Effect of P-glycoprotein on the transmembrane absorption and metabolism of quercitrin on Caco-2 cells / 国际药学研究杂志

Objective To explore the role of P-glycoprotein(P-gp)on cellular uptake and metabolism in the transmembrane transport of quercitrin.Methods Caco-2 cell monolayer and P-gp inhibitor Cyclosporin A(CysA)were used in the study.Quercitrin, quercetin,isorhamnetin and tamarixetin were determined by LC-MS to study cellular uptake and metabolism of quercitrin on Caco-2 cells.Results Uptake of quercitrin by Caco-2 cells:in different concentration groups of quercitrin coincubating with and without Cy?sA,intracellular accumulation presented the following characteristics:the amount of quercitrin first rose,reached the peak in 60 min and then declined to a steady-state in 120 min.And meanwhile there were significant differences between the two different processing groups incubating with and without CysA(P<0.05);quercetin was detected in all groups(3.0,9.0 and 27.0 mg/L).But in the higher concentration groups incubating with and without CysA,the intracellular quercetin presented a characteristics similar to its original glycosides and showed a significant difference(P<0.05),while the other groups showed no concentration-and time-dependence.At the same time,isorhamnetin and tamarixetin were detected in two higher concentration groups incubating with and without CysA, which showed the trend similar to the original glycosides but no significant difference was obtained between the two processing groups(P>0.05).Isorhamnetin and tamarixetin were not detected in the low and middle concentration groups.Transmembrane transport:on the basal lateral of all groups,the content of the quercitrin in 150 min incubation time showed a trend of continuous rise,and there was no significant difference between the two processing groups.Quercetin,isorhamnetin and tamarixetin were not detected.Conclu?sion Intact quercitrin could be absorbed into the Caco-2 cells and transported across the Caco-2 cell monolayer,and suffered a series of further metabolism in the Caco-2 cells and the basal side of Caco-2 cell monolayer,leading to different characteristics between intra?cellular accumulation and transmembrane transport.P-gp reduces the transmembrane transport of quercitrin by its efflux function,but did not involved in quercitrin metabolism.

The metabolic changes of mice serum after loaded swimming / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the metabolic changes of mice serum after loaded swimming and to provide a basis for the study of anti-fatigue functional food.</p><p><b>METHODS</b>The male Kunming mice were randomly divided into four group, fed an AIN-93 diet for 14 days, and forced to swim for 30, 60 or 120 min, respectively, with a load on their tails. The mice were executed after swimming immediately and the changes of serum metabolic profiles were analyzed using metabolomic approach. The spectrum was acquired by using Carr Purcell Meiboom Gill (CPMG) or Longitudinal Eddy Current Delay (LED) sequence, and transformed into 1H NMR spectrogram via Fourier transformation. All the data were analyzed by principal component analysis by using the SIMCA-P+ software.</p><p><b>RESULTS</b>The serum metabolic profiles changed significantly after loaded swimming. Serum beta-hydroxybutyric acid, acetate, lactate, lipid were increased and glucose, choline, phosphorylcholine, alanine and phosphatidylcholine decreased. These changes were time dependent.</p><p><b>CONCLUSION</b>The changes of serum metabolic profiles after loaded swimming were time dependent, especially for lipid metabolite.Further study based on the interaction of choline and lipid metabolism may contribute to understand the mechanism of fatigue.</p>

Improvement effect of vitamins B1, B2 and PP supplementation on substance metabolism of mice exposed to acute hypoxia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the improvement effect of vitamins B1, B2, PP supplementation to the metabolism changes of carbohydrates, lipids, protein and energy in mice exposed to acute hypoxia.</p><p><b>METHODS</b>Fifty male Kunming mice were randomly divided into normal, acute hypoxia, acute hypoxia plus 2 times, 4 times and 8 times vitamins B1, B2, PP supplemented groups. All mice were fed corresponding diets for two weeks and then except the normal group were exposed to a simulated altitude of 6 000 meters for 8 hours. The changes of glucose, pyruvate, lactate, urea nitrogen, free fatty acids and beta-hydroxybutyric acid from serum, liver glycogen and blood adenosine triphosphate (ATP) concentration were measured.</p><p><b>RESULTS</b>After being exposed to acute hypoxia, the mice glucose, liver glycogen, pyruvate, lactate, free fatty acids, beta-hydroxybutyric acid and urea nitrogen level were increased significantly (P < 0.05), while blood ATP concentration was decreased. In the vitamins B1, B2 and PP supplemented groups, these changes were improved.</p><p><b>CONCLUSION</b>The significant changes in carbohydrate, lipid and protein metabolism were observed in mice exposed to acute hypoxia, and the supplementation of vitamins B1, B2 and PP was proved to be beneficial in improving some metabolic pathways. It is suggested that the supplemented dose of four times was good.</p>

Metabolomic study on vitamins B₁, B₂, and PP supplementation to improve serum metabolic profiles in mice under acute hypoxia based on ¹H NMR analysis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To explore metabolic changes after acute hypoxia and modulating effect of vitamins B₁, B₂, and PP supplementation in mice exposed to acute hypoxia.</p><p><b>METHODS</b>Fifty male Kunming mice were randomly divided into 5 groups: normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time-vitamins B₁, B₂, and PP supplementation. All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6,000 meters for 8 h, except for the normal group. Nuclear magnetic resonance analysis was used to identify the changes of serum metabolic profiles.</p><p><b>RESULTS</b>There were significant changes in some serum metabolites under induced acute hypoxia, essentially relative increase in the concentrations of lactate, sugar and lipids and decrease in ethanol. The serum levels of choline, succinate, taurine, alanine, and glutamine also increased and phosphocholine decreased in the acute hypoxia group. After vitamins B₁, B₂, and PP supplementation, all these metabolic changes gradually recovered.</p><p><b>CONCLUSIONS</b>Significant changes in serum metabolic profile were observed by metabolomics in mice exposed to acute hypoxia, and vitamins B₁, B₂, and PP supplementation proved to be beneficial to improving some metabolic pathways. It is suggested that the dietary intakes of vitamins B₁, B₂, and PP should be increased under hypoxia condition.</p>

Effects of acute hypoxia on plasma metabolome in mice / 中国应用生理学杂志

<p><b>AIM</b>To explore the metabolic effects of acute hypoxia on mice plasma.</p><p><b>METHODS</b>Fourteen mice were randomly divided into two groups: control and hypoxia group. The mice of hypoxia group were exposed to a simulated altitude of 6000 meters for 8 hours. Nuclear magnetic resonance spectrometer was used to identify the metabolic changes after acute hypoxia.</p><p><b>RESULTS</b>Compared with control, the most notable significantly after acute hypoxia exposure. remarkably and lactate increased metabolic changes in plasma were as follows: camrnitine decreased levels of lipids and pyruvate, alanine, taurine, Decreases in levels of beta-HB, ethanol glycerol, glutamate, glycine and serine, and increased choline, glucose, and glutamine were also observed in hypoxia group.</p><p><b>CONCLUSION</b>Significant changes in the plasma carbohydrate, lipid and amino acid profiles were observed following acute hypoxia, suggesting a hypoxia-induced alteration in energy and related substances metabolism.</p>

Intervention of nutritional status and hypoxia endurance by a nutritional supplement in young adults living at high altitude / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of a nutritional supplement on nutritional status and hypoxia endurance in young adults living at high altitude.</p><p><b>METHODS</b>Forty healthy male young adults were recruited and randomly assigned to control and intervention groups. The nutrition survey was carried out using weighing method. The intervention group was given a nutritional supplement specifically designed for use at high altitude, while the control group was treated with a supplement made of stir-fried flour. After 20 days of supplementation, they marched from the altitude of 3700 m to 5100 m. The changes in HR, SaO2, serum concentrations of VA and VB2 and some minerals were measured.</p><p><b>RESULTS</b>The results of nutrition survey showed that the ratio of three macronutrients was not adequate and the intakes of calcium, VA and VB2 were below Chinese RNI. The serum concentrations of calcium, magnesium and VA were below normal references. The serum VB2 concentration was at the low level o f normal reference. The nutritional supplement could increase the serum concentrations of calcium, magnesium, VA and VB2, indicating an improved nutritional status. The changes in HR and SaO2 were diminished in intervention group compared with control group.</p><p><b>CONCLUSION</b>The nutritional supplement can improve nutritional status and increase the hypoxia endurance in young adults living at high altitude.</p>

Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities / 中华预防医学杂志

<p><b>OBJECTIVE</b>To observe the effects of fruit juices with different antioxidant capacity on antioxidant system function of aged rats.</p><p><b>METHODS</b>Thirty Wistar rats were randomly divided into three groups: pomegranate juice and apple juice as two experimental groups, while distilled water as normal control group. They were administrated fruit juices or distilled water respectively by gavage daily for 4 weeks. At the end of experiment, the antioxidant system function was assessed.</p><p><b>RESULTS</b>The aged rats in pomegranate juice group showed significantly higher serum antioxidant capacity (0.90 +/- 0.13) mmol/L than that in control group (0.79 +/- 0.10) mmol/L (P < 0.05). The concentrations of serum carbonyl and oxLDL were decreased significantly in pomegranate juice group as compared to the control group (P < 0.05). The percentage of injured blood lymphocyte DNA and the ratio of tail length/total length were declined significantly in pomegranate juice group (P < 0.05 and P < 0.01 respectively). The apple juice showed no effects except decreased ratio of tail length/total length of injured lymphocyte DNA. There were no changes in concentrations of serum vitamin C, vitamin E, urinary 8-OH-dG excretion and the activities of serum SOD, GSH-Px, CAT among three groups.</p><p><b>CONCLUSIONS</b>The pomegranate juice should possess higher antioxidant capacity and might improve the antioxidant system function of aged rats, while the apple juice is relatively lower in antioxidant capacity and not very effective. The polyphenols in pomegranate juice might be the important functional components.</p>

The regulatory effects of arginine on hepatic insulin-like growth factor-1 secretion in rats and its implication / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the regulatory effect of arginine on the secretion of hepatic insulin-like growth factor-1 (IGF-I), and the mechanism of enhancing the immune function by arginine.</p><p><b>METHODS</b>Wistar rats were randomly divided into normal control (NC), wound control (WC), and wound with arginine (Arg) groups, with 8 rats in each group. The rats in WC and Arg groups were inflicted with soft tissue trauma on the back. The rats in Arg group were fed a diet supplemented with 5% arginine for one week, while those in NC and WC groups were fed with glycine. The serum contents of arginine, ornithine, growth factor (GH), NO and IGF-I were determined 7 days after feeding. T cell proliferation and IGF-I mRNA expression in hepatic tissue were also measured. Meanwhile, the rat hepatocytes were cultured in serum-free medium containing different concentrations of arginine. The supernatant was collected for the determination of IGF-I level.</p><p><b>RESULTS</b>1). There was no obvious difference of the serum level of arginine and ornithine between NC and WC groups (P > 0.05), but the contents of them were obviously higher in the Arg group compared with other two groups (P < 0.01). 2). No difference in the serum GH level was found among all the groups (P > 0.05), but the serum NO content in WC and Arg groups was significantly lower than that in NC group (P < 0.01), and the serum IGF-I content in WC group decreased obviously compared with that in NC group (P < 0.01). 3). The thymocyte proliferation rate in WC group was also markedly lower than that in NC group (P < 0.01), but that in Arg group was improved compared with WC group (P < 0.01). 4). The expression of hepatic IGF-I mRNA: The relative value of IGF-I mRNA was 1.19 +/- 0.06, 1.08 +/- 0.06 and 1.29 +/- 0.06 in NC, WC and Arg, respectively, while the value in WC was lower than that in NC (P < 0.05) group, and that in Arg group was much higher than that in WC group (P < 0.01). 5). The IGF-I level in the supernatant of cultured hepatocytes: When Arg concentration was 0.0750, 0.7500, 7.5000 mmol/L in the culture medium, the IGF-I level in the supernatant of hepatic cell medi-um was obviously higher than that in the medium without arginine (P < 0.01). Although IGF-I level decreased in the culture medium with arginine in the dose of 37.5000 mmol/L, it was still obviously higher than that in the medium without arginine (P < 0.01).</p><p><b>CONCLUSION</b>Arginine could also produce the immune enhancing effect by stimulating hepatic IGF-I secretion.</p>

Protection against hepatic ischemia-reperfusion injury in rats by oral pretreatment with quercetin / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats.</p><p><b>METHODS</b>The quercetin (0.13 mmol/kg) was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography (HPLC). Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) activities and malondialdehyde (MDA) concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione (GSH), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO), total antioxidant capacity (TAOC), contents of reactive oxygen species (ROS) and MDA, DNA fragmentation were also determined.</p><p><b>RESULTS</b>Hepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT, GOT activities and MDA concentration after hepatic ischemia-reperfusion injury were reduced significantly by pretreatment with quercetin. Hepatic content of GSH and activities of SOD, GSH-Px and TAOC were restored remarkably while the ROS and MDA contents were significantly diminished by quercetin pretreatment after ischemia-reperfusion injury. However, quercetin pretreatment did not reduce significantly hepatic XO activity and DNA fragmentation. Ascorbic acid pretreatment had also protective effects against hepatic ischemia-reperfusion injury by restoring hepatic content of GSH, TAOC and diminishing ROS and MDA formation and DNA fragmentation.</p><p><b>CONCLUSION</b>It is indicated that quercetin can protect the liver against ischemia-reperfusion injury after oral pretreatment and the underlying mechanism is associated with improved hepatic antioxidant capacity.</p>

Comparative study on the antioxidant capacity of quercetin in vivo and in vitro / 中国应用生理学杂志

<p><b>AIM</b>To compare the TAOC of quercetin, rutin, vitamin C, vitamin E in vitro and examine the effect of quercetin on TAOC of rat plasma after intragastric administration.</p><p><b>METHODS</b>Fe3+ reducing ability assay, UV spectrum analysis and HPLC analysis were used to measure TAOC of plasma and the contents of quercetin and rutin after intragastric administration.</p><p><b>RESULTS</b>The TAOC of quercetin was stronger than that of rutin and roughly equal to vitamin C and vitamin E in vitro. After intragastric administration of quercetin (40 mg/kg bw), the TAOC and content of quercetin in rat plasma increased significantly. Vitamin C also increased plasma TAOC significantly, but rutin and vitamin E didn't after intragastric administration. However, there was no remarkable absorption peak of quercetin on HPLC chromatograms and on the other hand, the peak areas of two unknown peaks near quercetin peak were increased after intragastric administration of quercetin.</p><p><b>CONCLUSION</b>The antioxidant capacity of quercetin was stronger than rutin and comparable to vitamin C both in vitro and in vivo. After absorption, quercetin is metabolized to its derivatives.</p>