5-Hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone: a pancreatic lipase inhibitor isolated from Alpinia officinarum. (65/335)

A pancreatic lipase inhibitor, 5-hydroxy-7-(4'-hydroxy-3'-methoxyphenyl)-1-phenyl-3-heptanone (HPH), from the rhizome of Alpinia officinarum (AO) was isolated and its antihyperlipidemic activity was measured. HPH inhibited a pancreatic lipase with an IC(50) value of 1.5 mg/ml (triolein as a substrate). HPH significantly lowered the serum TG level in corn oil feeding-induced triglyceridemic mice, and reduced serum triglyceride (TG) and cholesterol in Triton WR-1339-induced hyperlipidemic mice. However, HPH did not show hypolipidemic activity in high cholesterol diet-induced hyperlipidemic mice. Based on these findings, we propose that PL inhibitors may be effective as hypolipidemic agents.  (+info)

Fish oil increases antioxidant enzyme activities in macrophages and reduces atherosclerotic lesions in apoE-knockout mice. (66/335)

OBJECTIVES: The molecular and cellular mechanisms that fish oil (FO) exerts its physiological function are complicated. The present study brings evidence on the in vivo effect of FO on the development of atherosclerosis in apolipoprotein E knockout (apoE(-/-)) mice. We also test the hypothesis that the modulation of the cellular oxidative stress and antioxidant status contributes to the anti-atherosclerotic effect of FO. METHODS AND RESULTS: ApoE(-/-) mice were fed a diet rich either in FO or corn oil (CO) for 10 weeks. Both FO and CO had a plasma triacylglycerol-raising effect in apoE(-/-) mice, whereas aortic atherosclerotic lesions were significantly reduced in the mice that had consumed a high FO diet compared to those fed a high CO diet. The levels of hepatic superoxide dismutase (SOD) and catalase (CAT) activities were remarkably higher in the mice fed the FO diet than in mice fed the CO diet and the control diet. We then investigated the effects of FO and CO on the production of superoxide anion (O2*-)) and reactive oxygen species (ROS) in cultured J774 macrophages. Antioxidant status was assessed by the determination of antioxidant enzyme activities. Both FO and CO induced high levels of O2*-) and total ROS at a short time in macrophages. However, only the FO group restored the induction of O2*-) and ROS to near basal levels after oil treatment for 24 h. Throughout the time course experiments, antioxidant enzyme activities in the FO group mostly displayed a greater increase than in the corresponding CO group after the same time period of oil treatment. CONCLUSIONS: In the present study, FO reduced the formation of atherosclerotic lesions in the aortic arteries of apoE(-/-) mice not through any lipid-lowering effect. The protective role of FO in the development of atherosclerosis may result from its antioxidative defense mechanism through the induction of antioxidant enzyme activities.  (+info)

Evaluation of a rat model versus a physiologically based extraction test for assessing phenanthrene bioavailability from soils. (67/335)

The soil matrix can impact the bioavailability of soil-bound organic chemicals, and this impact is governed in part by soil properties such as organic carbon (OC) content, clay minerals, and pH. Recently, a physiologically based extraction test (PBET) was developed to predict the bioavailability of soil-bound organic chemicals. In the current study, the bioavailability of phenanthrene (PA) from laboratory-treated soils varying in OC content, clay, and pH was investigated using an in vivo rat model and an in vitro PBET. The relationship between these two approaches was also examined. In the in vivo assay, soils and corn oil containing equivalent levels of PA were administered to Sprague-Dawley rats by gavage at two dose levels: 400 and 800 mg/kg body weight. Equivalent doses were given via intravenous injection (i.v.). The areas under the blood concentration-versus-time curves (AUC) were measured, and the absolute and relative bioavailabilities of PA were determined for each soil. In the PBET tests, one g of each soil was extracted by artificial saliva, gastric juice, duodenum juice, and bile. The fraction of PA mobilized from each soil was quantified. The AUCs of PA in all soils were significantly lower than those following iv injection (p < 0.05), indicating that the soil matrix could reduce the bioavailability of PA from soil. There were obvious trends of soils with higher OC content and clay content, resulting in the lower bioavailability of PA from soil. A significant correlation (p < 0.05) was observed between the fraction of PA mobilized from soil in the PBET and its in vivo bioavailability. The data also showed that the absolute bioavailability of PA from corn oil was low: approximately 25%. These results suggest that PBET assay might be a useful alternative in predicting bioavailability of soil-bound organic chemicals. However, due to the limited soil types and use of one chemical vs. a variety of contaminants and soil properties in the environment, further efforts involving more chemicals and soil types are needed to validate this surrogate method.  (+info)

Dietary saturated fat reduces alcoholic hepatotoxicity in rats by altering fatty acid metabolism and membrane composition. (68/335)

Rats fed a saturated fat diet are protected from experimentally induced alcoholic liver disease, but the molecular mechanisms underlying this phenomenon remain in dispute. We fed male Sprague-Dawley rats intragastrically by total enteral nutrition using diets with or without ethanol. In 1 control and 1 ethanol group, the dietary fat was corn oil at a level of 45% of total energy. In other groups, saturated fat [18:82 ratio of beef tallow:medium-chain triglyceride (MCT) oil] was substituted for corn oil at levels of 10, 20, and 30% of total energy, while keeping the total energy from fat at 45%. After 70 d, liver pathology, serum alanine aminotransferase (ALT), biochemical markers of oxidative stress, liver fatty acid composition, cytochrome P450 2E1 (CYP2E1) expression and activity and cytochrome P450 4A (CYP4A) expression were assessed. In rats fed the corn oil plus ethanol diet, hepatotoxicity was accompanied by oxidative stress. As dietary saturated fat content increased, all measures of hepatic pathology and oxidative stress were progressively reduced, including steatosis (P < 0.05). Thus, saturated fat protected rats from alcoholic liver disease in a dose-responsive fashion. Changes in dietary fat composition did not alter ethanol metabolism or CYP2E1 induction, but hepatic CYP4A levels increased markedly in rats fed the saturated fat diet. Dietary saturated fat also decreased liver triglyceride, PUFA, and total FFA concentrations (P < 0.05). Increases in dietary saturated fat increased liver membrane resistance to oxidative stress. In addition, reduced alcoholic steatosis was associated with reduced fatty acid synthesis in combination with increased CYP4A-catalyzed fatty acid oxidation and effects on lipid export. These findings may be important in the nutritional management and treatment of alcoholic liver disease.  (+info)

Medium-chain triglycerides enhance secretory IgA expression in rat intestine after administration of endotoxin. (69/335)

The purpose of this study was to determine whether medium-chain triglycerides (MCTs) modulate the inflammatory immune response to LPS and enhance the expression of secretory IgA in the rat intestine. Rats were given either corn oil or MCTs by gavage daily for 1 wk, and LPS or saline vehicle was administered via the tail vein. They were then killed, and serum and sections from the gut were collected for further analysis. Western blot analysis for secretory IgA revealed that MCTs significantly enhanced its expression in the ileum compared with corn oil in rats administered saline. After LPS challenge, expression of secretory IgA was decreased in the corn oil group but not in the MCTs group. The mRNA expression of IL-6 was assessed by real-time RT-PCR, because IL-6 regulates secretory IgA in the intestine. The expression was significantly greater in the MCTs group than in the corn oil group after LPS injection. Increases in expression of proinflammatory cytokines or chemokines such as TNF-alpha, IL-18, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 in the ileum were significantly blunted by MCTs. In addition, the mRNA expression of the Th2 IgA-stimulating cytokine IL-10 in the ileum and Peyer's patches was significantly greater in the MCTs than the corn oil group. In contrast, the mRNA expression of the Th1 IgA-inhibiting cytokine interferon-gamma was blunted by MCTs. As a result, intestinal injury was significantly reduced. Therefore, MCTs protect the gut by modulating the immune response to LPS and enhancing secretory IgA expression.  (+info)

Effects of supplemental rumen-protected conjugated linoleic acid or corn oil on fatty acid composition of adipose tissues in beef cattle. (70/335)

Thirty-six Angus x Hereford heifers (365 +/- 60 kg) were used to determine the effects of supplemental dietary lipid sources on fatty acid composition of i.m., perianal (p.a.), and s.c. lipid depots. Lipid was supplied to diets as either corn oil or a rumen-protected conjugated linoleic acid (CLA) salt for two specific treatment periods of either the final 32 or 60 d on feed. Following an initial 56-d feeding period, heifers were fed one of three dietary treatments (DM basis): 1) basal diet containing 88% concentrate and 12% grass hay (CON), 2) basal diet plus 4% corn oil (OIL), or 3) basal diet plus 2% rumen-protected CLA salt (RPCLA) containing 31% CLA. The trans-10, cis-12 CLA concentration was greatest (P < 0.05) for heifers fed RPCLA and OIL diets and least (P < 0.05) for CON, regardless of time on dietary treatment. Heifers fed supplemental RPCLA had greater (P < 0.05) total CLA content than either CON- or OIL-fed heifers. Adipose tissue concentration of trans-11 vaccenic acid (TVA) was less (P < 0.05) for CON than OIL or RPCLA, which did not differ (P > 0.05). Percentages of C18:1 trans-10 were least (P < 0.05) in i.m. lipid compared with p.a. and s.c., which did not differ (P > 0.05). Following 60 d of lipid supplementation, heifers fed OIL and RPCLA had lower (P < 0.05) concentrations of oleic acid and total monounsaturated fatty acids (MUFA) compared with CON. The ratio of cis-9, trans-11 CLA:TVA was higher (P < 0.05) for heifers fed 60 vs. 32 d, but did not differ (P > 0.05) between adipose depots. Feeding OIL increased (P < 0.05) adipose concentration of C18:2 fatty acid, whereas feeding RPCLA increased (P < 0.05) total CLA isomers by 22%. Intramuscular lipid contained the lowest (P < 0.05) percentage of cis-9, trans-11 CLA, total CLA, C18:1 cis-9, C18:1 trans-10, and TVA. Total CLA and cis-9, trans-11 CLA isomers were increased (P < 0.05) in p.a. and s.c. adipose depots, whereas i.m. adipose tissue contained increased (P < 0.05) amounts of total PUFA. Results from this study indicate that short-term lipid supplementation to feedlot cattle can increase adipose tissue CLA concentrations, but only marginally (8.3 to 17.5%). Moreover, observed decreases in oleic acid and total MUFA concentrations of adipose tissues from heifers fed rumen-protected CLA or corn oil suggest that lipid supplementation may decrease delta9 desaturase activity in adipose tissues, which in turn would lower the conversion of TVA to cis-9, trans-11 CLA isomer.  (+info)

Effect of dietary supplementation with n-3 polyunsaturated fatty acids on physical properties and metabolism of low density lipoprotein in humans. (71/335)

The effects of marine n-3 polyunsaturated fatty acids were investigated in relation to the chemical and physical properties of low density lipoprotein (LDL) and how these changes affected LDL metabolism in humans. The subjects received supplements of six capsules daily, each capsule containing 1 g of either highly concentrated ethyl esters of n-3 fatty acids (85% eicosapentaenoic acid and docosahexaenoic acid) (n = 12) or corn oil (56% linoleic and 26% oleic acid) (n = 11). After 4 months of oil supplementation, the following changes were observed in the lipid moiety of the n-3-enriched LDL particles compared with LDL from the corn oil group: LDL cholesteryl ester, as well as the amount of total lipids of LDL, was significantly lower (0.97 +/- 0.12 versus 1.19 +/- 0.23 mg/mg protein and 1.88 +/- 0.40 versus 2.45 +/- 0.31 mg/mg, respectively; mean +/- SD, n = 6, p less than 0.05); the amount of eicosapentaenoic and docosahexaenoic acids and the unsaturation index increased (104.0 versus 29.4 micrograms/mg protein and 6.64 versus 5.49, respectively); and differential scanning calorimetry showed that LDL cholesteryl ester melting temperature was lowered by 2 degrees C (27.6 +/- 0.8 degrees versus 29.5 +/- 0.2 degrees C). The only effect observed on the protein moiety was an increase in the ratio of apolipoprotein (apo) B to cholesterol (0.66 +/- 0.17 versus 0.82 +/- 0.14 mg/mg cholesterol; p less than 0.05). Circular dichroism spectra of LDL indicated an alpha-helix content of 46 +/- 5% in apo B from both groups. No difference was observed by 13C nuclear magnetic resonance spectroscopy in the ratio of "active" to "normal" lysine residues of apo B. No detectable differences in the size of n-3 fatty acid-enriched LDL particles versus control LDL could be measured by either electron microscopy of negatively stained LDL (24.5 +/- 2.0 versus 25.0 +/- 1.5 nm) or dynamic light scattering (24.9 +/- 0.9 versus 24.9 +/- 0.4 nm). LDL from the fish oil and corn oil groups showed similar susceptibility to Cu(2+)-catalyzed lipid peroxidation, as indicated by the amount of lipid peroxides formed during the oxidation time, and degradation of oxidatively modified LDL in J774 macrophages as a function of Cu2+ oxidation time. No effect of n-3 fatty acids was observed on LDL metabolism. Specific uptake and degradation of n-3 fatty acid-enriched LDL were similar to those for control LDL in HepG2 cells as well as in human skin fibroblasts, and they showed the same ability to stimulate cholesteryl ester synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)  (+info)

Docosahexaenoic and eicosapentaenoic acids in plasma phospholipids are divergently associated with high density lipoprotein in humans. (72/335)

The effect of fish oil rich in eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on serum lipoprotein concentrations is not clear, and it is not known whether EPA and DHA are similarly related to serum lipid or lipoprotein levels. We conducted a randomized, 10-week, dietary supplementation trial in which the effects of 6 g per day of 85% EPA and DHA were compared with 6 g per day of corn oil in 156 men and women. Multivariate analyses were used to assess independent relations between plasma phospholipid EPA and DHA and serum lipoprotein levels. In the fish oil group triglycerides fell 21% (p less than 0.001) and high density lipoprotein cholesterol (HDL-C) rose 3.8% (p less than 0.05). In the corn oil group triglycerides did not change, but HDL-C rose 6.1% (p less than 0.01). Compared with fish oil, apolipoprotein A-I (apo A-I) rose 5.1% after corn oil intake (p less than 0.05). Plasma EPA and DHA levels rose after fish oil intake and fell after corn oil intake (all p less than 0.001). The change (delta) in EPA was inversely correlated with delta triglycerides (p = 0.035) and positively correlated with delta HDL-C and delta apo A-I (both p less than 0.001) in the multivariate analyses. In contrast, delta DHA was not correlated with delta triglycerides but was inversely correlated with delta HDL-C and delta apo A-I (both p less than 0.001). Standardizing for DHA removed the difference in apo A-I levels between groups. This study suggests that EPA and DHA are divergently associated with HDL, possibly through different mechanisms.  (+info)