High-fat Diet-induced Hyperlipidemic Rats Research Articles

Akebia Saponin D Regulates the Metabolome and Intestinal Microbiota in High Fat Diet-Induced Hyperlipidemic Rats.

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.

Nanocurcumin Preparation for Reducing Vcam-1 and IL-6 in High Fat Diet-Induced Hyperlipidemic Rats

Hyperlipidemia is a pathological condition due to lipid metabolism abnormalities. Increased and oxidized LDL in hyperlipidemia will trigger an inflammatory response and produce proinflammatory cytokines, such as vascular cell adhesion molecule-1 (VCAM-1) and Interleukin-6 (IL-6). Curcumin can be used as antioxidants, anti-inflammatory and antihyperlipidemia, but as it is practically insoluble in water, formulation of curcumin nanosuspension is made to improve the effects of curcumin therapy. This study was conducted to determine the activities of nanocurcumin preparation as preventive measures for rats induced with hyperlipidemia. The test animals used were 49 male Wistar rats divided into 7 test groups: normal control group, negative control group, 80mg/kg BW/day curcumin control group, and nanosuspension curcumin dose of 80mg/kg BW/day, nanoemulsion curcumin dose of 80mg/kg BW/day, SNEDDS curcumin dose of 80mg/kg BW/day and solid lipid nanoparticles dose of 80mg/kg BW/day. Provision of preventive measure was performed on days 1-67. On day 11-67, the induction of lard and egg yolk (1:1) was administered with a volume of 2mL/200g of rat BW. On the 68 th day, blood samples were taken for the determination of VCAM-1 and IL-6 parameters using Biotin-Streptavidin-Amplified Enzyme-Linked Immuno-sorbent Assay method. Data analysis of VCAM-1 and IL-6 levels between test groups were conducted by means of normality test and One-way ANOVA (p<0.05). Based on the data of VCAM-1 and IL-6 levels, nanocurcumin dose of 80mg/kg BW preparation was able to significantly improve the preventive activity of curcumin compared to curcumin suspension dose of 80mg/kg BW by reducing VCAM-1 levels in SNEDDS (53.260%), nanoemulsion (52.737%), nanosuspension (52.325%) and solid lipid nanoparticles (51.444%) and decreasing IL-6 levels in SNEDDS (33.030%), nanoemulsion (31.568%), nanosuspension (29.898%), and solid lipid nanoparticles (28.875%).

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.

Antilipidemic properties of Calpurnia aurea leaf extract on high-fat diet induced hyperlipidemia

Background: Hyperlipidemia is described by raised in the plasma lipids including triglycerides (TG), cholesterols, cholesterol esters, phospholipids as well as plasma lipoproteins, for example, very low-density lipoprotein (LDL), LDL, and reduction in the circling high-density lipoprotein (HDL) levels. Objective: To explore the antilipidemic properties of the hydromethanolic extract of Calpurnia aurea (HMECA) leafs against high-fat diet-induced hyperlipidemic male albino Wistar rats. Materials and Methods: Thirty albino Wistar rats of 60–75 days and weights of 150–200 g were isolated arbitrarily into six groups of five each. Group I fed with normal diet in as typical control, Group II got high-fat-eating routine (48.8% fat w/w) containing fat produced using hamburger fat and blended with hydrogenated vegetable oil, Group III fed with high fat diet plus 3.5 mg/kg/day atorvastatin as standard control, and the remaining Groups IV, V, and VI fed with high fat diet along with different does of HMECA at 200, 300, and 400 mg/kg/day separately for 60 days. Food intake, body weight, body mass index, serum lipid profiles, and liver histopathology were studied. Results: The results of this investigation exposed that HMECA has dose-dependent antilipidemic exercises. HMECA treatment of 400 mg/kg caused a noteworthy bringing down of P

Aqueous extract of Garcinia atroviridis fruit improves oxidative status of high fat diet-induced hyperlipidemic rats

Aqueous extract of Garcinia atroviridis fruit improves oxidative status of high fat diet-induced hyperlipidemic rats

Lipid-lowering effect of hydroalcoholic extracts of Gynura procumbens in Chemical- and High-fat diet-induced hyperlipidemic rats

Objective: The present study was carried out to investigate lipid-lowering effect of hydroalcoholic extracts of Gynura procumbens in chemical- and high-fat diet (HFD)-induced hyperlipidemic rats. Materials and Methods: The lipid-lowering effect of hydroalcoholic extracts was investigated in poloxamer-407 (P-407)-induced acute hyperlipidemic rat model. The most active extract was subjected to phytochemical analysis by high-performance liquid chromatography-ultraviolet (HPLC-UV) using phenolic acids as marker compounds and evaluated in HFD-induced chronic hyperlipidemic rats. Results: The evaluation on hydroalcoholic extracts of G. procumbens showed that 95% ethanolic extract (95EEGP) was the most potent extract that significantly reduced serum total cholesterol (TC, P < 0.05) and triglycerides (TG, P < 0.001) levels. The 95EEGP contained 7.18, 3.20, 28.31, and 9.72 mg/g dried extract of chlorogenic acid (CA), 3,4-dicaffeoylquinic acid (3,4DC), 3,5DC, and 4,5DC, respectively. The extract at doses of 200 and 500 mg/kg significantly reduced serum TC, TG, low-density lipoprotein-cholesterol (LDL-C), and atherogenic index (A. I.) levels of the P-407-induced hyperlipidemic rats, in a dose-dependent manner (P < 0.01 or better) but had no effect on high-density lipoprotein-cholesterol (HDL-C). On HFD-induced hyperlipidemic rats, the 95EEGP at doses of 250, 500, and 1000 mg/kg significantly reduced the serum TC, TG, LDL-C, and A. I. levels (P < 0.05 or better) while increased serum HDL-C (P < 0.001). The effect was dose-dependent showing comparable effect to that of atorvastatin at moderate and high doses. Conclusion: The present study demonstrated the lipid-lowering potential of the 95EEGP of G. procumbens in chemical- and HFD-induced hyperlipidemic rat models. Further investigations are warranted to elucidate its mechanism of its lipid-lowering action. Abbreviations used: HFD, high-fat diet; P-407, poloxamer-407; 95EEGP, 95% ethanolic extract; TC, total cholesterol; TG, triglycerides; 3,4DC, 3,4-dicaffeoylquinic acid; 3,5DC, 3,5-dicaffeoylquinic acid; 4,5DC, 4,5-dicaffeoylquinic acid; LDL-C, low-density lipoprotein-cholesterol; A. I., atherogenic index; HDL-C, high-density lipoprotein-cholesterol; CVD, cardiovascular disease; HMG CoA, 3-hydroxy-3-methylglutaryl coenzyme A; G. procumbens, Gynura procumbens; HPLC-UV, high-performance liquid chromatography-ultraviolet; CA, chlorogenic acid; 75EEGP, 75% ethanolic extract; 50EEGP, 50% ethanolic extract; 25EEGP, 25% ethanolic extract; AEGP, water extract; MeOH, methanol; SEM, standard error mean; VLDL-C: Very low-density lipoprotein-cholesterol.

Experimentally designed lyophilized dry emulsion tablets for enhancing the antihyperlipidemic activity of atorvastatin calcium: Preparation, in-vitro evaluation and in-vivo assessment

This article presents the development of lyophilized orally disintegrating tablets prepared with the dry emulsion technique to enhance the in-vitro dissolution and in-vivo performance of the poorly bioavailable drug atorvastatin calcium (ATV). Tablets were fabricated by freeze-drying o/w emulsions of ATV. The Emulsions were prepared using a matrix former solution (alginate or gelatin, 2 or 4%) containing a sugar alcohol (mannitol) and a collapse protectant (glycine) as the water phase and Labrafac® as the oil phase in the presence of surfactant (synperonic® PE/P 84 or synperonic® F108) under proper homogenization. The influence of formulation parameters on friability of the prepared tablets, disintegration time and in-vitro dissolution of the drug from these tablets were investigated. Results showed the significant influence of the matrix former and emulsifier type on the disintegration time. In-vitro dissolution study revealed the enhanced dissolution rate of ATV from the lyophilized dry emulsion tablets (LDET) compared to the plain drug. DSC and XRD studies of the optimized ATV-loaded LDET proved the presence of the drug in the amorphous form. SEM images showed the intact, porous and non-collapsible structure of the prepared LDET with complete loss of ATV crystallinity. Administration of ATV-loaded LDET to high fat diet-induced hyperlipidemic rats demonstrated a significant decrease (p<0.05) in the serum and tissue levels of the tested parameters compared to the market product used. The obtained results suggest a promising, easy-to-manufacture and effective dosage form for the treatment of hyperlipidemia.

Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats

Context: Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. Objective: The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. Materials and methods: Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively. Results: ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold). Conclusions: ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats. These activities were closely correlated with ASTX, maintaining the balance of t-PA/PAI-1, NO/ROS and TXA2/PGI2 in vivo.

Antihyperlipidemic effect of Ficus dalhousiae miq. stem bark on Triton WR-1339 and high fat diet-induced hyperlipidemic rats

Ficus dalhousiae stem bark is used to treat cancer and hyperlipidemia in folklore practices. F. dalhousiae stem bark methanolic extract (250 and 500mg/kgb. wt.) was evaluated for antihyperlipidemic activity in Triton WR-1339 and high fat diet-induced hyperlipidemic rats. F. dalhousiae extract significantly (P⩽0.005) alter the serum TC, TG, LDL-C and HDL-C levels to near normal in Triton WR-1339 and high fat diet-induced hyperlipidemic rats. The liver total cholesterol and triglycerides were also significantly reduced after treatment with 250 and 500mg/kg of F. dalhousiae. The result of this study indicates that F. dalhousiae has a significant potential to use as a natural antihyperlipidemic agent.

Antihyperlipidemic and Antioxidant Activities of Edible Tunisian Ficus carica L. Fruits in High Fat Diet-Induced Hyperlipidemic Rats.

The phenolic constituents of the aqueous-ethanolic extract of Tunisian Ficus carica (F. carica) fruit (FE) and its antihyperlipidemic and antioxidant activities in high-fat diet-induced hyperlipidemic rats (HFD) were evaluated. The obtained results demonstrated that the FE improved the lipid profile by decreasing the total cholesterol, triglyceride, low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol levels. It also reduced the content of thiobarbituric acid-reactive substances and increased the antioxidant enzymes in liver, heart and kidney in HFD-fed rats. These antihyperlipidemic effects and in vivo antioxidative effects correlated with the in vitro phenolic content scavenging ability. Thus, the major phenolic compounds were identified using reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled with two detection systems: diode-array detection (DAD) and quadrupole time-of-flight (QTOF) mass spectrometry (MS). Therefore, in the negative ionization mode, 28 phenolic compounds, including hydroxybenzoic acids, hydroxycinnamic acids, flavanoids and hydroxycoumarins were characterized. Dihydroxybenzoic acid di-pentoside, the flavonol quercetin 3-O-rutinoside and the flavone assigned as apigenin 8-C-glucoside were the main representative compounds in 'Tounsi' fruits. This work was complemented by the detection of seven other phenolic compounds in the positive ionization mode, including anthocyanins and furanocoumarins. Overall, these results have shown that the FE has a significant hypocholesterolemic effect and antioxidant activity in HFD-fed rats. This beneficial effect may be partly due to these phenolic constituents, especially vitexin, dihydroxybenzoic acid di-pentoside as well as rutin.

Evaluation of physicochemical properties and in vivo efficiency of atorvastatin calcium/ezetimibe solid dispersions

Fixed-dose combination of atorvastatin calcium (ATV) and ezetimibe (EZT) provides a considerable advantage in the management of hyperlipidemia. However, both ATV and EZT suffer from the poor aqueous solubility, which can limit their oral bioavailability. The aim of the present study was to improve the in vitro performance and evaluate the in vivo efficiency of the improved (ATV/EZT) fixed-dose combination. The formulation was prepared through solid dispersion (SD)technique, using Polyvinylpyrrolidone K30 via solvent method. Solid-state analysis and the in vitro drug release of the prepared formulations were also assessed. In order to estimate the therapeutic efficiency of the prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were conducted. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that the drugs crystallinity was notably decreased during the preparation process. All SDs showed enhanced release for both drugs compared to their binary mixture, drugs: polymer physical mixtures (PMs) and marketed product. Administration of ATV/EZT SD led to a remarkable decrease (P<0.05) in the serum levels of total cholesterol (TC) and LDL-C in the high fat diet-induced hyperlipidemic rats compared to the PM. Additionally, the histopathological examination of the liver tissue revealed the improved efficiency of the SDs on the liver steatosis. According to the obtained results, ATV/EZT SD with improved physicochemical characteristics, showed favorable effects on the serum lipid levels and liver steatosis.

Hypolipidemic activity of friedelin isolated from Azima tetracantha in hyperlipidemic rats

The hypolipidemic activity of friedelin isolated from Azima tetracantha Lam., Salvadoraceae, was studied in Triton WR-1339 and high-fat diet-induced hyperlipidemic rats. In Triton WR-1339 induced hyperlipidemic rats, treatment with friedelin (50 and 70mg/kg) showed a significant (p<0.01) lipid-lowering effect as assessed by reversal of plasma levels of total cholesterol (TC), triacylglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). In high-fat diet fed hyperlipidemic rats, treatment with friedelin (50 and 70mg/kg) caused lowering of lipid levels in plasma and liver. The hypolipidemic activity of friedelin was compared with fenofibrate, a known lipid-lowering drug, in both models.

Physicochemical characterization and pharmacological evaluation of ezetimibe-PVP K30 solid dispersions in hyperlipidemic rats

The aim of this study was to improve the physicochemical properties as well as therapeutic efficacy of ezetimibe (EZT), through preparation of the solid dispersion (SD). SDs were formulated using polyvinylpyrrolidone K30 (PVP) via solvent method. The physicochemical properties along with in vitro drug release patterns of the prepared SDs were examined. To estimate the therapeutic efficiency of prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were performed. Differential scanning calorimetry (DSC) and powder X-ray diffractometery (PXRD) showed that the drug crystallinity was remarkably decreased during preparation process. Faster drug release pattern of SDs was proved by in vitro dissolution test. Administration the SD of EZT led to a significant decrease in serum total cholesterol (TC) and LDL-C level as well as liver index in hyperlipidemic rats (P<0.05) compared to the PM. Furthermore, histological analysis of the liver tissue confirmed the improved efficacy of the SDs on the liver steatosis. In the present study, we demonstrated that the SDs of EZT with improved physicochemical characteristics had favorable effects on liver steatosis, liver index and serum lipid levels in the high fat diet-induced hyperlipidemic rats.

N-Acetylneuraminic acid attenuates hypercoagulation on high fat diet-induced hyperlipidemic rats

Background and objectiveN-Acetylneuraminic acid (Neu5Ac), a type of sialic acid, has close links with cholesterol metabolism and is often used as a biomarker in evaluating the risk of cardiovascular diseases. However, most studies on the health implications of Neu5Ac have focused on its effects on the nervous system, while its effects on cardiovascular risk factors have largely been unreported. Thus, the effects of Neu5Ac on coagulation status in high fat diet (HFD)-induced hyperlipidemic rats were evaluated in this study.MethodsSprague Dawley male rats were divided into five different groups and fed with HFD alone, HFD low-dose Neu5Ac, HFD high-dose Neu5Ac, HFD simvastatin (10 mg/kg day), and normal pellet alone. Food was given ad libitum while body weight of rats was measured weekly. After 12 weeks of intervention, rats were sacrificed and serum and tissue samples were collected for biochemistry and gene expression analysis, respectively.ResultsThe results showed that Neu5Ac could improve lipid metabolism and hyperlipidemia-associated coagulation. Neu5Ac exerted comparable or sometimes better physiological effects than simvastatin, at biochemical and gene expression levels.ConclusionsThe data indicated that Neu5Ac prevented HFD-induced hyperlipidemia and associated hypercoagulation in rats through regulation of lipid-related and coagulation-related genes and, by extension, induced metabolite and protein changes. The implications of the present findings are that Neu5Ac may be used to prevent coagulation-related cardiovascular events in hyperlipidemic conditions. These findings are worth studying further.

자귀나무와 결명자 추출 혼합물의 항고지혈 효과

본 연구에서는 자귀결명자추출혼합물 첨가사료의 혈청 콜레스테롤 저하효과를 확인하기 위하여 3주령된 SD계 수컷흰쥐를 실험군당 12마리씩 배치하여 10주 동안 동물실험을 수행하였다. 흰쥐용 사료(AIN-93G diet, 조지방 함량 7%)를 기본식이로 하여 돈지와 콜레스테롤을 각각 중량비로 7%, 1% 첨가하여 총지방함량이 15%가 되도록 고지방식이를 제조하였다. 흰쥐에게 실험 1기 (first phase) 5주 동안 고지방식이(high-fat diet)를 급여하여 고지혈증을 유발시켰다. 실험 2기(second phase)에는 고지방식이군을 대조군으로 하고, 자귀결명자추출혼합물 분말을 1.0, 2.5, 5.0, 10% 첨가군으로 하여 5주 동안 급여하였다. 자귀결명자추출혼합물 첨가사료(1.0, 2.5, 5.0%)는 고지방식이를 급여한 흰쥐의 배변량을 유의하게 증가시켰고, 체지방중 EFP 무게는 시료 첨가군(10%)에서 유의하게 감소하였다. 혈청 지질중 총콜레스테롤 농도는 시료첨가군(5.0, 10%)이 유의하게 낮았고, HDL-콜레스테롤 농도는 시료 첨가군(1.0%)이 가장 높았다. 중성지방농도는 고지방식이 대조군에 비해 시료 첨가군(2.5% 5.0, 10%)에서 낮은 경향인 것으로 나타났다. 간조직의 효소활성에서 G6PDH 활성은 고지방식이 대조군보다 모든 시료 첨가군에서 유의하게 감소한(p<0.05), 반면 malic enzyme 활성은 고지방식이 대조군에 비하여 시료 첨가군(1.0, 10%)이 유의하게 감소하였다. 이 결과들을 종합해보면, 고지혈증 흰쥐에서의 자귀결명자추출혼합물 분말은 전반적인 지질대사 개선에 긍정적인 효과를 나타냄으로써 앞으로 고콜레스테롤혈증 예방 등의 혈관 순환기 계통 질병을 예방하기 위한 식품으로서의 활용이 기대된다. The present study was undertaken to evaluate the anti-hyperlipidemic activity of Albizzia julibrissin and Cassia tora L. extract mixtures in high fat diet-induced hyperlipidemic rats. In high-fat diet fed hyperlipidemic rats, oral treatment with Albizzia julibrissin and Cassia tora L. extracts resulted in decreased levels of total serum cholesterol and triglycerides, epididymal fat pad (EFP) weights, and activities of hepatic glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme, while the levels of feces production and high-density lipoprotein (HDL)-cholesterol were increased, compared with untreated control. Therefore, these results suggest that Albizzia julibrissin and Cassia tora L. extract mixtures can ameliorate hyperlipidemia.

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

BACKGROUNDGroundwater is believed to possess many beneficial effects due to its natural source of various minerals. In this study, we examined the effects of natural Jeju groundwater S1 (Samdasoo™), S2 and S3 pumped up from different locations of Jeju Island, Korea, along with local tap water, on body weight gain, serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced hyperlipidemic rats.MATERIALS/METHODSRats were randomly and equally divided into 6 groups. Different water samples were supplied to the hyperlipidemic rats as their daily drinking water and the widely-used anti-hyperlipidemic drug simvastatin was used as a positive control. Body weight, serum lipids and lipoproteins were measured weekly. Liver weight, liver index and liver histopathology were examined after the execution of the rats.RESULTSAfter drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced weight growth and serum triglycerides levels and increased high density lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and particularly S2 significantly reduced the severity of liver hypertrophy and steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous ions.CONCLUSIONJeju Groundwater S1 and particularly S2 exhibit protective effects against hyperlipidemia and fatty liver and hypothesize that the beneficial effect of Jeju Groundwaters may be contributed from blockade of autoxidation of ferrous ions rather than their high contents of vanadium.

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

Activation of transsulfuration pathway by salvianolic acid a treatment: a homocysteine-lowering approach with beneficial effects on redox homeostasis in high-fat diet-induced hyperlipidemic rats

BackgroundElevated homocysteine is a cardiovascular risk factor in hyperlipidemia. Transsulfuration pathway provides an endogenous pathway for homocysteine conversion to antioxidant glutathione (GSH). Salvianolic acid A (Sal A) contains two molecules of caffeic acid and one molecule of danshensu that is capable of enhancing homocysteine transsulfuration, which led to the hypothesis that Sal A has activatory effect on transsulfuration pathway and this effect may have beneficial effects on both homocysteine and redox status in hyperlipidemia.Methods and resultsTo test this hypothesis, we developed a rat model of hyperlipidemia induced by high-fat diet for 16 weeks, during which rats were treated with 1 mg/kg salvianolic acid A (Sal A) for the final 4 weeks. Activities of key enzymes and metabolite profiling in the transsulfuration pathway revealed that hyperlipidemia led to elevated plasma homocysteine levels after 16-week dietary treatment, which was associated with reduced activities of homocysteine transsulfuration enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). The impaired transsulfuration pathway prevented homocysteine transsulfuration to cysteine, resulting in cysteine deficiency and subsequent reduction in GSH pool size. The redox status was altered in the setting of hyperlipidemia as indicated by GSH/GSSG ratio. Sal A treatment increased hepatic CBS and CSE activities, which was associated with reduced accumulation in circulating homocysteine levels and attenuated decline in hepatic cysteine content in hyperlipidemic rats. Sal A also led to an increase in GSH pool size, which subsequently caused a restored GSH/GSSG ratio. The activatory effect of Sal A on CBS was also observed in normal rats and in in vitro experiment.ConclusionOur results suggest that activation of transsulfuration pathway by Sal A is a promising homocysteine-lowering approach that has beneficial effects on redox homeostasis in hyperlipidemic settings.

In vitro antioxidant and antihyperlipidemic activities of Toddalia asiatica (L) Lam. Leaves in Triton WR-1339 and high fat diet induced hyperlipidemic rats

The present study was undertaken to evaluate the in vitro antioxidant and antihyperlipidemic activity of Toddalia asiatica (L) Lam. leaves in Triton WR-1339 and high fat diet-induced hyperlipidemic rats. In in vitro studies T. asiatica leaves ethyl acetate extract showed very good scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC₅₀ 605.34±2.62 μg/ml), hydroxyl (IC₅₀ 694.37±2.12 μg/ml) and nitric oxide (IC₅₀ 897.83±1.48 μg/ml) radicals, as well as high reducing power. In Triton WR-1339 induced hyperlipidemic rats, oral treatment with T. asiatica leaves ethyl acetate extract produced a significant (P≤0.005) decrease in the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), and significant increase in high-density lipoprotein cholesterol (HDL-C) in comparison with hexane and methanol extracts. In high fat diet-fed hyperlipidemic rats, the ethyl acetate extract (200 and 400 mg/kg) significantly altered the plasma and liver lipids levels to near normal.

Hypolipidemic activity of Symplocos cochinchinensis S. Moore leaves in hyperlipidemic rats

The hypolipidemic activity of Symplocos cochinchinensis S. Moore leaves was studied in Triton WR-1339- and high fat diet-induced hyperlipidemic rats. In Triton WR-1339-induced hyperlipidemic rats, the hexane extract (250 and 500 mg/kg) exerted a significant (P < 0.01) lipid-lowering effect compared to ethyl acetate and methanol extracts, as assessed by the reversal of the plasma levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). In high fat diet-fed hyperlipidemic rats, the hexane extract (250 and 500 mg/kg) caused the lowering of lipid levels in the plasma and liver. The hypolipidemic activity of S. cochinchinensis leaves was compared with fenofibrate, a known lipid-lowering drug, in both models.