Reduced Cholesterol Concentrations Research Articles

Thicker Shell Eggs with Enriched N-3 Polyunsaturated Fatty Acids and Lower Yolk Cholesterol Contents, as Affected by Dietary Nettle (Urtica cannabina) Supplementation in Laying Hens.

Simple SummaryThe nettle Urtica cannabina (U. cannabina) belongs to the Urticaceae (nettle) family in the major group Angiosperms (flowering plants); it is distributed worldwide in temperate regions. While it was previously considered to be a weed, increasing evidence suggests that it is a valuable nutrient resource and has multiple biological functions when included in both human and animal diets. U. cannabina was given to laying hens in this experiment to study its effect on the hens’ performance, egg quality, yolk fatty acids composition, and serum biochemical parameters. The results revealed that dietary supplementation with U. cannabina has the potential to produce high-quality eggs. The data collected in this experiment can be used to inform further use of this plant to improve the lipid profile and fatty acid composition of eggs produced by hens fed on U. cannabina.The nettle Urtica cannabina (U. cannabina) is not only a functional edible food for humans but also a potential alternative feed resource for poultry, providing protein, fatty acids, vitamins, and minerals. The present study was conducted to evaluate the effects of dietary U. cannabina on the production of high-quality eggs with enriched n-3 polyunsaturated fatty acids (PUFA) and lower cholesterol contents. One hundred and twenty laying hens were assigned to three groups [control, 15% alfalfa meal supplementation (TRTA), and 15% U. cannabina supplementation (TRTU)]. The results showed that the feed intake, yolk color, and shell thickness were increased (p < 0.05) in the U. cannabina group. Moreover, cholesterol contents of the yolk and serum were lower in the U. cannabina group (p < 0.05). The total n-3 PUFA concentration in the yolk was increased while the ratio of n-6/n-3 was reduced in the U. cannabina group (p < 0.01). In conclusion, the dietary inclusion of U. cannabina increased shell thickness, yolk n-3 PUFA levels, and yolk color, and reduced cholesterol contents of the yolk and serum without any negative impacts on health or laying performance.

Downregulation of Cyp7a1 by Cholic Acid and Chenodeoxycholic Acid in Cyp27a1/ApoE Double Knockout Mice: Differential Cardiovascular Outcome.

Sterol 27-hydroxylase (CYP27A1) is a key enzyme in bile acids (BAs) biosynthesis and a regulator of cholesterol metabolism. Cyp27a1/Apolipoprotein E double knockout (DKO) mice fed with western diet (WD) are protected from atherosclerosis via up-regulation of hepatic Cyp7a1 and Cyp3a11. Since feeding BAs ameliorates metabolic changes in Cyp27a1 KO mice, we tested BAs feeding on the development of atherosclerosis in DKO mice. DKO mice were fed for 8 weeks with WD containing 0.1% cholic acid (CA) (WD-CA) or chenodeoxycholic acid (CDCA) (WD-CDCA). Atherosclerotic lesions, plasma lipoprotein composition and functionality, hepatic lipid content, BAs amount and composition, expression of genes involved in lipid metabolism and BA signaling in liver and intestine as well as intestinal cholesterol absorption were assessed. Hepatic Cyp7a1 and Cyp3a11 expression were reduced by 60% after feeding with both WD-CA and WD-CDCA. After feeding with WD-CA we observed a 40-fold increase in the abundance of atherosclerotic lesions in the aortic valve, doubling of the levels of plasma total and low density lipoprotein cholesterol and halving of the level of high density lipoprotein cholesterol. Furthermore, in these mice plasma cholesterol efflux capacity decreased by 30%, hepatic BA content increased 10-fold, intestinal cholesterol absorption increased 6-fold. No such changes were observed in mice fed with WD-CDCA. Despite similar reduction on Cyp7a1 and Cyp3a11 hepatic expression, CA and CDCA have a drastically different impact on development of atherosclerosis, plasma and hepatic lipids, BAs composition and intestinal absorption. Reduced cholesterol absorption contributes largely to athero-protection in DKO mice.

Atorvastatin Enhances Foam Cell Lipophagy and Promotes Cholesterol Efflux Through the AMP-Activated Protein Kinase/Mammalian Target of Rapamycin Pathway.

Foam cells are the main pathological components of atherosclerosis. Therapies reducing foam cell formation can effectively prevent atherosclerotic diseases and cardiovascular events. Beyond lowering plasma cholesterol levels, the pleiotropic functions of statins in atherosclerosis have not been fully elucidated. In the present study, atorvastatin reduced cholesterol content and increased cholesterol efflux from foam cells in a concentration-dependent manner. Atorvastatin (10 μM) inhibited foam cell formation within 48 hours. Furthermore, we found that atorvastatin inhibited foam cell formation by promoting lipophagy, which was manifested by increased autophagy-related gene 5 (Atg5) expression, elevated ratio of microtubule-associated protein1 light chain 3 (LC3) II to LC3I, reduced p62 expression, and increased LC3 and lipid droplets colocalization in foam cells treated with atorvastatin. The autophagy inducer, rapamycin (Rap), did not increase the lipophagy enhancement effect of atorvastatin, but the autophagy inhibitor, 3-methyladenine, suppressed the effect of atorvastatin on Atg5 expression and the LC3II/LC3I ratio, as well as the increased p62 expression, suppressed lipophagy, attenuated cholesterol efflux and increased cholesterol content in foam cells. Further analysis revealed that atorvastatin promoted lipophagy by upregulating adenosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation, and downregulating mammalian target of rapamycin phosphorylation, whereas the AMPK inhibiter, compound C, attenuated these effects. In conclusion, atorvastatin reduced lipid accumulation and promoted cholesterol efflux by enhancing lipophagy in foam cells and thereby inhibited foam cell formation. The enhanced lipophagy of foam cells was exerted through the AMPK/mammalian target of rapamycin signaling pathway.

Lowering Low-Density Lipoprotein Cholesterol Concentration with Plant Stanol Esters to Reduce the Risk of Atherosclerotic Cardiovascular Disease Events at a Population Level: A Critical Discussion.

Atherosclerotic cardiovascular diseases (ASCVDs) cause every fifth death worldwide. However, it is possible to prevent the progression of ASCVDs by reducing circulating concentrations of low-density lipoprotein cholesterol (LDL-C). Recent large meta-analyses demonstrated that by reducing the dietary intake of saturated fat and cholesterol, it is possible to reduce the risk of ASCVD events. Plant stanols, as fatty-acid esters, were developed as a dietary adjunct to reduce LDL-C levels as part of a heart-healthy diet. They reduce cholesterol absorption so that less cholesterol is transported to the liver, and the expression of LDL receptors is upregulated. Ultimately, LDL-C concentrations are reduced on average by 9–12% by consuming 2–3 g of plant stanol esters per day. In this review, we discuss recent information regarding the prevention of ASCVDs with a focus on dietary means. We also present new estimates on the effect of plant stanol ester consumption on LDL-C levels and the risk of ASCVD events. Plant stanol esters as part of a heart-healthy diet plausibly offer a means to reduce the risk of ASCVD events at a population level. This approach is not only appropriate for subjects with a high risk of ASCVD, but also for subjects at an apparently lower risk to prevent subclinical atherosclerosis.

Preparation and Characterization of Chitosan/Fish Scale Collagen/Lovastatin Nanocomposites

In this study, a polymeric drug delivery system based on chitosan and fish scale collagen was fabricated in the nanometer size by the emulsification method for loading lovastatin drug—a poorly water soluble drug for the treatment of reduction of cholesterol concentration in blood. An interesting point of this work is using collagen extracted from fresh water fish scales. The characteristics, properties, morphology and drug release control ability of the chitosan/collagen/lovastatin nanocomposites were evaluated by Infrared spectroscopy (IR), Field emission scanning electron microscopy (FESEM), Dynamic light scattering (DLS) and Ultraviolet–Visible spectroscopy (UV–Vis) methods. The obtained results showed that the chitosan/collagen/lovastatin nanocomposites are in spherical shape with the size of particles ranged from 72.1 to 444.0 nm. The chitosan/collagen system can improve the solubility and bioavailability of lovastatin in simulated gastric and intestine fluids. The drug release mechanism from chitosan/collagen/lovastatin nanocomposites was complied with the Korsmeyer-Peppas model. In addition, the in vivo test on mice of chitosan/collagen/lovastatin nanocomposites to investigate their toxicity was conducted and discussed.

Short- and long-term effects on reproductive parameters of female Wistar rats after exposure to rosuvastatin starting in pre-puberty

Statins are a class of drugs that act lowering lipid levels by inhibiting cholesterol biosynthesis. Additionally, statins can act by “pleiotropic effects”, related to the inhibition of synthesis of the other mevalonate pathway products. Rosuvastatin is a third-generation statin and has shown better results in reducing cholesterol concentrations when compared to other statins. Recent studies suggest that rosuvastatin may act as an endocrine disruptor that potentially damages the hormonal axis and, consequently reproductive development and function of male rats. However, the effects of rosuvastatin exposure on rat female reproductive parameters remain unknown. In this study female rats were exposed to rosuvastatin at the doses of 0 (control), 3, or 10 mg/Kg.bw−1/day from pre-puberty to adulthood. No alterations in the female reproductive parameters were observed at a dose of 3 mg/Kg.bw−1. However, females exposed to 10 mg/Kg.bw−1 exhibited shorter estrous cycles, altered copulatory behavior, decreased serum prolactin level, and alterations in the liver, pituitary and placental weights, parameters to some extent influenced by the reproductive hormonal axis signaling pathway. On the other hand, pubertal onset, reproductive hormone levels, fertility, and histological parameters of the ovary, uterus, and placenta were unaltered by exposure to both doses of this statin. Thus, rosuvastatin exposure, at the higher dose, altered the reproductive function of female rats, probably due to the pleiotropic effects of this statin. Additional studies on the effects of this statin on female reproductive function and development are encouraged to better characterize its mode of action.

Altered Lipid Domains Facilitate Enhanced Pulmonary Vasoconstriction after Chronic Hypoxia.

Chronic hypoxia (CH) augments depolarization-induced pulmonary vasoconstriction through superoxide-dependent, Rho kinase-mediated Ca2+ sensitization. Nicotinamide adenine dinucleotide phosphate oxidase and EGFR (epidermal growth factor receptor) signaling contributes to this response. Caveolin-1 regulates the activity of a variety of proteins, including EGFR and nicotinamide adenine dinucleotide phosphate oxidase, and membrane cholesterol is an important regulator of caveolin-1 protein interactions. We hypothesized that derangement of these membrane lipid domain components augments depolarization-induced Ca2+ sensitization and resultant vasoconstriction after CH. Although exposure of rats to CH (4 wk, ∼380 mm Hg) did not alter caveolin-1 expression in intrapulmonary arteries or the incidence of caveolae in arterial smooth muscle, CH markedly reduced smooth muscle membrane cholesterol content as assessed by filipin fluorescence. Effects of CH on vasoreactivity and superoxide generation were examined using pressurized, Ca2+-permeabilized, endothelium-disrupted pulmonary arteries (∼150 μm inner diameter) from CH and control rats. Depolarizing concentrations of KCl evoked greater constriction in arteries from CH rats than in those obtained from control rats, and increased superoxide production as assessed by dihydroethidium fluorescence only in arteries from CH rats. Both cholesterol supplementation and the caveolin-1 scaffolding domain peptide antennapedia-Cav prevented these effects of CH, with each treatment restoring membrane cholesterol in CH arteries to control levels. Enhanced EGF-dependent vasoconstriction after CH similarly required reduced membrane cholesterol. However, these responses to CH were not associated with changes in EGFR expression or activity, suggesting that cholesterol regulates this signaling pathway downstream of EGFR. We conclude that alterations in membrane lipid domain signaling resulting from reduced cholesterol content facilitate enhanced depolarization- and EGF-induced pulmonary vasoconstriction after CH.

Bioavailability and Bioactivity of Alkylresorcinols from Different Cereal Products

Cereal products are the most important dietary source for energy intake and several bioactive compounds with high concentrations in the bran and the germ. Different cereal products provide a rich source of bioactive phytochemicals, namely, phenolic acids, carotenoids, tocopherols, alkylresorcinols, benzoxazines, phytosterols, and lignans. The bioactive substance alkylresorcinols (ARs) present in the whole cereal can inhibit enzyme activity, prevent bacterial or fungal infection, reduce cholesterol absorption, prevent cancer, and resist oxidation. In this paper, we discussed the biological activity of ARs in whole cereal products. Understanding the effects of processing on cereal phytochemicals will help us to develop improved processes for processing cereal foods with higher retention rates of bioactive compounds.

Study on the interaction between catechin and cholesterol by the density functional theory

AbstractCatechin – a natural polyphenol substance – has excellent antioxidant properties for the treatment of diseases, especially for cholesterol lowering. Catechin can reduce cholesterol content in micelles by forming insoluble precipitation with cholesterol, thereby reducing the absorption of cholesterol in the intestine. In this study, to better understand the molecular mechanism of catechin and cholesterol, we studied the interaction between typical catechins and cholesterol by the density functional theory. Results show that the adsorption energies between the four catechins and cholesterol are obviously stronger than that of cholesterol themselves, indicating that catechin has an advantage in reducing cholesterol micelle formation. Moreover, it is found that the molecular interactions of the complexes are mainly due to charge transfer of the aromatic rings of the catechins as well as the hydrogen bond interactions. Unlike the intuitive understanding of a complex formed by hydrogen bond interaction, which is positively correlated with the number of hydrogen bonds, the most stable complexes (epicatechin–cholesterol or epigallocatechin–cholesterol) have only one but stronger hydrogen bond, due to charge transfer of the aromatic rings of catechins.

Therapeutic potentials of n-hexane extracts of the three medicinal mushrooms regarding their anti-colon cancer, antioxidant, and hypocholesterolemic capabilities

Abstract. Daba GM, Elkhateeb WA, El-Dien AN, Ahmed EF, El Hagrassi AM Fayad W, Wen TC. 2020. Therapeutic potentials of n-hexane extracts of the three medicinal mushrooms regarding their anti-colon cancer, antioxidant, and hypocholesterolemic capabilities. Biodiversitas 21: 2437-2445. Evaluating in vitro biological activities of the medicinal mushrooms Hericium erinaceus, Metacordyceps neogunnii, and Dictyophora indusiata n-hexane extracts revealed their capabilities as promising therapeutic sources. By assessing their DPPH radical scavenging activities, D. indusiata extract exhibited the highest antioxidant activity (87.8±1.2%) followed by H. erinaceus, then M. neogunnii 84.9±1.6%, and 77.3±1.3%, respectively. On the other hand, M. neogunnii extract exerted promising anti-colon cancer (68.6±3.6% cytotoxicity) against HCT116 human colon cancer cell lines at concentration 100 μg/mL, whereas H. erinaceus and D. indusiata extracts exhibited weaker cytotoxic effects (18.3±1.7%, and 19.3±3.2%, respectively) using the same concentration. Investigating cholesterol reduction activities (CRA%) of the extracts revealed that activity depends on both extract concentration and incubation period. After 96 h of incubation at room temperature, all extracts exerted potent in vitro hypocholesterolemic activities (100±0% reduction in cholesterol concentration). Performing GC-Ms analyses on the extracts revealed presence of 22 compounds in D. indusiata extract, while 29 compounds were detected in M. neogunnii extract, and 33 in H. erinaceus extract. Most of compounds were esters of fatty acids. Results in this study encourage using these mushrooms as functional foods, and highlight the need for conducting further in vivo studies to support their use in pharmaceutical industry.

SAT-456 Reduced Cholesterol Absorption and Synthesis Markers in Patients with Hyperthyroidism Due to Graves’ Disease

Background:Thyroid hormones have been reported to promote cell-surface expression of low-density lipoprotein receptor (LDL-R), and also increase mRNA expression of HMG-CoA reductase at the same time. Since LDL cholesterol (LDL-C) uptake via LDL-R is relatively superior to cholesterol synthesis in hyperthyroidism, plasma LDL-C levels can be lower as compared to euthyroid state. Conversely, hypothyroidism can increase plasma LDL-C levels because cholesterol absorption via Niemann-Pick C1-like 1 has been suggested to increase in hypothyroidism. However, there have been no reports about changes of cholesterol absorption and synthesis markers by the treatment of hyperthyroidism in patients with Graves’ disease. Patients and method: We collected plasma samples from patients with hyperthyroidism, who were diagnosed as Graves’ disease (n=17, M/F: 4/13, age: 24-70 years old). Thyroid hormones, general lipid profiles (Total cholesterol: TC, LDL-C, high-density lipoprotein cholesterol: HDL-C and triglyceride: TG), apolipoproteins, markers of cholesterol synthesis (lathosterol) and absorption (campesterol, sitosterol, cholestanol), lipoprotein lipase (LPL), and proprotein convertase subtilisin/kexin type 9 (PCSK9) were analyzed before treatment, and at euthyroid state (eu), 3 and 6 months after attaining euthyroid state (eu-3M and eu-6M). Result: It took 159.2±108.6 days to attain euthyroid state by the thiamazole treatment. TC, LDL-C and HDL-C levels were increased at eu (TC, 144.5±26.7 to 225.0±61.6; LDL-C, 77.8±20.9 to 138.9±43.9; HDL-C, 49.7±12.6 to 67.9±20.0 mg/dL: P<0.0001 vs before treatment, respectively). Such changes remained at eu-3M and eu-6M. TG was not changed at eu, but significantly increased at eu-6M (85.0±49.1 to 113.7±60.8 mg/dL, P=0.02). Cholesterol absorption markers were increased at eu, eu-3M and eu-6M (e.g. campesterol, 2.6±1.2 to 4.9±2.3; sitosterol, 1.5±0.6 to 2.9±1.4; cholestanol, 1.9±0.6 to 3.2±1.1 μg/mL: P<0.0001, eu vs before treatment, respectively). Cholesterol synthesis marker was increased at eu, eu-3M and eu-6M (e.g. lathosterol, 1.8±0.7 to 2.3±0.9 μg/mL: P=0.005, eu vs before treatment). Both LPL and PCSK9 were also increased at eu, eu-3M and eu-6M. Conclusion: These data suggest that both cholesterol absorption and synthesis are downregulated in patients with hyperthyroidism due to Graves’ disease and can be restored by attaining euthyroid state. In turn, LDL-C and TG levels should be carefully monitored during the treatment of Graves’ disease because hyperlipidemia could emerge in euthyroid state.

Fungal allergen-induced IL-33 secretion involves cholesterol-dependent, VDAC-1-mediated ATP release from the airway epithelium.

Alternaria aeroallergens induce the release of ATP from human bronchial epithelial (HBE) cells by activating a conductive pathway involving voltage-dependent anion channel-1 (VDAC-1) and by exocytosis of ATP localized within membrane vesicles. Inhibition of VDAC-1 blocked Alternaria-evoked Ca2+ uptake across the plasma membrane of HBE cells and interleukin (IL)-33 release into the extracellular media. Reducing cholesterol content with a cholesterol scavenger (β-methylcyclodextrin) or statin compound (simvastatin) blocked ATP and IL-33 release by lowering the expression of VDAC-1 in the plasma membrane. Pretreatment with simvastatin for 24h also inhibited the increase in tight junction macromolecule permeability that occurs following Alternaria exposure. These results establish a novel role for VDAC-1 as a mechanism underlying ATP release induced by fungal allergens and suggests a possible therapeutic use for cholesterol lowering compounds in reducing Alternaria-stimulated allergic inflammation. Human bronchial epithelial (HBE) cells exposed to allergens derived from the common saprophytic fungus, Alternaria alternata release ATP, which in turn stimulates P2X7 receptor-mediated Ca2+ uptake across the plasma membrane. The subsequent increase in intracellular calcium concentration induces proteolytic processing and secretion of interleukin (IL)-33, a critical cytokine involved in the initiation of allergic airway inflammation. A major objective of the present study was to identify the mechanism responsible for conductive ATP release. The results show that pretreatment of HBE cells with inhibitors of the voltage-dependent anion channel-1 (VDAC-1) or treatment with a VDAC-1selective blocking antibody or silencing mRNA expression of the channel by RNA interference, inhibit Alternaria-evoked ATP release. Moreover, inhibition of VDAC-1 channel activity or reducing protein expression blocked the secretion of IL-33. Similarly, reducing the cholesterol content of HBE cells with simvastatin or the cholesterol scavenger β-methylcyclodextrin also blocked ATP release and IL-33secretion by decreasing the level of VDAC-1 expression in the plasma membrane. In addition, simvastatin inhibited the increase in tight junction macromolecule permeability that was previously observed after Alternaria exposure. These results demonstrate a novel function for VDAC-1 as the conductive mechanism responsible for Alternaria-induced ATP release, an essential early step in the processing, mobilization and secretion of IL-33 by the airway epithelium. Furthermore, the simvastatin-evoked reduction of VDAC-1 expression in the plasma membrane, suggests the possibility that cholesterol lowering compounds may be beneficial in alleviating allergic airway inflammation induced by fungal allergens.

The Effect of Using Natural Feed Additive on Egg Production and Quality of Mojosari Duck (Anas plathyrhynchos)

The aim of this study was to determine the effect of using natural feed additives on egg production and quality of Mojosari Ducks. The animals used were 81-layer period Mojosari ducks 145 days old with an average egg weight 67.55 g and a coefficient diversity 8.98%. Each bird placed in experimental cages 2.25 x 2.25 m. Each plot (experimental unit) placed 3 ducks. The research treatment is adding feed additives (UB Feed) which are composed of natural ingredients, include amino acids, multivitamins, balanced micro minerals, acidifiers, probiotics, and phytobiotics. Research treatment was P1 (100% commercial complete feed), P2 (100% mixed feed), and P3 (100% mixed feed + 0.4% feed additive UB Feed). The research variables were egg production (percentage), cholesterol content (mg/100 mg) and protein content of egg yolk (g/100 g), and protein content of albumin (g/100 g). Based on the research results, the addition of natural feed additives had a very significant effect (P<0.01) on the egg production and quality of Mojosari duck eggs. The addition of natural additive feeds in feed increased egg production, yellow protein content and egg albumin and reduced cholesterol content of egg yolk.

Modification of the content of n-3 highly unsaturated fatty acid, chemical composition, and lipid nutritional indices in the meat of grass carp (Ctenopharyngodon idella) fed alfalfa (Medicago sativa) pellets.

A 120-d feeding trial was conducted to determine the effect of alfalfa (Medicago sativa) feeding on growth and chemical composition, fatty acid content, and nutritional and lipid indices of the meat of grass carp (Ctenopharyngodon idella). Two experimental diets were used: alfalfa pellet (AP) diet and artificial grain diet (GD). Final weight, feed conversion rate, and protein efficiency ratio were significantly greater in the GD group (P < 0.05). However, no differences in the length and condition factor were observed. The composition of the meat differed between treatments. The protein content was significantly greater in the AP group (P < 0.05), while the lipid and cholesterol contents were significantly greater in the GD group (P < 0.05). A greater proportion of saturated, n-6 polyunsaturated, and n-6 highly unsaturated fatty acids was obtained in the GD group. The AP group accumulated a greater concentration of eicosapentaenoic (EPA), docosapentaenoic (DPA), and docosahexaenoic (DHA) acids (P < 0.05). The fatty acid composition of the meat determined a significant decrease in the thrombogenicity index and saturation index (S/P) in the AP group (P < 0.05). The Elongase index was greater in the GD group (P < 0.05). In contrast, the AP group had a greater index of Δ9 Desaturase and Δ5 + Δ6 Desaturase for n-3 and n-6 fatty acids (P < 0.05). These results suggest that alfalfa feeding decreases the growth of C. idella but improves the quality of meat by increasing the protein, EPA, and DHA contents. It also reduces cholesterol content and improves nutritional indices.

Phytosterol vehicles used in a functional product modify carotenoid/cholesterol bioaccessibility and uptake by Caco-2 cells

Abstract Functional foods containing dispersible phytosterols (DPs) are recommended to reduce cholesterol absorption in humans. However, only a few studies have been conducted on the effect of DP vehicles on carotenoid bioaccessibility and uptake by intestinal cells. On a previously developed fermented maize product containing both DPs and carotenoids, we aim to evaluate the effect of DPs encapsulated by maltodextrin on the carotenoid/phytosterol/cholesterol interactions during gastro-duodenal digestion. Thanks to maltodextrin properties, β-carotene and lycopene bioaccessibilities were significantly improved by 40.2 ± 1.4% while that of β-cryptoxanthin decreased by 14 ± 0.1%. Additionally, the presence of DPs reduced the cholesterol micellarization by 51.8 ± 4.2%. Despite a slight decrease in carotenoid uptake caused by the DP vehicle, related to micelle size, an inhibition of cholesterol accumulation by Caco-2 cells was observed. These results highlighted the key role of maltodextrin as a vehicle of DPs on carotenoid and cholesterol absorption.

Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 μg/mL) and 25-hydroxycholesterol (2 μg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 μM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.

Insights into the in-vitro hypocholesterolemic, antioxidant, antirotavirus, and anticolon cancer activities of the methanolic extracts of a Japanese lichen, Candelariella vitellina, and a Japanese mushroom, Ganoderma applanatum

Background and objective Medicinal mushrooms, as well as lichens are potential sources of bioactive compounds against many lethal diseases. Therefore, in-vitro evaluations of the biological activities of the 80% methanolic extracts of two Japanese originated samples, namely, the mushroom Ganoderma applanatum, and the lichen Candelariella vitellina have been performed. Materials and methods Extraction of C. vitellina and G. applanatum was conducted using 80% methanol. The resulted extracts were examined for their in-vitro hypocholesterolemic and antirotavirus activities, as well as antihuman colon cancer action. Results and conclusion It was revealed that both extracts have potent hypocholesterolemic effects. G. applanatum in concentration of 24 mg/ml could successfully reduce the cholesterol concentration to 100±0% after 96 h of incubation at room temperature, whereas reaching this degree of reduction in cholesterol concentration required using 32 mg/ml of C. vitellina extract. On the contrary, the extract of C. vitellina at concentration of 1.0 mg/ml exhibited a stronger DPPH scavenging activity (99.5±0.166%), in comparison with 66.24±0.43% in case of using the same concentration of the G. applanatum extract. C. vitellina extract showed antirotavirus in a therapeutic index of 11, whereas G. applanatum extract recorded 3.4 only. The antihuman colon cancer study elucidated that both extracts have a moderate activity toward HCT116 human colon carcinoma. C. vitellina extract achieved a cytotoxicity of 57.90±4.4%, whereas the extract of G. applanatum displayed only 43.10±0.9%. Studies on G. applanatum and C. vitellina introduce them as promising sources of biologically potent compounds that can be candidates for use in treatment of many diseases after further studies.

Effect of Hevea brasiliensis seed meal or Euphorbia heterophylla seed supplemented diets on performance, physicochemical and sensory properties of eggs, and egg yolk fatty acid profile in guinea fowl (Numida meleagris)

A total of 144 French selected breed (Galor) female guinea fowl (GF) of 42 wk of age were enrolled for a feeding trial of 15, 30, and 45 D duration. The birds were randomly assigned to 18 cages, each containing 8 birds. A total of 3 isonitrogenous and isocaloric dietary treatments were trialed, each diet comprising 6 replications (cages), which meant a total of 48 birds per diet. The GF were fed either a control diet C (commercial diet “FACI ponte 20”, SIPRA, Ivory Coast, usually used for all poultry species) or the diet C supplemented with 5% Euphorbia heterophylla seeds (diet E) and the diet C supplemented with 5% Hevea seed meal (Hevea brasiliensis) (diet H). Animal performance were assessed for 3 periods (days 0 to 15, 0 to 30, and 0 to 45), and egg quality and composition were assessed at 15, 30, and 45 D of the trial. The results indicated no mortality during the trial. The laying rate was the highest (43.9%) with diet E and the lowest with diet C (32.5%), the laying rate with diet H being intermediate (38.5%). Diet E containing Euphorbia seeds led to a reduced cholesterol content of the eggs. Additionally, inclusion of Euphorbia seeds and, to a lesser extent, of the Hevea seed meal in the diet led to n-3 polyunsaturated fatty acid enriched GF eggs, with thereby, improved nutritional value. A sensory test did not find any difference between the 3 diets on trial.

Identification of a novel cholesterol-lowering dipeptide, phenylalanine-proline (FP), and its down-regulation of intestinal ABCA1 in hypercholesterolemic rats and Caco-2 cells

There has been no report about in vivo active cholesterol-lowering dipeptide in any protein origin, despite their potential health benefits. Cattle heart protein hydrolysate ultra-filtrate (HPHU, molecular weight < ca. 1,000 Da peptide mixture) exhibits cholesterol-lowering activity in hypercholesterolemic rats, but the active peptide in HPHU that lowers serum cholesterol levels and its molecular mechanism are unknown. In this study, we separated and purified HPHU to identify a novel cholesterol-lowering dipeptide (phenylalanine-proline, FP) and characterized the mechanism underlying its effects in vivo and in vitro. We identified FP as an active peptide from HPHU by MALDI-TOF mass spectrometry. FP significantly decreased serum total and non-HDL cholesterol and hepatic cholesterol levels in rats. FP significantly increased serum HDL cholesterol, accompanied by a significant decrease in the atherogenic index. FP also significantly increased fecal cholesterol and acidic steroid excretion. Moreover, FP significantly decreased ATP-binding cassette transporter A1 (ABCA1) expression in the rat jejunum and reduced cholesterol absorption in Caco-2 cells. We found a novel cholesterol-lowering dipeptide FP that could improve cholesterol metabolism via the down-regulation of intestinal ABCA1. The cholesterol-lowering action induced by FP was disappeared in PepT1KO mice. FP-induced cholesterol-lowering action is mediated via PepT1 in mice.

Stroke-prone spontaneously hypertensive rats have reduced hydroxysteroid 17-β dehydrogenase 7 levels for low cholesterol biosynthesis.

Reduced serum cholesterol content was recently reported to be one of the factors responsible for cerebral haemorrhage. Stroke-prone spontaneously hypertensive rats (SHRSP) are known to have lower serum cholesterol content than normotensive Wistar-Kyoto rats (WKY). We previously reported that lower levels of mevalonate pyrophosphate decarboxylase (MPD) and squalene epoxidase (SQE), which are associated with cholesterol biosynthesis in the liver, are involved in the low serum cholesterol content in SHRSP. Here, we investigate the levels of sterol 14-demethylase (CYP51), methylsterol monooxygenase (SC4MOL), and hydroxysteroid 17-β dehydrogenase 7 (HSD17B7), which contribute to the cholesterol synthesis pathway in the conversion of lanosterol to zymosterol, in SHRSP and WKY. The HSD17B7 mRNA levels in the liver of SHRSP were markedly lower than those in WKY, whereas no significant differences were observed in CYP51 and SC4MOL levels in the two types of rats. The relative levels of protein, heteronuclear RNA, and mRNA of HSD17B7 were also significantly lower in SHRSP than in WKY. The degradation rates of HSD17B7 were the same in SHRSP and WKY. The protein levels of HSD17B7 were not significantly reduced in tissues other than the liver, including the brain, lung, heart, spleen, kidney, and testis, in SHRSP. Moreover, HSD17B7 activity was significantly lower in SHRSP than in WKY. Thus, our results indicated that low protein levels and activity of HSD17B7 are responsible for the reduced cholesterol content in SHRSP, indicating that HSD17B7, along with MPD and SQE, is involved in the decreased cholesterol synthesis in the liver of SHRSP.