Reduce Blood Lipid Levels Research Articles

Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer\u2019s disease

ObjectiveAlzheimer’s disease (AD) is a global health problem without effective methods to alleviate the disease progression. Amyloid β-protein (Aβ) is widely accepted as a key biomarker for AD. Metabolic syndromes, including obesity and insulin resistance, are key high risk factors for AD. Akkermansia muciniphila (Akk), the only representative human gut microbe in the genus Verrucomicrobia, can prevent the weight gain caused by a high-fat diet, repair the damaged integrity of the intestinal epithelium barrier, reduce endotoxin levels in blood and improve insulin resistance. The aim of this study is to explore the impact of Akk administration in AD model mice in different diets.MethodsAPP/PS1 mice were fed either a normal chow diet or a high-fat diet and were treated with Akk by gavage each day for 6 months. The impacts of Akk on glucose metabolism, intestinal barrier and lipid metabolism in the mouse model of AD were determined. Changes in brain pathology and neuroethology were also analyzed.ResultsAkk effectively reduced the fasting blood glucose and serum diamine oxidase levels, and alleviated the reduction of colonic mucus cells in APP/PS1 mice. After treatment with Akk, the APP/PS1 mice showed obviously reduced blood lipid levels, improved hepatic steatosis and scapular brown fat whitening. Moreover, Akk promoted the reduction of Aβ 40–42 levels in the cerebral cortex of APP/PS1 mice, shortened the study time and improved the completion rate in Y-maze tests.ConclusionAkk effectively improved glucose tolerance, intestine barrier dysfunction and dyslipidemia in AD model mice. Our study results suggested that Akk could delay the pathological changes in the brain and relieve impairment of spatial learning and memory in AD model mice, which provides a new strategy for prevention and treatment of AD.

Application of aerobic training combined with auricular point pressing in reducing blood glucose and lipid levels in patients with carotid atherosclerosis

Objective To explore the effect of aerobic training combined with auricular acupoint pressing on improving blood glucose and lipid levels in patients with carotid atherosclerosis. Methods A total of 200 patients diagnosed with atherosclerosis in the hospital from January to December 2017 were selected. According to the random number table, the patients were divided into observation group and control group, with 100 patients each.The control group received daily life guidance after diagnosis, and the observation group received aerobic training combined with auricular point pressing on the basis of the control group. The intervention time was 6 months.Carotid intima-media thickness (IMT), body mass (BMI), waist-to-hip ratio (WHR), blood glucose and lipid levels were compared between the two groups before and after intervention. Results After intervention, IMT, BMI and WHR levels in the observation group were significantly lower than those in the control group, with statistically significant differences(P<0.05). The levels of fasting blood glucose (FPG), 2 hours postprandial blood glucose (2hFPG), Hemoglobin A1c(HBA1c), total serum cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the observation group were significantly lower than those in the control group after intervention, with statistically significant differences(P<0.05). The incidence of coronary heart disease and stroke in the observation group was significantly lower than that in the control group during the 1-year follow-up, and the differences were statistically significant(P<0.05). Conclusions Aerobic training combined with auricular acupoint pressing can effectively control the blood glucose and blood lipid levels in patients with atherosclerosis, and effectively prevent the occurrence of cardiovascular and cerebrovascular diseases. Key words: Aerobic training; Auricular application pressure; Carotid atherosclerosis; Blood glucose; Blood lipid

The Differential Effect of Treadmill Exercise Intensity on Hippocampal Soluble Aβ and Lipid Metabolism in APP/PS1 Mice

Alzheimer's disease (AD) is characterized clinically by progressive impairments in learning and memory. Accumulating evidence suggests that regular exercise plays a neuroprotective role in aging-associated memory loss. Our previous study has confirmed that long-term treadmill exercise initiated either before or during the onset of β-amyloid (Aβ) pathology, was beneficial for reducing the levels of soluble Aβ and further improved cognition. In this study, in APP/PS1 mice, we assessed changes in soluble Aβ, and various blood biochemistry and molecular biological indices to assess whether exercise modulated lipid metabolism and thereby decelerated AD progression. Our results show that long-term treadmill exercise reduced the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, and increased the level of high-density lipoprotein cholesterol. Exercise also decreased the levels of soluble Aβ1-40 and Aβ1-42, down-regulated retinoid X receptor expression, and up-regulated liver X receptor, Apolipoprotein E, Low density lipoprotein receptor, Low density lipoprotein receptor-related protein 1, and ATP-binding cassette transporter A1 expression. This indicates that long-term treadmill exercise alters the lipoprotein content, increases lipid metabolism and cholesterol transportation, reduces the soluble Aβ, and therein plays an important neuroprotective role and delays AD progression. We further show that medium exercise intensity (60%–70% of maximal oxygen uptake) was more efficacious in increasing lipid metabolism and reducing blood lipid levels and soluble Aβ levels, than low-intensity exercise (45–55% of maximal oxygen uptake). This research has broad prospects and implications, and offers a theoretical basis for the prevention of AD.

Study of Dahuang-Huanglian-Xiexin decoction combined with conventional western medicine in patients with type 2 diabetes

Objective To evaluate the effects of the classical prescriptions Dahuang-Huanglian-Xiexin decoction combined with conventional western medicine on the lipid metabolism disorder and changes of intestinal microflora in patients with type 2 diabetes mellitus (T2DM). Methods A total of 120 patients who met the inclusion criteria were divided into the two group according to the treatment order, with 60 patients in each group. Both groups were given conventional hypoglycemic therapy, the control group was given bifidobacteria lactobacillus triple viable tablets, and the treatment group was given Dahuang-Huanglian-Xiexin decoction on the basis of the control group. Both groups were treated with 14 days for one course and 4 courses in total. The number of gram-positive coccus (G+c), gram-negative coccus (G-c), gram-positive bacillus (G+b) and gram-negative bacillus (G-b) in each 500 bacteria were observed under oil microscope, and the cocci/bacillus ratio were calculated. The TC and TG were detected by oxidase method, and HDL and LDL were detected by automatic biochemical analyzer. The FPG, 2 hPG and HbA1c were detected by automatic biochemical analyzer. TCM symptom scores were calculated. Results After treatment, the abdominal distension, congestion discomfort, and constipation score were significantly lower than the control group (t values were 3.685, 3.551 and 3.708, respectively, all Ps<0.05); Serum TG, TC and LDL-c levels were significantly lower than the control group (t values were 3.602, 3.581 and 3.421, respectively, all Ps<0.05); HDL-c level was significantly higher than that of the control group (t=3.358, P=0.046); Serum FPG, 2 hPG and HbA1c levels were significantly lower than the control group (t values were 3.502, 3.271 and 3.708, respectively, all Ps<0.05). After treatment, the G-c (271.47/500 ± 22.63/500 vs. 266.81/500 ± 22.36/500, t=3.792), G+b (81.26/500 ± 6.52/500 vs. 73.19/500 ± 6.94/500, t=3.511), G-b (183.76/500 ± 16.19/500 vs. 164.37/500 ± 15.83/500, t=3.306) levels in the treatment group significantly higher than those in the control group (P<0.05). After treatment, both c/b levels was (0.65 ± 0.13 vs. 0.87 ± 0.21, t=3.325) decreased significantly (P<0.05). Conclusions Dahuang-Huanglian-Xiexin decoction combined with conventional western medicine can improve the clinical symptoms of T2DM patients, reduce blood glucose and lipid levels, and inhibit the body mass and improve insulin resistance by adjusting the structure of intestinal flora, increasing probiotics and reducing pathogenic bacteria. Key words: Diabetes mellitus, type 2; Lipid metabolism disorders; Intestinal microflora; Dahuang-Huanglian-Xiexin decoction; Therapies, investigational

The Effect of Consumption Nata De Cocolawak on Lipid Serum Levels on Healthy Women

Temulawak (Curcuma xanthorrhiza Roxb.), traditionally known as a medicinal plant which is effective in reducing blood lipid levels. In this study we made a nata de coco product fortified with temulawak juice called nata de cocolawak. The purpose of this study was to determine the effect of supplementation of nata de cocolawak on total serum cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride-cholesterol, and serum pancreatic lipase levels. Respondents in this study were healthy adult women who were divided into 2 groups, there are group 1 consuming nata de coco products and group 2 consuming nata de cocolawak products. Each product was given as much as 100 grams consumed 3 times a day for 30 days. Nata de cocolawak products contain ascorbic acid, catechins, rutin, quercetin, alkaloids, and curcumin. Supplementation of nata de cocolawak products can significantly reduce serum total cholesterol, LDL-cholesterol, and serum pancreatic lipase levels (p 0.05) increase triglyceride-cholesterol levels. In this study, we can prove that regular consumption of nata de cocolawak products can affect blood lipid profile.

Akebia Saponin D inhibits the formation of atherosclerosis in ApoE−/− mice by attenuating oxidative stress-induced apoptosis in endothelial cells

Background and aimsAkebia Saponin D (ASD) is a major bioactive triterpenoid saponin compound isolated from the Chinese herb Dipsacus asper wall (DSW). DSW has been long used as an anti-Alzheimer disease and anti-osteoporosis agent in clinics. However, anti-atherosclerotic effects of ASD have not been fully investigated. The objective of this study is to further investigate the anti-atherosclerotic activities and mechanisms of ASD in vivo and in vitro. MethodsIn in vitro experiments, ASD (50, 100, and 200 μM) was used to explore the effects of preventing H2O2-induced endothelial cell apoptosis and the possible mechanism involved. In in vivo experiments, ApoE−/− mice were fed a high fat diet (HFD) and treated with atorvastatin (10 mg/kg/d), ASD (50, 150, 450 mg/kg/d), or the combination therapy (atorvastatin 10 mg/kg/d and ASD 150 mg/kg/d) for 14 weeks. ResultsWe found that ASD reduced the generation of reactive oxygen species, inhibited mitochondrial membrane potential (MMP) impairment, diminished the expression of Bax and Caspase-3, increased Bcl-2 expression, and inhibited apoptosis in endothelial cells. ASD significantly increased the expression of anti-oxidant enzymes (GSH, SOD, and CAT) in both liver and vascular tissue, reduced blood lipid levels (TG, TC, and LDL-C), and decreased lipid deposition in the liver and atherosclerotic lesion size in ApoE−/− mice. ConclusionsOur study revealed that ASD inhibited atherosclerosis development in ApoE−/− mice by inhibiting oxidative stress-induced endothelial cell apoptosis signaling pathway, and suggested that ASD might be a potential therapeutic drug in the prevention of atherosclerosis.

Hydrogen sulfide stabilizes atherosclerotic plaques in apolipoprotein E knockout mice

Hydrogen sulfide gas (H2S) has protective effects in the cardiovascular system that includes preventing the development of atherosclerosis when tested in several in vivo models. Plaque instability is a major risk factor for thromboembolism, myocardial infarction, and stroke, so we examined if H2S can promote plaque stability and the potential underlying mechanisms. Apolipoprotein E knockout mice fed an atherogenic diet were administered the exogenous H2S donor sodium hydrosulfide (NaHS) or pravastatin as a positive control daily for 14 weeks. NaHS significantly enhanced plaque stability by increasing fibrous cap thickness and collagen content compared to vehicle-treated controls. NaHS treatment also reduced blood lipid levels and plaque formation. Preservation of plaque stability by NaHS was associated with reductions in vascular smooth muscle cells (VSMCs) apoptosis and expression of the collagen-degrading enzyme matrix metallopeptidase-9 (MMP-9) in plaque. While pravastatin also increased fibrous cap thickness and reduced VSMC apoptosis, but did not enhance plaque collagen or reduce MMP-9 significantly, suggesting distinct mechanisms of plaque stabilization. in vitro, NaHS also decreased MMP-9 expression in macrophages stimulated with tumor necrosis factor-α by inhibiting ERK/JNK phosphorylation and activator protein 1 nuclear translocation. Moreover, H2S reduced caspase-3/9 activity, Bax/Bcl-2 ratio, and LOX-1 mRNA expression in VSMCs stimulated with oxidized low-density lipoprotein. These results suggest that H2S enhances plaque stability and protects against atherogenesis by increasing plaque collagen content and VSMC count. In conclusion, H2S exerts protective effects against atherogenesis at least partly by stabilizing atherosclerotic plaque.

Scutellarin exerts protective effects against atherosclerosis in rats by regulating the Hippo-FOXO3A and PI3K/AKT signaling pathways.

Atherosclerosis (AS), a progressive disorder, is one of the tough challenges in the clinic. Scutellarin, an extract from Herba Erigerontis, is found to have oxygen-free radicals scavenging effects and antioxidant effects. In this study, we aimed to investigate the anti-AS effects of scutellarin is related to controlling the Hippo-FOXO3A and PI3K/AKT signal pathway. To establish an AS model, the rats in the scutellarin and model groups were intraperitoneally injected with vitamin D 3 and then fed a high-fat diet for 12 weeks. In addition, in vitro angiotensin II-induced apoptosis of human aortic endothelial cells (HAECs) were used to establish models. Scutellarin significantly reduced blood lipid levels and increased antioxidase levels in both models. Additionally, scutellarin inhibited reactive oxygen species generation and apoptosis in HAECs. The impaired vascular barrier function was restored by using scutellarin in AS rats and in HAECs cells characterized by inhibiting mammalian sterile-20-like kinases 1 (Mst1) phosphorylation, Yes-associated protein (YAP) phosphorylation, forkhead box O3A (FOXO3A) phosphorylation at serine 207, nuclear translocation of FOXO3A, and upregulating protein expression of AKT and FOXO3A phosphorylation at serine 253. Scutellarin significantly reduced Bcl-2 interacting mediator of cell death (Bim), caspase-3, APO-1, CD95 (Fas), and Bax: Bcl-2-associated X (Bax) levels and activated Bcl-2: B-cell lymphoma-2 (Bcl-2). Scutellarin also significantly inhibited the expression of Mst1, YAP, FOXO3A at the messenger RNA level. When Mst1 was overexpressed or phosphoinositide 3-kinases suppressed, the effects of scutellarin were significantly blocked. In conclusion, the results of the present study suggest that scutellarin exerts protective effects against AS by inhibiting endothelial cell injury and apoptosis by regulating the Hippo-FOXO3A and PI3K/AKT signal pathways.

Mussel polysaccharide α-D-glucan (MP-A) protects against non-alcoholic fatty liver disease via maintaining the homeostasis of gut microbiota and regulating related gut-liver axis signaling pathways.

We isolated and characterized a Mussel polysaccharide, α-D-glucan (MP-A), from Mytilus coruscus earlier. In this work, the pharmacological activity and mechanisms of MP-A as an oral supplement for non-alcoholic fatty liver disease (NAFLD) were explored. High fat diet (HFD) was utilized to induce NAFLD in Sprague Dawley male rats and MP-A (0.6 g/kg) was supplemented for 4 weeks. The results showed that MP-A supplementation reduced blood lipid levels, intrahepatic lipid accumulation and NAFLD activity score in HFD-fed rats. Additionally, the analysis of 16S rDNA sequencing on gut microbiota samples revealed that HFD could induce microbial dysbiosis. However, MP-A supplementation could remodel gut microbiota structure, inhibit LPS-TLR4-NF-κB pathway activation, and restrain subsequent inflammation factors secretion. Furthermore, MP-A regulated the lipid metabolism by promoting the production of short chain fatty acids and suppressing PPAR γ and SREBP-1c expression. Our results support that MP-A can prevent against NAFLD and act as an oral supplementation for hepatoprotection via modulating gut microbiota and related gut-liver axis signaling pathways.

Therapeutic Effect of Chitooligosaccharide Tablets on Lipids in High-Fat Diets Induced Hyperlipidemic Rats.

Chitooligosaccharide is beneficial for inhibiting dyslipidemia and reducing atherosclerotic and hyperlipidemic risk. The purpose of this study was to investigate the cholesterol-regulating effects and potential mechanisms of Chitooligosaccharide tablets (CFTs) in high-fat diet-induced hyperlipidemic rats. The results revealed that CFTs can regulate serum lipid levels in hyperlipidemic rats in a dosage-dependent manner. Synchronously, gene expressions related to cholesterol excretion were upregulated in a dosage-dependent manner, including cholesterol 7α-hydroxylase (CYP7A1), liver X receptor α (LXRA), peroxisome proliferation-activated receptor-α (PPARα) and low-density lipoprotein receptor (LDLR), whereas cholesterol synthetic gene expressions including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and sterol-responsive element binding protein-2 (SREBP2) were reduced. This work highlights that CFTs have potential as natural products to prevent and treat metabolic hyperlipidemia syndrome, probably due to the reduction of cholesterol biosynthesis and through cholesterol elimination; they also improve the pathological changes of liver tissue in rats, alleviate liver damage, maintain normal lipid metabolism in the liver, ameliorate hepatic glycolipid disorders and accelerate TC operation, and reduce blood lipid levels.

Pengaruh Pemberian Ekstrak Etanol Daun Ubi Jalar Ungu (Ipomoea Batatas (L.) Lam) terhadap Kadar Kolesterol Ldl Tikus Hiperkolesterolemia

Hypercholesterolemia is still a health problem today because it is associated with the onset of cardiovascular disorders with various complications. High cholesterol levels carried by the blood will accumulate in the arteries that cause atherosclerosis. Blood clots and blockage of blood vessels can result in the stroke or heart attack. Flavonoids that are found in purple sweet potato leaves are quercetin. Quercetin has antioxidant effects that can improve blood vessel endothelial function, reduce LDL sensitivity to free radical effects, and reduce blood lipid levels. This study aims to determine the effect of ethanol extract of purple sweet potato leaves on LDL cholesterol level of hypercholesterolemia rat. The experiment was conducted experimentally using 2 groups of Wistar rats (each group consisting of 5 tails), namely the control group and the treatment group. Induction of hypercholesterolemia was performed with a high-fat diet for 7 days. The purple sweet potato ethanol extract was administered sonde in the treatment group with a quercetin dose of 2 mg /kg/day for 14 days and the measurement of LDL cholesterol was performed on days 10 and 24 by the CHOD-PAP method. Data were analyzed by Paired t-test. The results showed that LDL cholesterol level in the treatment group showed that 5 mice had decreased, the mean decrease of 32,49 mg/dl while control group 3 decreasing, mean 0,65 mg /dl. There was a significant difference (p &lt;0.05) on changes in LDL cholesterol levels in the treatment group. Provision of purple sweet potato ethanol extract with quercetin dose of 2 mg/kg for 14 days can decrease LDL cholesterol level of hypercholesterolemia rat. From the results of this study is expected to optimize the utilization of purple sweet potato leaves (Ipomoea batatas (L.) Lam) as a drug for lowering LDL cholesterol.

Effects of Xuezhikang (Red Yeast Rice) on Blood lipids, Hemorheology and the Expression of P65 and Tissue Factor in Atherosclerotic Rats

Objective: To observe the effects of Xuezhikang (red yeast rice) on blood lipids, blood rheology, and expression of P65 and tissue factor, and to explore the anti-atherosclerosis effect and related mechanisms of Xuezhikang (red yeast rice). Methods: 32 Wistar rats were randomly divided into normal control group, Xuezhikang treatment group, lovastatin treatment group and atherosclerosis model group (8 in each group). blood lipids, blood rheology, malondialdehyde (MDA), total antioxidant capacity (t-AOc), and expression of aortic tissue factor (tF) and P65 were measured in each group. results: (1) Both Xuezhikang and lovastatin could reduce blood lipid levels, but there was no significant difference between the two groups; (2) Both Xuezhikang and lovastatin can improve the hemorheology of atherosclerotic rats, but the difference between the two groups is not signifcant; (3) Compared with lovastatin, Xuezhikang inhibited the expression of TF and P65 in aorta of rats with atherosclerosis; (4) Compared with lovastatin, the Xuezhikang group had lower MDA levels and higher T-AOC. Conclusion: Xuezhikang can improve blood lipid levels and hemorheology in rats with atherosclerosis. Compared with lovastatin, Xuezhikang has stronger effects on inhibiting oxidative stress and down-regulating the expression of tissue factor and P65.

Standardized Xin-Ke-Shu tablets improves the disturbances of lipid, energy, and amino acid metabolism in a rabbit model of atherosclerosis

Objective: Xin-Ke-Shu (XKS), a patent drug, used to treat coronary artery diseases in China for many years. Previous research indicates that XKS has similar therapeutic effect as atorvastatin (AS) against atherosclerotic in rabbits. However, biochemical assays demonstrate that XKS could have a different therapeutic mechanism from AS. The aim of this study is to explore the mechanism of XKS therapeutic effect, especially those different from AS. Materials and Methods:1H nuclear magnetic resonance-based metabonomics were applied to profile the low-molecular-weight polar metabolites in the plasma of rabbits fed a high cholesterol diet. Results: Seven of the eleven pathological biomarkers related to atherosclerosis in rabbits were mediated by XKS treatment, namely low-density lipoprotein/very-low-density lipoprotein (LDL/VLDL), lactate, citrate, phosphatidylcholine, glutamine, creatinine, and methionine, as well as two characteristic metabolites of pyruvate and α-glucose. These metabolites involved lipid, energy, and amino acid metabolism, and all could be considered XKS treatment targets. However, AS only affected the metabolic disorders associated with LDL/VLDL and phosphatidylcholine, which is mainly target lipid metabolism. Conclusions: This study indicates that the anti-atherosclerosis effects of AS mainly involve reducing blood–lipid levels, but those of XKS involve a multitargeted activity.

Effects of sanshoamides and capsaicinoids on plasma and liver lipid metabolism in hyperlipidemic rats.

The objective of this study was to determine the effects of sanshoamides and capsaiciniods on plasma and liver lipid levels and the mRNA expression levels of key receptors involved in cholesterol metabolism in hyperlipidemic rats. A total of 56 three-week-old female Sprague-Dawley rats were assigned to 7 treatment groups based on initial body weight (n = 8 rats per group). With certain combinations of sanshoamides and capsaicinoids significantly increased food intake, reduced lipid levels in blood and liver, improved histological characteristics of a fatty liver, down regulated mRNA expression levels of cholesterol 7-alpha-hydroxylase (CYP7A1), 3-hydroxyl-3-methylglutary CoA (HMG-CoA) and Farnesoid X Receptor (FXR) in liver and apical sodium-dependent bile acid transporter, Ileal Bile Acid Binding Protein and FXR in the ileum in hyperlipidemic rats. These results indicated that dietary supplementation with sanshoamides and capsaicinoids reduced blood lipid levels and improved cholesterol metabolism in hyperlipidemic rats.

Gold nanoparticles as cell regulators: beneficial effects of gold nanoparticles on the metabolic profile of mice with pre-existing obesity

BackgroundWe have previously shown that intraperitoneal injection of gold nanoparticles (AuNPs, 20–30 nm) into mice, decreases high-fat diet (HFD) induced weight gain and glucose intolerance, via suppression of inflammatory responses in both fat and liver tissues. This study investigates whether AuNPs provide similar benefit to mice with pre-existing obesity. Male C57BL/6 mice were fed a HFD for 15 weeks. AuNPs (OB-EAu 0.0785 μg/g/day, OB-LAu 0.785 μg/g/day, OB-HAu7.85 μg/g/day, ip) were administered to subgroups of HFD-fed mice over the last 5 weeks. Control group was fed standard chow and administered vehicle injection.ResultsOnly the OB-LAu group demonstrated significant weight loss (12%), while all AuNP treated groups showed improved glycaemic control and reduced blood lipid levels. In the fat tissue, mRNA expression of pro-inflammatory markers were unchanged following AuNP treatment, while glucose and lipid metabolic markers were improved in OB-LAu and OB-HAu mice. In the liver, AuNP treatment downregulated inflammatory markers and improved lipid metabolic markers, with marked effects in OB-EAu and OB-LAu groups.ConclusionsAuNP treatment can improve glucose and fat metabolism in mice with long-term obesity, however weight loss was only observed in a single specific dose regime. AuNP therapy is a promising new technology for managing metabolic disorders in the obese.

Chitosan-functionalized lipid-polymer hybrid nanoparticles for oral delivery of silymarin and enhanced lipid-lowering effect in NAFLD

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic disease that causes excessive hepatic lipid accumulation. Reducing hepatic lipid deposition is a key issue in treatment and inhibition of NAFLD evolution. Silymarin is a potent hepatoprotective agent; however, it has low oral bioavailability due to its poor aqueous solubility and low membrane permeability. Unfortunately, few studies have addressed the development of convenient oral nanocarriers that can efficiently deliver silymarin to the liver and enhance its lipid-lowering effect. We designed silymarin-loaded lipid polymer hybrid nanoparticles containing chitosan (CS-LPNs) to improve silymarin bioavailability and evaluated their lipid-lowering effect in adiponutrin/patatin-like phospholipase-3 I148M transgenic mice, an NAFLD model.ResultsCompared to chitosan-free nanoparticles, CS-LPNs showed 1.92-fold higher uptake by fatty liver cells. Additionally, CS-LPNs significantly reduced TG levels in fatty liver cells in an in vitro lipid deposition assay, suggesting their potential lipid-lowering effects. The oral bioavailability of silymarin from CS-LPNs was 14.38-fold higher than that from suspensions in rats. Moreover, compared with chitosan-free nanoparticles, CS-LPNs effectively reduced blood lipid levels (TG), improved liver function (AST and ALT), and reduced lipid accumulation in the livers of mice in vivo. Reduced macrovesicular steatosis in pathological tissue after CS-LPN treatment indicated their protective effect against liver steatosis in NAFLD.ConclusionsCS-LPNs enhanced oral delivery of silymarin and exhibited a desirable lipid-lowering effect in a mouse model. These findings suggest that CS-LPNs may be a promising oral nanocarrier for NAFLD therapeutics.

Pathogenesis of Abnormal Hepatic Lipid Metabolism Induced by Chronic Intermittent Hypoxia in Rats and the Therapeutic Effect of N-Acetylcysteine.

BackgroundThe pathogenesis of chronic intermittent hypoxia (CIH)-induced abnormal hepatic lipid metabolism in rats remains unclear. Here, we investigated the therapeutic effect of N-acetylcysteine (NAC) on abnormal hepatic lipid metabolism.Material/MethodsRats were subjected to hypoxia and NAC treatment, and evaluated in terms of hepatic lipid metabolism, hepatocyte ultrastructure, oxidative stress in hepatocytes, expression of nuclear factor-kappa B (NF-κB) and inflammatory cytokines (IL-1β, IL-6, and TNFα), serum lipoprotein lipase (LPL) levels, and blood lipids (triglycerides and cholesterol).ResultsCompared to the normoxic control group, animals in the hypoxic model group showed significant body weight gain; abnormal hepatic lipid metabolism; lipid vacuolization; accumulation of lipid droplets; abundant autophagosomes and lysosomes; significant increases in oxidative stress, inflammation level, and blood lipid levels; and significantly reduced LPL levels. Compared to control animals, rats in the treatment group exhibited normal body weight gain, improved lipid metabolism, fewer lipid droplets, alleviated ultrastructural injuries, decreased oxidative stress and inflammation level, as well as elevated LPL and reduced blood lipid levels.ConclusionsThe harmful effects of CIH on rat liver are possibly associated with the reactive oxygen species (ROS)/NF-κB signaling pathway. NAC is capable of attenuating lipid metabolism alterations and abnormal body weight gain in the CIH rat model, via a possible mechanism related to inhibition of ROS/NF-κB signaling.

Scutellarin ameliorates nonalcoholic fatty liver disease through the PPARγ/PGC-1α-Nrf2 pathway

Nonalcoholic fatty liver disease (NAFLD) is characterised by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Scutellarin is a flavonoid glycoside having antioxidative stress activity. Our current study aims to investigate the molecular mechanism of scutellarin ameliorating NAFLD. Scutellarin treatment was applied to male C57BL/6 mice maintained on a high-fat diet (HFD) and HepG2 cells challenged with oleic acid. The antioxidation biochemical indicators and lipid levels in the liver and cells were detected by kits. Liver pathology was observed by light microscope, Oil Red O staining, and transmission electron microscope (TEM). In addition, quantitative real-time polymerase chain reactions (qRT-PCR) and western blot assays were employed to detect the mRNA and protein levels of various antioxidative-related genes in the presence or absence of peroxisome proliferator-activated receptor gamma (PPARγ); inhibitor GW9662. Our results showed that scutellarin could significantly reduce blood lipid levels and enhance antioxidative capacities in both the models. In addition, scutellarin treatment conspicuously activated PPARγ, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear factor erythroid-2-related factor (Nrf2), haem oxygenase-1 (HO-1), glutathione S-transferase (GST), and NAD(P)H quinone dehydrogenase one (NQO1), while it significantly inhibited nuclear factor kappa B (NF-κB), Kelch-like ECH-associated protein 1 (Keap1) at both the mRNA and protein levels. However, after interfered by GW9662, scutellarin effect was significantly decreased. The experimental data demonstrated that scutellarin showed strong hypolipidaemic, antioxidative, and liver protective activity which could be attributed to its regulating activity in the PPARγ/PGC-1α-Nrf2 signaling pathway.

Dislipidemia: definition, diagnostics and treatment

The review article presents the pathogenetic role of atherosclerotic vascular lesions in the development of cardiovascular diseases. The relationship between atherosclerosis and inflammation, which is characterized by the identical mechanism in the early phases, which includes the enhancement of the interaction between the vascular endothelium and circulating leukocytes is shown. The definition of such concepts as dyslipidemia, hyperlipoproteinemia and hyperlipidemia is given. The classification of hyperlipoproteinemia by Fredrickson, the clinical classification of dyslipidemia, proposed by the Ukrainian Scientific Society of Cardiologists, 2011 is considered. The correction of dyslipidemia, by both non-medicamentous measures, and drug treatment according to different variants of dyslipidemia is shown. The main groups of lipid-lowering drugs are listed. Their main mechanisms of action to reduce blood lipid levels are noted, and their side effects are listed. General recommendations are given on the monitoring of lipids and liver enzymes in patients taking lipid-lowering therapy.

Preventive effect of L-carnitine on the disorder of lipid metabolism and circadian clock of mice subjected to chronic jet-lag.

Circadian clock plays an essential role in orchestrating daily physiology, and its disruption can evoke metabolic diseases such as obesity. L-Carnitine can reduce blood lipid levels, and ameliorate fatty liver through regulating lipid metabolism. However, whether L-Carnitine administration may affect the disturbance of lipid metabolism and circadian rhythm of mice induced by prolonged circadian disruption is still unknown. Herein, we investigated the effects of L-Carnitine on conditions of circadian clock and lipid metabolism through a chronic jet-lag mice model which was developed by reversing 12 h light/12 h dark cycle every 4 days for a continuous 12 weeks. Results showed that L-Carnitine administration significantly decreased levels of serum glutamic-oxaloacetic transaminase (GOT) and triglycerides (TG), which were remarkably elevated by chronic jet-lag. More importantly, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that L-Carnitine supplementation would effectively counteract the negative alterations in gene expression which related to lipid metabolism (Srebp1, Acaca, Fasn, and Scd1), metabolic regulator (mTOR) and circadian rhythm (Bmal1, Per1, Cry1 and Dec1) in the liver of mice subjected to the chronic jet-lag. As a conclusion, L-Carnitine was partly effective in preventing the disruption of circadian clock and lipid metabolic disorders induced by the chronic jet-lag.