The effect of single dietary fibre (DF) on lowering uric acid (UA) level has been reported in the literature. However, the potential protective mechanism of DF against potassium oxybate-induced hyperuricaemia (HUA), as modelled by prophylactic administration, remains unclear. The data demonstrate that DF significantly decreased serum and cerebral tissue UA concentrations, inhibited xanthine oxidase expression and activity in the liver and reduced levels of creatinine and urea nitrogen in the serum. Additionally, it mitigated the deposition of amyloid-β in cerebral tissue. Correlation analysis showed that DF modulated the Toll-like receptor 4/NF-κB signalling pathway, attenuating oxidative stress and inflammatory responses in HUA mice. Additionally, DF helps to maintain the composition of the gut microbiota, reducing harmful Desulfovibrio and enriching beneficial Akkermansia and Ruminococcus populations. The results of the faecal metabolomics analysis indicate that DF facilitates the regulation of metabolic pathways involved in oxidative stress and inflammation. These pathways include pyrimidine metabolism, tryptophan metabolism, nucleotide metabolism and vitamin B6 metabolism. Additionally, the study found that DF has a preventive effect on anxiety-like behaviour induced by HUA. In summary, DF shows promise in mitigating HUA and cognitive deficits, primarily by modulating gut microbiota and metabolites.

Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

The present study evaluated the antihypertrophic potential of the ethanolic extract of Boerhaavia diffusa (BDE), a well-known edible cardiotonic plant reported in Ayurveda against angiotensin II-induced hypertrophy in H9c2 cardiac myoblast cells. Markers of hypertrophy such as cell size, protein content and the concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were analysed for the confirmation of hypertrophy induction. Angiotensin II (100 nm) caused an increase in cell volume (69·26 (sd 1·21) %), protein content (48·48 (sd 1·64) %), ANP (81·90 (sd 1·22) %) and BNP (108·57 (sd 1·47) %). BDE treatment significantly reduced cell volume, protein content and the concentrations of ANP and BNP (P≤ 0·05) in H9c2 cells. The activity of various antioxidant enzymes and the concentration of reduced glutathione, which was lowered due to hypertrophy, were increased in BDE-treated cells. The BDE treatment also reduced intracellular reactive oxygen species generation, lipid peroxidation and protein carbonyls in cells. In addition, the expression patterns of NF-κβ and transforming growth factor β1 were found to be increased during hypertrophy, and their expressions were reduced on BDE treatment. In vitro chemical assays showed that BDE inhibits angiotensin-converting enzyme and xanthine oxidase in a dose-dependent manner with an estimated 50 % effective concentration (EC50) value of 166·12 (sd 2·42) and 60·05 (sd 1·54) μg/ml, respectively. The overall results clearly indicate the therapeutic potential of B. diffusa against cardiac hypertrophy, in addition to its nutritional qualities.

The present study was to investigate the effects of l-arginine (l-Arg) supplementation on cardiac oxidative stress and the inflammatory response in rats following acute exhaustive exercise on a treadmill. Rats were randomly divided into four groups: sedentary control (SC); SC with l-Arg treatment (SC+Arg); exhaustive exercise (E); exhaustive exercise with l-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% l-Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a treadmill at a final speed of 30m/min, 10% grade, at approximately 70–75% VO2max. The results showed a significant increase in cardiac xanthine oxidase (XO) and myeloperoxidase activities and membrane lipid peroxidation endproduct (malondialdehyde; MDA) levels of exercised rats compared with SC rats. The increased cardiac XO activity and MDA levels in exercised rats were significantly decreased in exercised rats supplemented with l-Arg. Myocardial GSSG content increased whereas the GSH:GSSG ratio was depressed in exercised rats compared with SC rats. Cardiac GSSG levels significantly decreased, whereas total glutathione, GSH and the GSH:GSSG ratio increased in exercised rats supplemented with l-Arg compared with exercised rats. The activities of creatinine kinase (CK) and lactate dehydrogenase (LDH), and lactate, uric acid, and nitrite and nitrate levels in the plasma significantly increased in exercised rats compared with SC rats. The activities of plasma CK and LDH were significantly decreased in l-Arg-supplemented plus exercised rats compared with exercised rats. These findings suggest that l-Arg supplementation reduces the oxidative damage and inflammatory response on the myocardium caused by exhaustive exercise in rats.

Strenuous exercise is known to induce oxidative stress leading to the generation of free radicals. The purpose of the present study was to investigate the effects of lycopene, an antioxidant nutrient, at a relatively low dose (2·6 mg/kg per d) and a relatively high dose (7·8 mg/kg per d) on the antioxidant status of blood and skeletal muscle tissues in rats after exhaustive exercise. Rats were divided into six groups: sedentary control (C); sedentary control with low-dose lycopene (CLL); sedentary control with high-dose lycopene (CHL); exhaustive exercise (E); exhaustive exercise with low-dose lycopene (ELL); exhaustive exercise with high-dose lycopene (EHL). After 30 d, the rats in the three C groups were killed without exercise, but the rats in the three E groups were killed immediately after an exhaustive running test on a motorised treadmill. The results showed that xanthine oxidase (XO) activities of plasma and muscle, and muscular myeloperoxidase (MPO) activity in group E were significantly increased compared with group C. Compared with group E, the elevations of XO and MPO activities of muscle were significantly decreased in group EHL. The malondialdehyde concentrations of plasma and tissues in group E were significantly increased by 72 and 114 %, respectively, compared with those in group C. However, this phenomenon was prevented in rats of the ELL and EHL groups. There was no significant difference in the GSH concentrations of erythrocytes in each group; however, exhaustive exercise resulted in a significant decrease in the GSH content of muscle. In conclusion, these results suggested that lycopene protected muscle tissue from oxidative stress after exhaustive exercise.

Four experiments were performed to study the kinetics of purine metabolism and urinary excretion in Zebu crossbred cattle. Fasting excretion was established in Expt 1, using eighteen male Bos indicus×Bos taurus crossbred cattle (261 (se 9·1) kg body weight), six of each of the following genotypes: 5/8 Bos indicus, 1/2 Bos indicus and 3/8 Bos indicus. No significant differences were observed among genotypes in fasting purine derivative excretion (277·3 (se 35·43) μmol/metabolic body weight). In a second experiment we measured the xanthine oxidase activity, which was higher in liver than in duodenal mucosa (0·64 and 0·06 (se 0·12) units/g wet tissue per min respectively; P>0·05) being in plasma 0·60 (se 0·36) units/l per min. The kinetics of uric acid were measured by intravenous pulse dose of [1,3-15N]uric acid (Expt 3). The cumulative recovery of the isotope in urine was 82 (se 6·69) %, and uric acid plasma removal, pool size and mean retention time were 0·284 (se 0·051) per h, 5·45 (se 0·823) mmol and 3·52 (se 0·521) h, respectively. Allantoin was removed from plasma at an estimated fractional rate of 0·273 (se 0·081) per h and mean retention was 3·66 (se 1·08) h. In Expt 4, the relationship between urinary purine derivative excretion (Y; mmol/d) and digestible organic matter intake (X, kg/d) was defined by the equation: Y=7·69 (se 4·2)+5·69 (se 1·68) X; n 16, Se 1·31, r 0·67.

Five experiments were carried out to extend knowledge of purine metabolism in the camel (Camelus dromedarius) and to establish a model to enable microbial protein outflow from the forestomachs to be estimated from the urinary excretion of purine derivatives (PD; i.e. xanthine, hypoxanthine, uric acid, allantoin). In experiment 1, four camels were fasted for five consecutive days to enable endogenous PD excretion in urine to be determined. Total PD excretion decreased during the fasting period to 267 (se 41·5)?μmol/kg body weight (W)0·75 per d. Allantoin and xanthine+hypoxanthine were consistently 86 and 6·1?% of total urinary PD during this period but uric acid increased from 3·6?% to 7·4?%. Xanthine oxidase activity in tissues (experiment 2) was (μmol/min per g fresh tissue) 0·038 in liver and 0·005 in gut mucosa but was not detected in plasma. In experiment 3, the duodenal supply of yeast containing exogenous purines produced a linear increase in urinary PD excretion rate with the slope indicating that 0·63 was excreted in urine. After taking account of endogenous PD excretion, the relationship can be used to predict purine outflow from the rumen. From the latter prediction, and also the purine:protein ratio in bacteria determined in experiment 5, we predicted the net microbial outflow from the rumen. In experiment 4, with increasing food intake, the rate of PD excretion in the urine increased linearly by about 11·1?mmol PD/kg digestible organic matter intake (DOMI), equivalent to 95?g microbial protein/kg DOMI.

Xanthine oxidoreductase (XOR) was purified from goats' milk. The u.v.–visible absorption spectrum was essentially identical to those of the corresponding bovine and human milk enzymes and showed an A280/A450 ratio of 5·20±0·12, indicating a high degree of purity. Like bovine and human milk XORs, enzyme purified from goats' milk showed a single band on SDS-PAGE corresponding to a subunit with approximate Mr 150000. On Western blotting, mouse monoclonal anti-human XOR antibody cross-reacted with purified caprine and bovine XORs. The specific xanthine oxidase activity of goats' milk XOR, however, was very much lower than that of bovine XOR, although NADH oxidase activities of XOR from the two sources were similar. In these respects, the caprine milk XOR mirrors the human milk enzyme, in which case the kinetic effects have previously been attributed to relatively low molybdenum content. The molybdenum content of goats' milk XOR also was shown to be relatively low, with 0·09 atoms Mo per subunit, compared with 0·55 atoms Mo per subunit for the bovine enzyme. A parallel purification of human milk XOR showed 0·03 atoms Mo per subunit. The possible physiological significance of the low molybdenum content of the caprine milk enzyme and of its correspondingly low enzymic activity is discussed.

Three experiments were carried out to establish a response model between intake and urinary excretion of purine compounds. In Expt 1 the relationship between the intake of purine bases (PB) and the excretion of total purine derivatives (PD) was determined in seven growing rabbits with a mean initial live weight (LW) of 2·03 (SE 0·185) kg, aged 70 d, each fitted with a wooden neck collar to prevent caecotrophagy. They were fed on five experimental diets formulated with different levels of nucleic acids (0·00, 3·75, 7·50, 11·25, 15·00 g yeast-RNA/kg diet). The relationship between intake of purine (x, μmol/kg W0·75) and total urinary PD excretion (y, μmol/kg W0·75), y = 0·56 + 0·67x (r2 0·86; RSD 0·338), indicated that about 70% of duodenal PB were recovered as urinary PD and that the endogenous contribution was constant and independent of dietary PB supply. Endogenous excretion of PD (allantoin and uric acid) was measured in a second experiment using six rabbits fed on a purine-free diet and fitted with neck collars to avoid caecotrophagy. Basal daily urinary excretion values for allantoin and uric acid were 532 (SE 33·9) and 55 (SE 7·3) μmol/kg W0·75 respectively; xanthine and hypoxanthine were not found in urine samples and therefore the sum of allantoin and uric acid should comprise the total excretion of PD (588 (SE 40·1) μmol/kg W0·75). The xanthine oxidase (EC 1·2.3·2) activity in plasma, liver, duodenum, jejunum and kidney was measured in a third experiment. The activities of xanthine oxidase in duodenal and jejunal mucosa, liver and kidney were: 0·61 (SE 0·095), 0·37 (SE 0·045), 0·035 (SE 0·001) and 0 units/g fresh tissue respectively and in plasma 2·96 (SE 0·094) units/1. The results show that urinary excretion of PD may be a useful tool to estimate duodenal PB input and microbial protein intake once the relationship between PB and N has been established in caecal micro-organisms.

The urinary excretion of purine derivatives (PD) was measured in six buffaloes (Bubalis bubalis) during fasting and in fourteen buffaloes given four restricted levels of roughage (2·5-4·8 kg DM/d). Only allantoin and uric acid, not xanthine and hypoxanthine, were present in the urine, the pattern of excretion being similar to that in cattle. The fasting PD excretion amounted to 0·20 (SD 0·06) mmol/kg metabolic weight (W0·75) per d, and the rate of PD excretion as a linear function of feed intake was 5·2 mmol/kg digestible organic matter intake. Both values were considerably lower than the values for cattle reported in the literature. Creatinine excretion values were 0·33 (SD 0·06) and 0·44 (SD 0·09) mmol/kg W0.75 per d determined in fasting and feeding periods respectively. Fasting N excretion was 257 (SD 49) mg N/kg W0.75 per d. Both creatinine and fasting N excretions were also lower than in cattle. The activities of xanthine oxidase (EC 1.2.3.2) in plasma, liver and intestinal mucosa were determined in buffaloes, cattle and sheep. Xanthine oxidase activities in buffaloes were 24·5 (SD 2·7) unit/l plasma and 0·44 (SD 0·02) and 0·31 (SD 0·10) unit/g fresh tissue in liver and intestinal mucosa respectively. These activities were higher than those in cattle and sheep. Xanthine oxidase was practically absent from plasma and intestine of sheep. It is suggested that the differences in PD excretion between buffaloes and cattle were probably due to the smaller proportion of plasma PD that was disposed of in the urine of buffaloes.

The endogenous urinary excretion of the purine derivatives allantoin, uric acid and xanthine plus hypoxanthine were measured in twenty-nine lambs, ten cattle (six steers, one cow and three preruminant calves) and four pigs. The sheep and mature cattle were nourished by intragastric infusion and the calves were given a milk-substitute. The pigs were fed on a purine-free diet. The excretion of total purine derivatives was substantially greater by the cattle, being 514 (se 20.6) μmol/kg live weight (W)0·75 per d compared with 168 (se 5·0) μmol/kg W0·75 per d by the sheep and 166 (se 2·6) μmol/kg W0·75 per d by the pigs. Plasma from normally fed sheep, cows and pigs was incubated with either xanthine or uric acid. Sheep and pig plasma had no xanthine oxidase (ec 1. 2. 3. 2) activity whereas plasma from cattle did. Uricase (ec 1. 7. 3. 3) was not present in plasma of cattle and pigs and appeared to be present in trace amounts only in sheep plasma. It is suggested that the species differences in endogenous purine derivative excretion were probably due to the different profiles of xanthine oxidase activity in tissues and particularly in the blood. This is because a high xanthine oxidase activity in tissues and particularly in the blood. This is because a high xanthine oxidase activity would reduce the chance to recycle purines, by increasing the probability of degradation to compounds which could not be salvaged.