Cholesterol-lowering Effect Research Articles

Abstract 325: The Regulation of Endothelial Function Through Hmgcr/mevalonate Pathway Mediated Yap Activity

Background: Cardiovascular diseases (CVD) are the leading cause of death in the United States. Statins, a class of hydroxy-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors, have been proven to be effectively prevent and treat CVD by improving vascular functions independent of their cholesterol-lowering effect. However, the molecular mechanisms by which statins improve cardiovascular functions remain elusive. In this study, we used human induced pluripotent stem cells-derived endothelial cells (hiPSC-ECs) to explore the protective role of statins in the vascular system. Methods and Results: hiPSCs were generated from 3 healthy individuals and differentiated into endothelial cells using two different iPSC clones and two batches (4 biological replicates for each individual). hiPSC-ECs of each individual were treated with simvastatin or a vehicle control. The RNA-sequencing analysis was performed on 12 control and 12 statin-treated hiPSC-ECs. A total number of 2,580 differentially expressed genes (DEGs) were found in simvastatin-treated hiPSC-ECs. Gene enrichment analysis revealed that statin-upregulated DEGs were highly enriched in angiogenesis and anti-inflammation pathways. Interestingly, statin-downregulated DEGs were significantly enriched in epigenetic regulation and nucleosome assembly pathways, suggesting an epigenetic regulatory role of stains in vascular gene expression. To test this hypothesis, we further performed the Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) analysis on vehicle or simvastatin treated hiPSC-ECs. Transcription factor (TF) binding motif analyses of ATAC-seq peaks using HOMER revealed that YAP/TEAD binding was the most significantly downregulated TF after statin treatment. Furthermore, we observed that statin can improve endothelial functions (e.g., angiogenesis and nitric oxide production) after the YAP activity was inhibited. The ChIP-seq analysis showed that statin downregulated the expression levels of genes associated with the endothelial-to-mesenchymal transition (EndoMT) by attenuating the binding capacity of YAP. As such, simvastatin effectively rescued diabetic vascular dysfunction mainly through inhibiting EndoMT. Conclusion: We found that statins can improve endothelial functions through attenuating the chromatin accessibility of EndoMT-related genes, a process tightly regulated by the activity of YAP. These findings will provide novel insights into the protective mechanisms of statins in the cardiovascular system beyond their cholesterol-lowering effects.

Consumption of Wild Rice (Zizania latifolia) Prevents Metabolic Associated Fatty Liver Disease through the Modulation of the Gut Microbiota in Mice Model.

Metabolic associated fatty liver disease (MAFLD) due to excess weight and obesity threatens public health worldwide. Gut microbiota dysbiosis contributes to obesity and related diseases. The cholesterol-lowering, anti-inflammatory, and antioxidant effects of wild rice have been reported in several studies; however, whether it has beneficial effects on the gut microbiota is unknown. Here, we show that wild rice reduces body weight, liver steatosis, and low-grade inflammation, and improves insulin resistance in high-fat diet (HFD)-fed mice. High-throughput 16S rRNA pyrosequencing demonstrated that wild rice treatment significantly changed the gut microbiota composition in mice fed an HFD. The richness and diversity of the gut microbiota were notably decreased upon wild rice consumption. Compared with a normal chow diet (NCD), HFD feeding altered 117 operational taxonomic units (OTUs), and wild rice supplementation reversed 90 OTUs to the configuration in the NCD group. Overall, our results suggest that wild rice may be used as a probiotic agent to reverse HFD-induced MAFLD through the modulation of the gut microbiota.

Successful pharmacological management of a child with compound heterozygous familial hypercholesterolemia and review of the recent literature

Severe familial hypercholesterolemia (SFH) is characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) and severe early-onset cardiovascular disease if left untreated. We report on the decade-long therapeutic journey of a 15-year-old boy with SFH due to a severe compound heterozygous genotype. He presented at the age of 5 years with widespread xanthomas and LDL-C of 17.4 mmol/L. He was diagnosed with SFH, initially treated with colestyramine that was subsequently combined with simvastatin. At the age of 12 years, he was diagnosed to have supravalvular aortic stenosis and ezetimibe/atorvastatin was introduced in place of colestyramine/simvastatin. At the age of 14 years, he received triple therapy with evolocumab, initially at the recommended dose of 420 mg monthly and then reduced to 140 mg biweekly. Currently at the age of 15 years, he is on atorvastatin 40 mg ON, ezetimibe 10 mg OM, and evolocumab 140 mg biweekly, achieving LDL-C levels of 2.4 mmol/L. Genetic testing identified compound heterozygous mutations in the LDL receptor genes [c.(940 + 1_941-1) (1845 + 1_1846-1)dup] and exon 12, nucleotide c.1747 C > T, amino acid p.(His583Tyr). Medical management without lipoprotein apheresis can achieve target LDL-C in children with SFH. Our patient, who developed supravalvular aortic stenosis at the age of 12 years, needed early aggressive treatment when SFH guidelines and newer drugs for young children were unavailable. Our patient demonstrated that 140 mg biweekly of evolocumab has the same cholesterol-lowering effect as the recommended 420 mg monthly dose.

Phytosterol supplements do not inhibit dipeptidyl peptidase-4

Background and aimsSeveral commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their potential anti-hyperglycaemic effects. This study aimed to evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitory effects of phytosterol supplements in silico and in vitro to determine their potential for anti-diabetic activity. MethodsDocking studies were carried out in silico to evaluate the potential for interactions between three major phytosterol compounds (stigmasterol, β-sitosterol, campesterol) and the DPP-4 enzyme, the enzyme that is inhibited by the anti-diabetic gliptins. Gas chromatography–tandem mass spectrometry (GC-MS/MS) was used to analyse three different supplements for phytosterol content. DPP-4 inhibitory activity was tested in vitro for these phytosterol supplements and two major phytosterol standards. ResultsIn silico calculations predicted free binding energies for DPP-4 with the phytosterols to be: stigmasterol −8.78 kcal/mol; β-sitosterol −8.70 kcal/mol; campesterol −8.40 kcal/mol. These binding energies indicated a potential for significant DPP-4 inhibition. However, these results were not supported by the in vitro studies. Stigmasterol and β-sitosterol had an IC50 > 50 mg/ml (maximum tested concentration) and the Thompson’s Cholesterol Manager® and Mega Strength Beta Sitosterol® supplements gave an IC50 > 100 mg/ml (maximum tested concentration). Blackmores Cholesterol Health® gave an IC50 value of 40 mg/ml which was attributed to β-carotene content. ConclusionsPhytosterol supplements do not appear to offer any anti-diabetic activity potential via pathways that involve the inhibition of DPP-4.

Effect of chitosan on plasma lipids, hepatic lipids, and fecal bile acid in hamsters

Chitosan is a natural product derived from chitin that possesses hypocholesterolemic properties. However, the mechanism of its cholesterol-lowering effect is still unclear. This study was designed to investigate the effect of chitosan on plasma lipoprotein cholesterol, liver cholesterol and fecal excretion of cholesterol and bile acid in hamsters. Hamsters were fed a high-cholesterol (0.2%) diet containing 4% cellulose (CE) or 4% chitosan (CS) for eight weeks. The hamsters fed the CS diet had significantly lowered plasma total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) than those fed the CE diet. CS had no effect on high-density lipoprotein cholesterol (HDL-C) level, but higher ratio of HDL-C to TC was observed in hamsters fed the CS diet when compared with those fed with the CE diet. In addition, CS did not change plasma triglyceride and cholesteryl ester transfer protein (CETP) activity. Hepatic cholesterol contents were significantly lower in hamsters fed CS primarily due to the reduced accumulation of the esterified cholesterol. Fecal excretion of cholesterol and bile acid were significantly increased in hamsters after the CS treatment. Results from this study suggest that the cholesterol-lowering effect of CS may be primarily related to an increase in fecal excretion of cholesterol and bile acid in hamsters.

The cholesterol-lowering effect of unripe Rubus coreanus is associated with decreased oxidized LDL and apolipoprotein B levels in subjects with borderline-high cholesterol levels: a randomized controlled trial

BackgroundRubus coreanus (R. coreanus) possesses properties that may decrease cholesterol levels.MethodsThe effects of unripe R. coreanus (uRC) consumption on low-density lipoprotein (LDL) and total cholesterol levels related to decreased circulating apolipoprotein (Apo) B and oxidized LDL levels were evaluated. This randomized, double-blind, placebo-controlled study included subjects with borderline-high cholesterol levels (between 200 and 239 mg/dL) who consumed one capsule daily containing 600 mg of freeze-dried uRC extract (n = 39) or the placebo (n = 38).ResultsAfter 12 weeks, the uRC group showed reductions of 21.23 ± 4.36 mg/dL in total cholesterol levels (P = 0.007) and 15.61 ± 4.16 mg/dL in LDL cholesterol levels (P = 0.032). In addition, significantly greater reductions in Apo B levels were observed in the uRC group (− 3.48 ± 3.40 mg/dL), but Apo B levels were increased in the placebo group (6.21 ± 2.84 mg/dL; P = 0.032). Furthermore, a remarkably lower oxidized LDL level was detected in the uRC group (57.76 ± 2.07 U/L) than in the placebo group (66.09 ± 3.47 U/L) after 12 weeks of consumption (P = 0.044).ConclusionsBecause of its cholesterol-lowering effect, uRC shows great promise as a therapeutic agent for subjects with borderline-high total blood cholesterol levels.Trial registrationClinicalTrials.gov Identifier: NCT03649620 (8/28/2018, retrospectively registered).

Effects of a novel nutraceutical combination (BruMeChol\u2122) in subjects with mild hypercholesterolemia: study protocol of a randomized, double-blind, controlled trial

BackgroundElevated cholesterol levels and systemic inflammation are considered relevant risk factors for cardiovascular disease (CVD) development and progression. Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol™, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia.MethodsThe study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12 weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age ≥ 40 years) with mild hypercholesterolemia (total serum cholesterol levels ≥ 200 and ≤ 250 mg/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15 min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (Citrus bergamia), flavonoid-rich extract of olive fruit (Olea europaea), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12 weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study.DiscussionThis protocol study, planned to verify the effects of BruMeChol™ dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12619000170123. Retrospectively registered on 5 February 2019

Effects of Lactobacillus paragasseri Y20 on cholesterol-lowering, intestinal microbiota and liver metabolism in rats with hypercholesterolaemia

To evaluate the cholesterol-lowering effects of Lactobacillus paragasseri Y20 on rats with high cholesterol diet and its effect on the gut microbiota of rats, and to explore the potential mechanism of Lactobacillus paragasseri regulating hypercholesterolemia in rats. Thirty rats were randomly divided into three groups and were treated with normal diet, high cholesterol diet+PBS, and high cholesterol diet+Lactobacillus paragasseri Y20, respectively. After five consecutive weeks of treatment, serum lipids were measured by ELISA. Rat feces were collected and DNA was extracted for 16 S rRNA amplicon sequencing analysis. Rat livers were collected and analyzed for non-targeted metabolites using high performance liquid chromatography. Compared with the high-cholesterol model group, Lactobacillus paragasseri Y20 treatment could reduce the serum triglyceride and low-density lipoprotein concentrations and increase the high-density lipoprotein concentration in rats. High-cholesterol diet decreased the intestinal flora diversity and richness of rats, while Y20 intervention can effectively restore the change of intestinal flora of high-cholesterol rats. High cholesterol dietsmainly caused the changes in the relative abundance in phylum of Firmicutes, Deferribacteres, Verrucomicrobia, and Proteobacteria, increasing Akkermansia, Clostridium_III, and Clostridium_XIVbgenera, and decreasing the intestinimonasgenus. However, Y20 intervention restored the diversity of gut microbiota and alteration in relative abundance of these bacteria caused by high-cholesterol diet. Y20 could effectively decrease the higher relative abundance of Akkermansiahigh-cholesterol diet. Lactobacillus paragasseri Y20 can alleviate hypercholesterolemia in rats, regulate the gut microbiotadiversity and composition and affect liver metabolism in hypercholesterol rats.

Berberine Nanoencapsulation Attenuates Hallmarks of Scoplomine Induced Alzheimer's-Like Disease in Rats.

Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, anti-inflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-Nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. BBR-NPs were formulated using the ionic gelation method, and tripolyphosphate was chosen as a crosslinker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty-six Wistar male rats were randomly distributed into three control groups, received saline, polyethylene glycol or Chitosan- NPs, respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates, as well as neuroplasticity markers and histopathological examination were assessed. Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands towards AChE and Aβ42 formation and significantly down-regulated Tau, iNOS and BACE gene expression in rats' hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake, which need more investigation in future work.

The potential cholesterol-lowering and prebiotic effects of bamboo shoot dietary fibers and their structural characteristics.

The physicochemical and physiological properties of soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) from bamboo shoots were investigated in present study. IDF showed better adsorption capacity than the corresponding SDF from the same species. Microstructure observation results indicated that the surface of IDF was porous, whereas the SDF was relatively flat and compact. The cholesterol-adsorption capacities of IDF and SDF from Fargesia spathacea were relatively higher than the other species. Both SDF and IDF from F. spathacea showed potential prebiotic effects, although the Lactobacillus and Bifidobacterium promotion effects of SDF were relatively stronger than IDF. Compared with control, the concentration of total short chain fatty acids in IDF and SDF supplement groups were increased by 1.28 and 0.71 folds, respectively. These results suggested that F. spathacea dietary fibers with strong cholesterol-adsorption activity and prebiotic potential, could be used as a bioactive ingredient in functional foods production.

Association of Dietary Phytosterols with Cardiovascular Disease Biomarkers in Humans.

Cardiovascular disease (CVD) is a leading cause of death worldwide. Elevated concentrations of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are major lipid biomarkers that contribute to the risk of CVD. Phytosterols well known for their cholesterol-lowering ability, are non-nutritive compounds that are naturally found in plant-based foods and can be classified into plant sterols and plant stanols. Numerous clinical trials demonstrated that 2 g phytosterols per day have LDL-C lowering efficacy ranges of 8-10%. Some observational studies also showed an inverse association between phytosterols and LDL-C reduction. Beyond the cholesterol-lowering beneficial effects of phytosterols, the association of phytosterols with CVD risk events such as coronary artery disease and premature atherosclerosis in sitosterolemia patients have also been reported. Furthermore, there is an increasing demand to determine the association of circulating phytosterols with vascular health biomarkers such as arterial stiffness biomarkers. Therefore, this review aims to examine the ability of phytosterols for CVD risk prevention by reviewing the current data that looks at the association between dietary phytosterols intake and serum lipid biomarkers, and the impact of circulating phytosterols level on vascular health biomarkers. The clinical studies in which the impact of phytosterols on vascular function is investigated show minor but beneficial phytosterols effects over vascular health. The aforementioned vascular health biomarkers are pulse wave velocity, augmentation index, and arterial blood pressure. The current review will serve to begin to address the research gap that exists between the association of dietary phytosterols with CVD risk biomarkers.

Bioactive Components of Milk Fat Globule Membrane and Technological Applications

The membrane contained in milk and surrounding the milk fat spheres represents a nutraceutical matrix in a unique biophysical system called the milk fat globule membrane or membrane (MFGM). In recent years, the identification of the various health-beneficial components of MFGM has been evaluated as a food ingredient with bioactive properties, while increasing the interest in the development of functional products as well as efforts to improve the technological properties of foods. MFGM switches to buttermilk during butter production. Buttermilk is rich in phospholipid and bioactive peptide content and draws attention with its emulsification effect in foods. In addition, MFGM compounds also have an anticarcinogenic, antibacterial, blood pressure and cholesterol-lowering effect, anti-oxidative stress and cardiovascular discomfort, as well as regulating the immune system. With its stated positive effects, this membrane material enables the development of new nutraceutical foods. Keywords: Milk Fat Gobule Membrane, Bioactive Component, Nutraceutical, Buttermilk. DOI: 10.7176/JSTR/6-08-02

Probiotic characterization and in vitro cholesterol lowering effects of lactic acid bacteria isolated from healthy Thai infants

Probiotic characterization and in vitro cholesterol lowering effects of lactic acid bacteria isolated from healthy Thai infants

Impact of the Gut Microbiota on Atorvastatin Mediated Effects on Blood Lipids.

Background and Aims: The mechanisms of interindividual variation of lipid regulation by statins, such as the low-density lipoprotein cholesterol (LDL) lowering effects, are not fully understood yet. Here, we used a gut microbiota depleted mouse model to investigate the relation between the gut microbiota and the regulatory property of atorvastatin on blood lipids. Methods: Mice (C57BL/6) with intact gut microbiota or antibiotic induced abiotic mice (ABS) were put on standard chow diet (SCD) or high fat diet (HFD) for six weeks. Atorvastatin (10 mg/kg body weight/day) or a control vehicle were applied per gavage for the last four weeks of dietary treatment. Blood lipids including total cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein and sphingolipids were measured to probe microbiota-dependent effects of atorvastatin. The expression of genes involved in hepatic and intestinal cholesterol metabolism was analyzed with qRT-PCR. The alteration of the microbiota profile was examined using 16S rRNA qPCR in mice with intact gut microbiota. Results: HFD feeding significantly increased total blood cholesterol and LDL levels, as compared to SCD in both mice with intact and depleted gut microbiota. The cholesterol lowering effect of atorvastatin was significantly attenuated in mice with depleted gut microbiota. Moreover, we observed a global shift in the abundance of several sphingolipids upon atorvastatin treatment which was absent in gut microbiota depleted mice. The regulatory effect of atorvastatin on the expression of distinct hepatic and intestinal cholesterol-regulating genes, including Ldlr, Srebp2 and Npc1l1 was altered upon depletion of gut microbiota. In response to HFD feeding, the relative abundance of the bacterial phyla Bacteroidetes decreased, while the abundance of Firmicutes increased. The altered ratio between Firmicutes to Bacteroidetes was partly reversed in HFD fed mice treated with atorvastatin. Conclusions: Our findings support a regulatory impact of atorvastatin on the gut microbial profile and, in turn, demonstrate a crucial role of the gut microbiome for atorvastatin-related effects on blood lipids. These results provide novel insights into potential microbiota-dependent mechanisms of lipid regulation by statins, which may account for variable response to statin treatment.

Evaluation of lipid and cholesterol-lowering effect of bioflavonoids from bergamot extract

Several natural products have been reported to be involved in the suppression of adipogenesis. In this study, we reveal that a bergamot extract (BE) decreased the accumulation of intracellular lipids in murine pre-adipocytes 3T3-L1 cells during adipogenic differentiation. Both the inhibition of HMG-CoA reductase activity and the differentiation and proliferation of adipocytes could be used as a strategy for the treatment and prevention of obesity. The results of this study show a reduction of HMG-CoA activity and of lipid droplet accumulation in the presence of the BE, suggesting the potential of BE as an anti-adipogenic agent to lower the content of cholesterol and body fat and prevent a gain in body weight. Moreover, BE as the result of high percentages of flavonoid compounds such as neoriocitrin, naringin and neohesperidin, the main flavonoids contained in BE, led to significant inhibition of DPPH free radical, demonstrating a strong radical scavenging activity.

Mulberry Fruit Extract Promotes Serum HDL-Cholesterol Levels and Suppresses Hepatic microRNA-33 Expression in Rats Fed High Cholesterol/Cholic Acid Diet.

Serum high-density lipoprotein cholesterol (HDL-C) levels and cholesterol excretion are closely associated with the risk of cardiovascular complications. The specific aim of the present study was to investigate the cholesterol lowering effect of mulberry fruit in rats fed a high cholesterol/cholic acid diet. Four-week supplementation with mulberry fruit extract significantly decreased serum and hepatic cholesterol (TC), serum low-density lipoprotein cholesterol (LDL-C), and fecal bile acid levels without changes in body weight and food intake (p < 0.05). Mulberry fruit extract significantly inhibited hepatic sterol-regulatory element binding protein (Srebp) 2 gene expression and upregulated hepatic mRNA levels of liver X receptor alpha (Lxr-α), ATP-binding cassette transporter 5 (Abcg5), and cholesterol 7 alpha-hydroxylase (Cyp7a1), which are involved in hepatic bile acid synthesis and cholesterol metabolism (p < 0.05). In addition, hepatic microRNA-33 expression was significantly inhibited by supplementation of mulberry fruit extract (p < 0.05). These results suggest the involvement of miR-33, its associated hepatic bile acid synthesis, HDL formation, and cholesterol metabolism in mulberry fruit-mediated beneficial effects on serum and hepatic lipid abnormalities.

Inhibitory Effect of Calcium Alginate on Postprandial Blood Glucose Elevation: Basic and Clinical Studies

Diabetes is known to increase the risk of myocardial and cerebral infarction, as well as complications such as retinopathy, nephropathy and neuropathy. It is important for diabetics to improve their eating habits, for example, by eating slowly, avoiding overeating, and increasing their intake of vegetables, in order to suppress sudden rises in blood glucose (Glu) levels. On the other hand, alginic acid (Alg), which is a polysaccharide derived from brown algae, is used as a food and medicinal additive, a health food and a pharmaceutical, based on its blood cholesterol-lowering effect and protective effect on the gastric mucosa. It was recently reported that calcium alginate (Ca-Alg) has the pharmacological effect of suppressing blood Glu elevation. We investigated the mechanism of this effect and found that Ca-Alg inhibits the metabolism of starch in the gastrointestinal tract by inhibiting the activity of α-glucosidase, which degrades maltose into Glu.We also examined the influence of the amount of Ca-Alg added to the diet and the particle size of the Ca-Alg on postprandial blood Glu elevation in rats. Subsequently, we conducted several clinical trials. We asked healthy adults to eat udon noodles, soba (buckwheat noodles), and Chinese noodles containing CaAlg, and measured the blood Glu levels after consumption. In each case, Ca-Alg decreased blood Glu levels and suppressed total absorption of Glu. This review summarizes the results of our basic and clinical studies on the effects of Ca-Alg on postprandial blood Glu elevation.

Hepatic Lipidomics Analysis Reveals the Antiobesity and Cholesterol-Lowering Effects of Tangeretin in High-Fat Diet-Fed Rats.

Tangeretin (TAN) exhibited antilipogenic, antidiabetic, and lipid-lowering effects. However, the lipid biomarkers and the underlying mechanisms for antiobesity and cholesterol-lowering effects of TAN have not been sufficiently investigated. Herein, we integrated biochemical analysis with lipidomics to elucidate its efficacy and mechanisms in high-fat diet-fed rats. TAN at supplementation levels of 0.04 and 0.08% not only significantly decreased body weight gain, serum total cholesterol, and low-density lipoprotein cholesterol levels but also ameliorated hepatic steatosis. These beneficial effects were associated with the declining levels of fatty acids, diacylglycerols (DGs), triacylglycerols, ceramides, and cholesteryl esters by hepatic lipidomics analysis, which were attributed to downregulating lipogenesis-related genes and upregulating lipid oxidation- and bile acid biosynthesis-related genes. Additionally, 21 lipids were identified as potential lipid biomarkers, such as DGs and phosphatidylethanolamines. These findings indicated that the modulation of lipid homeostasis might be the key pathways for the mechanisms of TAN in the antiobesity and cholesterol-lowering effects.

Effects of Policosanol in Patients With Metabolic Syndrome: A Six-Month Study

Background: The metabolic syndrome comprises a set of cardiovascular risk factors represented by obesity of central distribution, dyslipidemias, glucose metabolism abnormalities and arterial hypertension, closely associated with insulin resistance. Policosanol is a mixture of high molecular weight alcohols purified from sugar cane wax with cholesterol-lowering and antioxidant effects. The aim of this study is to investigate in the medium term the effects of policosanol in patients with metabolic syndrome, as well as its safety and tolerability. Methods: This phase IV study had a double-blind, randomized and controlled design, with two parallel groups that received policosanol (10 mg/day) or placebo for 6 months. The study included patients with metabolic syndrome, of both sexes, aged between 25 and 70 years. As a primary efficacy variable, the effects on oxidative stress were evaluated, while the effects on lipids profile variables were considered as a secondary efficacy variable. Statistical analysis of the data was performed according to the intention-to-treat method. Results: The study included 100 patients with metabolic syndrome (81 men, 19 women) (average age: 51 years). At the end of 6 months of treatment, policosanol significantly reduced the redox index with respect to the initial values and with respect to the placebo group. Policosanol significantly reduced levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C), as well as increased serum levels of high-density lipoprotein cholesterol (HDL-C), while triglyceride levels although reduced at the end of treatment, this reduction was not significant. The policosanol was safe and well tolerate; it did not affect the physical and laboratory parameters investigated, with the exception of a significant and favorable reduction in the levels of apolipoprotein (Apo) B. Conclusions: It is concluded that policosanol therapy for 6 months produces improvements on oxidative stress in patients with metabolic syndrome, in addition to a beneficial effect on their lipid profile, being safe and well tolerated. J Endocrinol Metab. 2020;10(2):36-44 doi: https://doi.org/10.14740/jem642

Complete Genome Sequence of Lactobacillus plantarum EM, A Putative Probiotic Strain with the Cholesterol-Lowering Effect and Antimicrobial Activity.

Lactobacillus plantarum EM is a probiotic strain with antimicrobial activity, cholesterol-lowering effects, and tolerance to acid and bile. To understand the genetic basis of the probiotic characteristics of this strain, genome sequencing and probiotic-related genetic analysis were performed. The genomic characteristics of L. plantarum EM were confirmed by comparative genomic analysis with 41 probiotic lactic acid bacteria, including 10 L. plantarum strains. L. plantarum EM was shown to contain a circular chromosome of 3,184,808bp and eight plasmids with various lengths from 5,027 to 76,369bp. The L. plantarum EM genome had a total of 3560 protein-coding genes, including probiotic-related genes, such as tolerance to acid and bile, temperature stress, and oxidative stress. Comparative genomic analysis showed that L. plantarum EM contained plantaricin and bovicin gene clusters, which are related to antimicrobial activity, and five bile salt hydrolase genes related to serum cholesterol-lowering effects. The genomic analysis confirmed the probiotic properties of L. plantarum EM, and our results indicated that this strain has potential application for use as an industrially important probiotic.