High-fat Diet-induced Hyperlipidemia Research Articles

Inhibition of pancreatic lipase, α-glucosidase, α-amylase, and hypolipidemic effects of the total flavonoids from Nelumbo nucifera leaves

Ethnopharmacological relevanceNelumbo nucifera Gaertn. leaves have been used as medicinal herbs in the past 1300 years, specifically utilized to cure hyperlipidemia, hyperglycemia, and obesity. It has been recorded in the most famous medicinal book in China for more than 400 years. The present study aims to identify the potential therapeutic activities of the flavonoids isolated from Nelumbo nucifera leaves. Materials and methodsNelumbo nucifera leaf flavonoids (NLF) were tested for the inhibition of lipase, α-glucosidase, and α-amylase activities in vitro. A single dose of NLF was administered by oral gavage in mice for acute toxicity. Wistar rats with high-fat diet-induced hyperlipidemia and two other animal models were used to evaluate the hypolipidemic effects of NLF. ResultsOur in vitro biochemistry tests revealed that the NLF showed high inhibitory activity against porcine pancreatic lipase, α-amylase, and α-glucosidase with IC50 values of 0.38±0.022, 2.20±0.18, and 1.86±0.018mg/mL, respectively. Furthermore, the NLF significantly lowered the lipid components, such as the total cholesterol, triglycerides, low-density lipoprotein cholesterol, and malondialdehyde, in various established in vivo systems and raised the high-density lipoprotein cholesterol. Moreover, the NLF alleviated high-fat diet-induced lipid accumulation in the liver. ConclusionsThe results demonstrate that NLFs can effectively ameliorate hyperlipidemia and inhibit the key enzymes related to type 2 diabetes mellitus. Our findings may provide new pharmacological basis for the treatment of hyperlipidemia, hyperglycemia, and obesity using NLFs.

Modulatory effects of functional rice cultivars giant embryo and Aranghyangchal on the body weight and lipid metabolism in mice fed with a high fat diet

The effects of the functional rice cultivars giant embryo and Aranghyangchal on the body weight and lipid metabolism in male C57BL/6N mice under high fat diet conditions were investigated. The animals were randomly placed into four dietary groups: normal control (NC group), high fat (HF group), and high fat supplemented with giant embryo (HF-GE group) or Aranghyangchal (HF-AR group). After 8weeks, a marked increase in the body weight and plasma triglyceride and total cholesterol concentrations were found in the HF mice relative to the control group. However, the addition of the functional rice samples in the high fat diet reduced the body weight gain and significantly decreased the lipid levels through inhibition of lipogenesis and regulation of adipokine production. The results demonstrate that the functional rice grains giant embryo and Aranghyangchal may both be useful as biomaterials in the development of functional food with therapeutic potential against high fat diet-induced hyperlipidemia.

A Mechanism-based Pharmacological Evaluation of Efficacy of Trigonella foenum graecum (Fenugreek) Seeds in Regulation of Dyslipidemia and Oxidative Stress in Hyperlipidemic Rats

: Alcoholic extract of Trigonella foenum graecum seeds [fenugreek seed extract (FSE)] was studied in triton-induced and high-fat diet-induced hyperlipidemia to evaluate antidyslipidemic effect. Plasma cholesterol (26.19%) and triglycerides (36.6%) were found to be lowered by FSE maximum at a dose of 200 mg/kg body weight in triton-treated hyperlipidemic rats. Chronic feeding of FSE (200 mg/kg body weight) caused lowering in plasma and hepatic lipid levels by activating lecithin-cholesterol acyltransferase (47%), postheparin lipolytic activity (35%), triglyceride lipase (34%), lipoprotein lipase (20.8%), and increased excretion of fecal bile acids (36%-45%). The FSE shows potent antioxidant activity in both in vitro and in vivo systems. It inhibited generation of superoxide anion and hydroxyl free radicals in both enzymatic and nonenzymatic systems significantly at 200 µM concentration. Furthermore, FSE normalizes the activities of antioxidant enzymes, that is, superoxide dismutase and catalase, and reduces plasma lipid peroxidation (33.9%), hepatic 4-hydroxynonenal (27%), and isoprostanes (28%). Data of the present study demonstrated that the T. foenum graecum seed extract has both antidyslipidemic and antioxidant properties.

Dill seed extract improves abnormalities in lipid metabolism through peroxisome proliferator‐activated receptor‐α (PPAR‐α) activation in diabetic obese mice

Dill, a small annual herb, is widely used as a flavoring agent in dishes including salads. It has been demonstrated that dill extract and its essential oil show hypolipidemic effects in rats. However, the mechanism of these effects has not been elucidated yet. We found that dill seed extract (DSE) activated peroxisome proliferator-activated receptor-α (PPAR-α), an indispensable regulator for hepatic lipid metabolism, by luciferase assay. Thus, we performed DSE feeding experiments using diabetic obese model KK-Ay mice to examine the effects of DSE on PPAR-α activation in vivo. A 4-week feeding of DSE contained in a high-fat diet decreased plasma triacylglyceride and glucose levels and increased the mRNA expression levels of fatty acid oxidation-related genes in the liver. In addition, the DSE feeding as well as bezafibrate (a PPAR-α potent agonist) feeding increased oxygen consumption rate and rectal temperature. These results indicate that DSE suppresses high-fat diet-induced hyperlipidemia through hepatic PPAR-α activation.

Sesamol Treatment Reduces Plasma Cholesterol and Triacylglycerol Levels in Mouse Models of Acute and Chronic Hyperlipidemia

The active constituents of Sesamum indicum, sesamin and sesamolin, have already been explored for hypolipidemic action. In this study we have explored the anti-dyslipidemic activity of another active component and metabolite of sesamolin (sesamol), by using acute models of hyperlipidemia viz., a fat tolerance test, a tyloxapol-induced hyperlipidemia model and a chronic model of hyperlipidemia viz., a high-fat diet-induced hyperlipidemia model in Swiss albino mice. Sesamol (100 and 200mg/kg) significantly (P<0.05) decreased triacylglycerol absorption in the fat tolerance test by showing a dose-dependent decrease in triacylglycerol levels. The hypolipidemic effect of sesamol at 200mg/kg was equivalent to 10mg/kg of orlistat. In the tyloxapol-induced hyperlipidemia model, Sesamol at 200mg/kg reversed the elevated levels of cholesterol and triacylglycerol compared with the tyloxapol group at 12 and 24h, which indicates its probable effect on cholesterol synthesis. Chronic hyperlipidemia in mice was produced by feeding a high-diet, a mixture of cholesterol (2% w/w), cholic acid (1% w/w) and coconut oil 30% (v/w) with standard powdered standard animal chow (up to 100g). Niacin (100mg/kg) and sesamol (100mg/kg) significantly (P<0.05) reduced the elevated body weight compared with the high fat diet control group. Elevated levels of cholesterol and triacylglycerol were significantly (P<0.05) reversed by the sesamol (50 and 100mg/kg), implying that it might reduce the absorption and increase the excretion of cholesterol as well.

Evaluation of Hypolipidemic Effects of Lyciumbarbarum (goji Berry) in a Murine Model

Lycium barbarum L. Solanaceae a traditi onal medicinal plant of China has been accorded a very high safety value. It has been known to possess various benefi cial eff ects like reducti on of blood glucose and serum lipids in alloxan-induced diabetes models, anti -ageing, immuno-modulati ng, anti -cancer, anti -fati gue, and male ferti lity-facilitatory acti ons. The present study is an att empt to explore the hypolipidemic eff ects of powdered L. barbarum in high fat diet-induced model of hyperlipidemia. Powdered L. barbarum fruit extract (250mg/kg and 500mg/kg) was administered to Wistar albino rats fed on a cholesterol-rich high-fat diet for 45 days. The eff ects were compared with the standard drug atorvastati n (10 mg/kg/day, oral). Aft er 30 days of treatment, the lipid profi le of the blood samples of the experimental rodents was evaluated.The data presented as mean±SEM were analysed using one-way ANOVA followed by Tukey’s post hoc test. P<0.05 was considered as stati sti cally signifi cant. In the present study, L. barbarum powdered extract showed a signifi cant reducti on in the total cholesterol, triglycerides and very low density lipoprotein-cholesterol levels at both the doses employed (p<0.05). However, reducti on in low density lipoprotein-cholesterol levels was signifi cant (p<0.05) only at the dose of 500 mg/kg when compared to the standard drug group. The increase in high-density lipoprotein levels was signifi cant only at 250 mg/kg. The data thus suggests the positi ve anti -hyperlipidemic acti vity of L. barbarum in high fat diet-induced hyperlipidemia in rats.

Natural Products for the Treatment of Obesity, Metabolic Syndrome, and Type 2 Diabetes

Globally, the incidence of obesity, metabolic syndrome, and diabetes (OMD) are continuously on the rise because of rapid changes in human life-style and dietary habits. Herbal extracts are of special interest in treating combination of these diseases because of their multipronged mode of action. The list of potential herbals to control metabolic diseases is ever-expanding. However, because of poor characterization and safety issues, these herbs face limitations for their clinical usage. This special issue is a collection of research and review articles on preclinical and clinical benefits of herbals in controlling OMD. This special issue contains 24 articles accepted from a total of 37 submissions consisting of 20 research articles, 3 review articles, and 1 clinical study. The research articles in this issue can be broadly divided into three disease categories—nonalcoholic steatohepatitis (NASH), obesity, and diabetic complications. Four articles of this special issue focus on evaluating the protective role of herbal extracts on NASH. The studies by X. R. Yang et al. “Effect of dietary cocoa tea (Camellia ptilophylla) supplementation on high-fat diet-induced obesity, hepatic Steatosis, and hyperlipidemia in mice” and H.-Y. Jung et al. “The Korean mistletoe (Viscum album coloratum) extract has an antiobesity effect and protects against hepatic steatosis in mice with high-fat diet-induced obesity” report the potential benefits of Camellia ptilophylla and Viscum album coloratum extracts against HFD-induced NASH. Another two articles evaluated protective effects of biherbal combination (S. miltiorrhiza, G. jasminoides and Grape Pomace, Omija Fruit) in ameliorating experimental NASH. This special issue also contains five articles that focus on antiobesity potential of herbal extracts. These detailed studies evaluated the benefits of 10 herbs and their potential mechanisms responsible in controlling obesity using experimental HFD-fed mice/rat in vivo and 3T3L1 preadipocyte in vitro models. Modulation of PPARγ was a key antiobesity mechanism of Artemisia iwayomogi, Codonopsis lanceolata, Populus balsamifera and its active component (salicortin), and beta-glucan-rich extract from Pleurotus sajor-caju (Fr.) Singer. H.-Y. Shin et al. reported an activation of AMP-activated protein kinase by extract of six herbal medicines (OB-1). In this special issue, 11 articles focus on the potential benefits of various herbal extracts/phytocompounds on diabetes-induced insulin resistance, nephropathy, retinopathy, cardiomyopathy, and inflammation. A. l. Al-Malki showed oat extract to be beneficial for diabetic nephropathy and retinopathy by modulating nuclear factor kappa B (NF-kB). Inhibition of aldose reductase activity by scopoletin ameliorated cataractogenesis in galactose-fed rats (J. Kim et al.). Boehmeria nivea extract (S. H. Kim et al.) and swertiamarin (T. P. Patel et al.) regulated experimental insulin resistance by modulating PPARγ. In another report, S. Kadan et al. evaluated effect of eight antidiabetic medicinal plants extracts on GLUT 4 translocation. The benefits of fisetin and an ayurvedic herbal formulation (Kal-1) on diabetes-induced inflammation was also reported. Further, quercetin was shown to preserve β-cell mass and function in fructose-fed hyperinsulinemic rats via modulating pancreatic akt/foxo1 activation. Berberine ameliorated glucose- and insulin-induced cardiomyocyte hypertrophy by modulating PPARα/NO. In an interesting article by S. E. Martinez et al. pharmacometrics of an antidiabetic compound, 3-methoxypterostilbene was reported. 3-Methoxypterostilbene inhibited α-glucosidase and α-amylase activity and exhibited approximately 50% bioavailability. Three review articles were also incorporated in this special issue. A review by Y. Liu et al. (recent updates on beneficial role of berberine in controlling NASH) provides detailed account on molecular regulation of lipid metabolism and NASH by berberine. In another review by C. D. Lorenzo et al. the use of in vitro and clinical approaches to assess the benefits of plant food supplements is critically discussed. The potential benefits of Kampo, a Japanese traditional medicine, in treating obesity was reviewed by J.-i Yamakawa et al. based on basic and clinical evidence. The only clinical study as a part of this special issue focuses on evaluating body weight lowering effects of herbal extract-THI (target herbal ingredient) on exercising healthy overweight humans following a two-month randomized double-blind, placebo-controlled trial. The study reports a significant reduction in body weight indicating its potential antiobesity effect. We envisage that this special issue will attract broad interest in the fields of obesity, metabolic syndrome, and type 2 diabetes and encourage the perusal of in-depth molecular and cellular mechanistic investigations into the use of natural products, in particular the herbal therapies for metabolic disorders and their complications.

Effect of Dietary Cocoa Tea (Camellia ptilophylla) Supplementation on High-Fat Diet-Induced Obesity, Hepatic Steatosis, and Hyperlipidemia in Mice

Recent studies suggested that green tea has the potential to protect against diet-induced obesity. The presence of caffeine within green tea has caused limitations. Cocoa tea (Camellia ptilophylla) is a naturally decaffeinated tea plant. To determine whether cocoa tea supplementation results in an improvement in high-fat diet-induced obesity, hyperlipidemia and hepatic steatosis, and whether such effects would be comparable to those of green tea extract, we studied six groups (n = 10) of C57BL/6 mice that were fed with (1) normal chow (N); (2) high-fat diet (21% butterfat + 0.15% cholesterol, wt/wt) (HF); (3) a high-fat diet supplemented with 2% green tea extract (HFLG); (4) a high-fat diet supplemented with 4% green tea extract (HFHG); (5) a high-fat diet supplemented with 2% cocoa tea extract (HFLC); and (6) a high-fat diet supplemented with 4% cocoa tea extract (HFHC). From the results, 2% and 4% dietary cocoa tea supplementation caused a dose-dependent decrease in (a) body weight, (b) fat pad mass, (c) liver weight, (d) total liver lipid, (e) liver triglyceride and cholesterol, and (f) plasma lipids (triglyceride and cholesterol). These data indicate that dietary cocoa tea, being naturally decaffeinated, has a beneficial effect on high-fat diet-induced obesity, hepatomegaly, hepatic steatosis, and elevated plasma lipid levels in mice, which are comparable to green tea. The present findings have provided the proof of concept that dietary cocoa tea might be of therapeutic value and could therefore provide a safer and cost effective option for patients with diet-induced metabolic syndrome.

Hypolipidemic and antioxidative effects of rice bran and phytic acid in high fat-fed mice

The influence of rice bran and phytic acid on lipid metabolism and antioxidative status in high fat-fed mice was investigated. The mice were given high fat diet (HF) or high fat diet supplemented with rice bran (HF-RB) or phytic acid (HF-PA) for 7 weeks. The control mice (NC) received normal diet. The HF mice showed marked increase in body weight, total cholesterol levels, hepatic triglyceride concentration, and lipid peroxidation rate compared with NC group. Also, a significant decrease in antioxidant enzyme activities was observed in HF animals. Addition of rice bran and phytic acid in the diet counteracted this high fatinduced hyperlipidemia and oxidative stress, mainly by increasing fecal lipid excretion and regulation of antioxidant and lipogenic enzyme activities. These findings illustrate that rice bran and phytic acid possess antihyperlipidemic action and antioxidant status-improving ability, and may be beneficial as dietary supplements in the management of high fat diet-induced hyperlipidemia.

CytochromeP-450 CYP2E1 knockout mice are protected against high-fat diet-induced obesity and insulin resistance

Conventional (whole body) CYP2E1 knockout mice displayed protection against high-fat diet-induced weight gain, obesity, and hyperlipidemia with increased energy expenditure despite normal food intake and spontaneous locomotor activity. In addition, the CYP2E1 knockout mice displayed a marked improvement in glucose tolerance on both normal chow and high-fat diets. Euglycemic-hyperinsulinemic clamps demonstrated a marked protection against high-fat diet-induced insulin resistance in CYP2E1 knockout mice, with enhanced adipose tissue glucose uptake and insulin suppression of hepatic glucose output. In parallel, adipose tissue was protected against high-fat diet-induced proinflammatory cytokine production. Taken together, these data demonstrate that the CYP2E1 deletion protects mice against high-fat diet-induced insulin resistance with improved glucose homeostasis in vivo.

Trans-(3R,5S)-Atorvastatin Ca의 합성 및 Rat에서 고지방식이로 유도된 고지혈증 치료효과

Abstract cis -(3R,5R)-Atorvastatin Ca (1) used for hyperlipidemia have four stereomers. However, It is very difficult to prepare stereoselective stereomers. In this paper, the reduction of 3,5-diketo atorvastatin ester (3) was performed using Me 4 NHB(OAc) 3 in acetic acid as a reductant and showed excellent stereoselectivity in the double reduction of 3,5-diketo atorvastatin ester (3). As a result, reduction of compound 3 by Me 4 NHB(OAc) 3 was purely obtained with cis -(3R,5R)-atorvastatin ester (4) of 1.5% and trans -(3R,5S)-atorvastatin ester (5) of 98.5%. Also, cis-(3R,5R)-atorvastatin Ca (1) and trans-(3R,5S)-atorvastatin Ca (7) were used to determine efficacy in the treatment of liver damage and hyperlipidemia induced by a high-fat diet in rats and to study the performance of the January 2010 experient was conducted. As a result, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c), and triglyceride (TG) levels of compound 1 and 7 groups were 93.0±0.5, 43.5±0.8, 40.4±1.4, 45.6±0.9 mg/㎗ and 110.0±0.7, 33.3±0.6, 65.8±1.9, 54.8±1.2 mg/㎗, respectively. Atherogenic index (AI) and cardiac risk factor (CRF) in compound 1 and 7 were 1.14±0.05, 2.14±0.05 and 2.31±0.06, 3.31±0.06, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 51.9±4.6, 16.0±2.1 IU/l and 75.8±4.4, 35.1±9.7 IU/l. Taken together, while compound 1 treat against high-fat diet-induced hyperlipidemia by attenuating hepatic lipid depots and reducing oxidative stress, compound 7 group had a low curative effect on hyperlipidemia induced by a high-fat diet in rats. These findings suggest that new method about synthesis of stereoselective stereomers and indicate that it may consider using in a clinical trial.

Microwave‐Assisted Synthesis, Hypolipidemic and Hypoglycemic Activity of Some Novel 2‐(4‐(2‐Amino‐6‐(4‐substituted phenyl)‐pyrimidin‐4‐yl)‐phenoxy)‐2‐methyl Propanoic Acid Derivatives

A novel series of aminopyrimidines containing the phenoxy isobutyric acid group as a pharmacophore was synthesized using conventional and microwave assisted methods of synthesis. The compounds were synthesized in good yields (70-89%) by the microwave-assisted one-pot protocol in much shorter reaction times. The synthesized compounds were evaluated for their hypolipidemic and hypoglycemic activity by high-fat diet-induced hyperlipidemia and hyperglycemia in male Sprague-Dawley rats. The present investigation showed significant antihyperlipidemic and antihyperglycemic activity for all compounds of the series when compared with the standard drug. Structure-activity relationship (SAR) for the series were developed by comparing total lipid profile data of synthesized compounds with fenofibrate as standard drug.

Comparative evaluation of the hypolipidemic effects of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) in high fat-fed mice

The effect of hydroxyethyl methylcellulose (HEMC), in comparison with hydroxypropyl methylcellulose (HPMC), on the body weight and lipid metabolism in mice fed with high fat diet was investigated. The animals were given normal control diet (NC group), high fat diet (HF group), or high fat diet supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group) for 6weeks. At the end of the experimental period, both HF+HEMC and HF+HPMC groups showed reduced body weight, body fat, plasma triglyceride and total cholesterol contents, atherogenic index and free fatty acid level, and increased HDL-cholesterol concentration relative to the HF group. The hypolipidemic effect was partly due to the inhibition of lipogenesis and regulation of adipokine production. These findings demonstrate that compared with HPMC, HEMC was similarly effective in improving the lipid metabolism under high fat diet condition and may be useful in the prevention and treatment of high fat diet-induced hyperlipidemia.

Hypolipidemic and anti-inflammatory properties of Abacopterin A from Abacopteris penangiana in high-fat diet-induced hyperlipidemia mice

This study was to investigate the hypolipidemic and anti-inflammatory properties of Abacopterin A (APA), a flavonoid compound isolated from Abacopteris penangiana (Hook.) Ching. Male C57BL/6J mice were divided randomly and equally into five groups: the normal control group (N), the model group (M), the positive control group (P), the high and low doses of APA treated groups (H and L). All the animals except that in N group were fed with high-fat diet for 8weeks. In the last 4weeks, the mice in P, H and L groups were orally administered with simvastatin (at the dose of 20mg/kg/day) and APA (at the dose of 40 or 20mg/kg/day), respectively. Then the lipid profiles and related biochemical criterions of the studied mice were determined. The effects of high-fat diet on activating nuclear transcription factor-κB (NFκB) expression, elevating inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, and increasing triacylglycerol (TG) and total cholesterol (TC) levels were abolished on daily supplementation with APA. APA also enhanced lipoprotein lipase (LPL) and hepatic lipase (HL) activities. These results suggested that APA had hypolipidemic and anti-inflammatory properties through inhibiting NFκB expression, and reducing inflammatory response.

Enhancement of Lipid Metabolism and Antioxidant Defense Status in Mice Fed with High Fat Diet Supplemented with Antheraea pernyi Silk Fibroin Powder

The effect of diet supplementation of Antheraea pernyi (A. pernyi) silk fibroin on the lipid metabolism and antioxidant defense status in high fat-fed mice was investigated. The animals were given normal control diet (NC group), high fat diet (HF group), or high fat diet supplemented with A. pernyi silk fibroin powder (HFS group) for 7 weeks. After the experimental period, the HF group showed significant increase in body weight, plasma and hepatic total cholesterol levels, and hepatic triglyceride concentration, and decreased activities of hepatic antioxidant enzymes relative to NC group. However, the HFS group exhibited marked reduction in body weight, plasma cholesterol and hepatic triglyceride levels, hepatic lipogenic enzyme activities, and lipid peroxidation rate, and higher high-density lipoprotein (HDL)-cholesterol level, fecal triglyceride content, and antioxidant enzymes activities compared with that of HF group. These findings demonstrate that dietary feeding of A. pernyi silk fibroin could improve the lipid metabolism and antioxidant defense system via regulation of hepatic antioxidant and lipogenic enzymes activities. Hence, this silk fibroin may be beneficial as a functional biomaterial for the development of therapeutic agent against high fat diet-induced hyperlipidemia and its related diseases.

Antihyperlipidemic and Body Fat-Lowering Effects of Silk Proteins with Different Fibroin/Sericin Compositions in Mice Fed with High Fat Diet

The effect of silk protein with different fibroin/sericin compositions on body weight and lipid metabolism in high fat-fed mice was investigated. The animals were given experimental diets for 6 weeks: normal control (NC), high fat (HF) and high fat diet supplemented with F100 (pure fibroin, HF-F100), F81 (81:19 fibroin/sericin, w/w, HF-F81) or F50 (50:50 fibroin/sericin, w/w, HF-F50). The silk protein-fed mice showed markedly reduced body weight and enhanced lipid profile relative to the HF group. In general, the amount of body fat, triglyceride and total plasma cholesterol levels, atherogenic index and free fatty acid level tended to decrease, while the HDL-cholesterol level increased, with increased amount of sericin in the diet. This hypolipidemic effect was partly due to increased fecal lipid excretion, inhibition of lipogenesis and regulation of adipokine production. These findings illustrate that silk protein, particularly sericin, may be beneficial in the prevention of high fat diet-induced hyperlipidemia and obesity.

Lipid-lowering and antioxidant activities of Jiang-Zhi-Ning in Traditional Chinese Medicine

Jiang-Zhi-Ning (JZN) is composed of four Chinese herbs, i.e., Fleeceflower Root, Fructus Crataegi, Folium Nelumbinis and Semen Cassiae. It was used to strengthen blood circulation of coronary artery, arrhythmia and hyperlipidemia. The main objective of this paper is to evaluate lipid-lowering and antioxidant activities of extract and effective fraction of JZN by using in vitro experiments on hyperlipidemic rats. Moreover, in vivo experiments on cells were performed to investigate lipid-lowering and antioxidant activities of effective fraction and active constituents of JZN. Wistar rats with high fat diet-induced hyperlipidemia were used as in vitro models to study biological effects of lipid-lowering and antioxidant activities of extract and effective fraction of JZN. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Coronary Index and Atherogenic Index were investigated to evaluate lipid-lowering effects of extract and effective fraction of JZN. Serum total nitric oxide synthase (NOS), nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were detected to measure antioxidant effects of extract and effective fraction of JZN. Furthermore, oxidized low-density lipoprotein (Ox-LDL) injured human umbilical vein endothelial cell (HUVEC) model was employed as in vivo experiment to study lipid-lowering and antioxidant effects of effective fraction and active constituents of JZN. NO, ET-1, MDA SOD and T-AOC in HUVECs or culture media were investigated to evaluate antioxidant activity of effective fraction and active constituents of JZN. Using human hepatoma cell line Bel-7402, reverse transcription polymerase chain reaction (RT-PCR) technology was performed to investigate cholesterol metabolism effects of effective fraction and active constituents of JZN. Expressions of low density lipoprotein receptor (LDL-R), 3-hydroxy-3-methyl-HMG-coenzyme A reductase (HMG-CoAR), and cholesterol 7α-hydroxylase (CYP7A1) mRNA of the liver cells were investigated to evaluate JZN on associated receptor and enzymes of cholesterol metabolism. High-performance liquid chromatography (HPLC) and spectrophotometry were used to study the impact of effective fraction and active constituents of JZN on synthesis and translation of cholesterol during the process of metabolism by measuring inside and extracellular contents of total bile acid (TBA) of Bel-7402. Extract and effective fraction of JZN significantly reduced contents of TC, TG and LDL-C, CRI and AI in hyperlipidemic rats as well as significantly increased contents of HDL-C in the rats. Moreover, they significantly enhanced the activity of NOS and increased contents of NO. They also caused significant reductions in contents of ET-1 and MDA as well as significant increase in SOD activity and T-AOC in the hyperlipidemic rats. Several indicators were found to be concentration-dependent. As far as in vivo experiments to investigate biological activities of effective fraction and active constituents of JZN were concerned, it was found that they restored and enhanced the vitality of HUVECs with a concentration-dependent manner as well as content of NO in the culture media of HUVEC. They caused reductions in the contents of ET-1 in the culture media of HUVEC and contents of MDA in HUVECs. They also caused an increase in the vitality of SOD and T-AOC in HUVECs. Furthermore, they enhanced LDL-RmRNA expression, with a concentration-dependent manner. Low and medium concentrations of effective fraction and active constituents of JZN could inhibit expression of HMG-CoAR mRNA. High concentration counterpart could enhance expression of the HMG-CoAR mRNA. They enhanced expression of CYP7A1 mRNA in a concentration-dependent manner. Finally, they caused reductions in the contents of cholesterol in Bel-7402. They also increased intercellular content of total bile acid as well as lowered extracellular contents of TBA in the cells in a concentration-dependent manner. We demonstrated for the first time lipid-lowering and antioxidant activities of extract and effective fractions as well as active constituents of JZN. Active constituents of JZN had the same biological effects with effective fraction and extract of JZN. Therefore, this study supports its ethnopharmacological use in Traditional Chinese Medicine to manage hyperlipidemia and paves a basis for establishing quality control method of Chinese medicine.

Ginseng Leaf Extract Prevents High Fat Diet-Induced Hyperglycemia and Hyperlipidemia through AMPK Activation

This study evaluated the protective effects of ginseng leaf extract (GLE) against high fat-diet-induced hyperglycemia and hyperlipidemia, and explored the potential mechanism underlying these effects in C57BL/6J mice. The mice were randomly divided into four groups: normal control, high fat diet control (HFD), GLE-treated at 250 ㎎/㎏, and GLE-treated at 500 ㎎/㎏. To induce hyperglycemic and hyperlipidemic states, mice were fed a high fat diet for 6 weeks and then administered GLE once daily for 8 weeks. At the end of the treatment, we examined the effects of GLE on plasma glucose, lipid levels, and the expression of genes related to lipogenesis, lipolysis, and gluconeogenesis. Both GLE groups lowered levels of plasma glucose, insulin, triglycerides, total cholesterol, and non-esterified fatty acids when compared to those in HFD group. Histological analysis revealed significantly fewer lipid droplets in the livers of GLE-treated mice compared with HFD mice. To elucidate the mechanism, Western blots and RT-PCR were performed using liver tissue. Compared with HFD mice, GLE-treated mice showed higher levels of phosphorylation of AMP-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase, but no differences in the expression of lipogenic genes such as sterol regulatory element-binding protein 1a, fatty acid synthase, sterol-CoA desaturase 1 and glycerol-3-phosphate acyltransferase. However, the expression levels of lipolysis and fatty acid uptake genes such as peroxisome proliferator-activated receptor-α and CD36 were increased. In addition, phospho-α and CD36 were increased. In addition, phosphoenolpyruvate carboxykinase gene expression was decreased. These results suggest that GLE ameliorates hyperglycemia and hyperlipidemia by inhibiting gluconeogenesis and stimulating lipolysis, respectively, via AMPK activation.

Hypotensive, hypolipidemic, and vascular protective effect of Morus alba L. in rats fed a high‐fat diet

Morus alba L. has been used in traditional Chinese medicine and almost all parts of this plant is useful in cardiovascular, liver and spleen disorders. Present study was designed to investigate the inhibitory effect of a water extract from Morus alba L. (WMA) on vascular dysfunction in rat models fed a high‐fat diet. Male rats were fed a high‐fat diet consisting of 60 kcal% fat, with or without 100, 200 mg/day/kg WMA of diet, for 9 weeks. Chronic treatment with low (100 mg/kg/day) or high (200 mg/day/kg) doses of WMA markedly significantly attenuated hypertension and the impairments of acetylcholine‐ and SNP‐induced relaxation of aortic rings in rats fed a high‐fat diet. WMA attenuated plasma levels of triglyceride (TG) and augmented plasma level of high‐density lipoprotein (HDL), whereas, no effects in blood glucose levels and plasma low‐density lipoprotein (LDL) levels in rats fed a high‐fat diet. Interestingly, WMA suppressed increased cell adhesion molecules such as intracellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and E‐selectin expression in aorta. Taken together, these results suggested that Morus alba L. could improve high‐fat diet‐induced hypertension, hyperlipidemia, and vascular dysfunction through inhibition of cell adhesion molecules expression and induction of vascular relaxation.relaxation.

Antioxidant effect of Triticum aestivium (wheat grass) in high-fat diet-induced oxidative stress in rabbits

Wheat grass is used as a general health tonic and is reported to be effective against several medical disorders, although detailed literature is not available. Besides drug therapy, a number of medicinal plants are effective in treating hyperlipidemia. This study examined the effects of wheat grass on high-fat diet-induced hyperlipidemia in rabbits. Thirty rabbits were divided into 3 groups of 10 rabbits each, group I receiving a control diet, group II a high-fat diet and group III a high-fat diet together with wheat grass over a period of 10 weeks. Fasting serum samples from the animals were analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), reduced glutathione (GSH) and vitamin C, and the results were compared. The high-fat diet resulted in hyperlipidemia and an increase in oxidative stress, indicated by a significant rise in MDA levels, whereas antioxidant levels of GSH and vitamin C were significantly reduced. Wheat grass supplementation with a high-fat diet resulted in improved lipid levels (decreased total cholesterol and increased HDL-C) together with significantly reduced MDA levels and increased GSH and vitamin C levels. These results indicate the beneficial role of wheat grass in ameliorating hyperlipidemia and the associated oxidative stress.