrate of pancreatic cholesterol esterase, while CO was a good substrate. The fecal analysis showed CS-fed hamsters had the highest fecal cholesterol concentration, while RT-PCR analysis found CS feeding was associated with down-regulations of intestinal Niemann-Pick C1 like 1 (NPC1L1) and acyl-CoA: cholesterol acyltransferase 2 (ACAT2) as well as microsomal triacylglycerol transport protein (MTP). It was therefore concluded that the plasma cholesterol-raising activity of CE species was partially governed by their hydrolysis rates in the intestine, and the relative low raising activity associated with CS was mediated by down-regulation of intestinal NPC1L1, ACAT2, and MTP.

Cranberry anthocyanin as an herbal medicine lowers plasma cholesterol by increasing excretion of fecal sterols

BACKGROUND Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. HYPOTHESIS The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion. METHODS Forty-four hamsters were randomly divided into five groups and fed one of the five diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD), a HCD diet supplemented with a low dose of 1% CrA (CL), a HCD diet supplemented with a high dose of 2% CrA (CH), and a HCD diet supplemented with 0.5% cholestyramine as a positive control drug (P-CTL), respectively, for six weeks. Plasma lipoprotein cholesterol was quantified using the enzymatic kits, while the gene expressions of transporters, enzymes and receptors involved in cholesterol absorption and metabolism were quantified using the quantitative RT-PCR. Fecal sterols were quantified using gas chromatography (GC). RESULTS Plasma total cholesterol and aorta atherosclerotic plaque decreased dose-dependently with the increasing amounts of CrA added into diets. This was accompanied by a dose-dependent increase in excretion of both neutral and acidic sterols. CrA had no effect on the mRNA levels of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl CoA:cholesterol acyltransferase2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5) as well as hepatic cholesterol-7α-hydroxylase (CYP7A1), 3-Hydroxy-3-methylglutaryl reductase (HMG-CoA-R), sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDL-R), and Liver X receptor alpha (LXRα). CONCLUSION CrA as an herbal medicine could favorably modify the lipoprotein profile in hamsters fed a high cholesterol diet by enhancing excretion of fecal neutral and acidic sterols, most likely not mediated by interaction with genes of transporters, enzymes and proteins involved in cholesterol absorption and metabolism.