High-fat Diet-induced Hyperlipidemic Mice Research Articles

Hydroalcoholic Extract of Sechium edule Fruits Attenuates QT Prolongation in High Fat Diet-Induced Hyperlipidemic Mice.

The present study aimed to evaluate the effect of hydroalcoholic extract of Sechium edule (S.E.) fruits on lipid profile and electrocardiogram (ECG) parameters in high fat-diet (HFD) induced hyperlipidemic mice. In this study, grouping of animals was done as described below (n = 6), where group 1 is normal control, group 2 is HFD control, group 3 is HFD + atorvastatin (10 mg/kg), group 4 is HFD + S.E. extract (200 mg/kg), and group 5 is HFD + S.E. extract (400 mg/kg). The first 3 weeks animals were supplemented with HFD, and the last 3 weeks animals were supplemented with HFD along with atorvastatin (10 mg/kg) or S.E. extract (200 and 400 mg/kg). It was observed that mice of the HFD control group showed a significant rise in the total cholesterol, triglycerides, LDL-C, and VLDL-C levels and a notable decrease in HDL-C levels. In addition, a consequential increment in ECG parameters such as QT or QTc and RR interval and a noteworthy decline in the heart rate were observed in HFD control mice. Treatment with S.E. extract (200 and 400 mg/kg) showed a significant improvement in the lipid profile. Moreover, the extract also significantly normalized the prolonged QT or QTc and RR interval and the heart rate in HFD-challenged mice. Hence, we can conclude that S.E. extract encumbers the prolongation of QT or QTc and RR interval and increased the heart rate in HFD-challenged mice.

Lipid-lowering effect of Oroxylum indicum (L.) Kurz extract in hyperlipidemic mice

Objective: To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice. Methods: The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry. Forty-two male mice were used. The mice were divided into six groups: normal control, high-fat diet control, simvastatin treatment (20 mg/kg BW/day), and Oroxylum indicum fruit extract (100, 200, 300 mg/kg BW/day) treatment groups. Food intake, body weight, serum parameters, lipid profile, and histopathological lesions of the kidney, liver, and epididymal fat were observed. Results: LC-MS/MS results revealed four major components of Oroxylum indicum fruit extract: luteolin, apigenin, baicalein, and oroxylin A. Twenty-seven volatile oils were identified from Oroxylum indicum fruit extract. Daily oral administration of Oroxylum indicum fruit extract at 100 to 300 mg/kg BW/day significantly reduced the body weight, total cholesterol, triglyceride, and low-density lipoprotein cholesterol level (P<0.05), whereas high-density lipoprotein cholesterol was higher than the high-fat diet control group. Treatment with 300 mg/kg BW/day Oroxylum indicum fruit extract reduced the pathological lesion and prevented fat accumulation in the kidney and liver. Conclusions: Oroxylum indicum fruit extract has hypolipidemic effect in hyperlipidemic mice, and the active ingredients of Oroxylum indicum fruit extract, both flavonoids and volatile oils, should be further explored as an antihyperlipidemic agent.

Dried mulberry fruit ameliorates cardiovascular and liver histopathological changes in high-fat diet-induced hyperlipidemic mice

Background and aimMetabolic disease encompasses most contemporary non-communicable diseases, especially cardiovascular and fatty liver disease. Mulberry fruits of Morus alba L. are a favoured food and a traditional medicine. While they are anti-atherosclerotic and reduce hyperlipidemic risk factors, studies need wider scope that include ameliorating cardiovascular and liver pathologies if they are to become clinically effective treatments. Therefore, the present study sought to show that freshly dried mulberry fruits (dMF) might counteract the metabolic/cardiovascular pathologies in mice made hyperlipidemic by high-fat diet (HF). Experimental procedureC57BL/6J mice were fed for 3 months with either: i) control diet, ii) HF, iii) HF+100 mg/kg dMF, or iv) HF+300 mg/kg dMF. Body weight gain, food intake, visceral fat accumulation, fasting blood glucose, plasma lipids, and aortic, heart, and liver histopathologies were evaluated. Adipocyte lipid accumulation, autophagy, and bile acid binding were also investigated. Results and conclusionHF increased food intake, body weight, visceral fat, plasma total cholesterol (TC) and low-density lipoprotein (LDL), TC/HDL ratio, blood glucose, aortic collagen, arterial and cardiac wall thickness, and liver lipid. Both dMF doses prevented hyperphagia, body weight gain, and visceral fat accumulation, lowered blood glucose, plasma TG and unfavourable TC/HDL and elevated plasma HDL beyond baseline. Arterial and cardiac wall hypertrophy, aortic collagen fibre accumulation and liver lipid deposition ameliorated in dMF-fed mice. Clinical trials on dMF are worthwhile but outcomes should be holistic commensurate with the constellation of disease risks. Here, dMF should supplement the switch to nutrient-rich from current energy-dense diets that are progressively crippling national health systems.

Phenolic-Rich Extract from Almond (Prunus dulcis) Hulls Improves Lipid Metabolism in Triton WR-1339 and High-Fat Diet-Induced Hyperlipidemic Mice and Prevents Lipoprotein Oxidation: A Comparison with Fenofibrate and Butylated Hydroxyanisole.

Hyperlipidemia and oxidative stress are risk factors for atherosclerosis. In this study, we investigated the hypolipidemic and anti-lipoprotein oxidation activities of polyphenol-rich extracts from almond hulls using Triton WR-1339 and high-fat diet-induced hyperlipemic mice as experimental models. We demonstrated that the almond hull extract significantly reduced total cholesterol, triglycerides and low-density lipoprotein-related plasma cholesterol (LDL-C) in the two experimental models of hyperlipidemia, but significantly increased high-density lipoprotein-related plasma cholesterol (HDL-C). Another beneficial effect of the extract was its ability to reduce the atherogenic index and LDL-C/HDL-C ratio. However, the extract exhibited effective antiradical activity against 2,2-diphenyl-1-picrylhydrazyl and significantly protected lipoprotein-rich plasma from mice against oxidation induced by copper ion. The extract contains 342.63±3.44 mg/g total phenolics, 144.67±6.83 mg/g tannins, and 20.66±0.92 mg/g flavonoids. These finding indicate that almond hulls contain polar products able to lower plasma lipid concentrations and which might be beneficial for the treatment of hyperlipidemia and prevention of atherosclerosis.

Extracellular and Intracellular Polysaccharide Extracts of Trametes versicolor Improve Lipid Profiles Via Serum Regulation of Lipid-Regulating Enzymes in Hyperlipidemic Mice.

Trametes versicolor extracts have been shown to have health-promoting benefits in hypercholesterolemia, obesity, hepatic steatosis, and cardiovascular disease. However, hypolipidemic or the anti-hyperlipidemic effects of polysaccharide extracts of T. versicolor (PTVs) are not yet clear. In present work, the structural characterization of intracellular (IPTV) and the extracellular polysaccharide extracts of T. versicolor (EPTV) were partially clarified, and their effects on serum lipid metabolism and regulation of lipid-regulating enzymes in high-fat diet-induced hyperlipidemic mice were also investigated. Results indicated that IPTV and EPTV are α-pyran polysaccharide with an average molecular weight of 127 and 68.4kDa, respectively, and were mainly composed of mannose, glucose and galactose. In vivo study, EPTV treatment (200mg/kg/d) significantly decreased serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), and atherosclerosis index (AI) of hyperlipidemic mice by 20.97%, 57.85%, 27.72%, and 20.35%, respectively (P < 0.01), while IPTV treatment (100mg/kg/d) showed a significant (P < 0.01) decrease in serum TC (17.05%), TG (43.80%), LDL-C (25.61%) levels, and AI value (13.32%). A significant increase in serum lipoprotein lipase (LPL) activity and decrease in protein expression of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) were observed following EPTV administration, while IPTV remarkably promoted LPL activity. These results suggest that IPTV and EPTV which improve serum lipid profiles in high-fat diet-induced hyperlipidemic mice via mechanisms regulated by serum LPL and hepatic HMGR have potential for further development as novel therapeutic dietary supplements for the prevention and treatment of hyperlipidemia.

Hypolipidemic Effect of Trixis angustifolia Aqueous Extract on Triton WR-1339- and High-Fat Diet-Induced Hyperlipidemic Mice

The aim of the present study was to evaluate the hypolipidemic effect of Trixis angustifolia aqueous extract (TxAE) on Triton WR-1339- and high-fat diet-induced hyperlipidemic mice. In the Triton model, treatment with TxAE at 100 and 200 mg/kg body weight produced a significant decrease in triglycerides and very low-density lipoprotein levels and a significant increase in high-density lipoprotein (HDL). Similarly, administration of TxAE along with the high-fat diet induced a significant decrease in serum total cholesterol, low-density lipoproteins, and increase in HDL. In addition, a phytochemical study of TxAE led to the isolation of 2 previously described compounds: pebrellin and xanthomicrol. This is the first time that these compounds have been identified in a plant extract with hypolipidemic effect. The results suggest the possible therapeutic potential of TxAE as a hypolipidemic agent supporting the usage of T. angustifolia as a traditional medicine.

The metabolic change in serum lysoglycerophospholipids intervened by triterpenoid saponins from Kuding tea on hyperlipidemic mice.

Triterpenoid saponins from Kuding tea have demonstrated preventive effects on hyperlipidaemia induced by a high-fat diet. Lysoglycerophospholipids (Lyso-GPLs) are known to be associated with proatherogenic conditions such as hyperlipidaemia. In this study, a target profiling strategy based on a multiple reaction monitoring mode was applied for the analysis of Lyso-GPLs. The metabolic changes were evaluated by the qualitative and relative quantitative distribution of six classes of Lyso-GPLs in mouse serum. A total of 153 Lyso-GPL regioisomers, consisting of 85 lysophosphatidylcholines, 15 lysophosphatidic acids, 23 lysophosphatidylethanolamines, 5 lysophosphatidylserines, 19 lysophosphatidylinositols and 6 lysophosphatidylglycerols, were detected and quantified. The results showed decreased trends in the content of total Lyso-GPLs in the serum of hyperlipidemic mice compared with that in normal controls. The content of total Lyso-GPLs significantly increased after treatment with triterpenoid saponins from Kuding tea. Among them, the proportions of most Lyso-GPLs with a higher degree of unsaturation or a longer carbon chain in fatty acyl chains dramatically decreased in hyperlipidemic mice. However, this tendency reversed after the treatment of triterpenoid saponins from Kuding tea. This is the first study regarding a target profiling strategy for the quantitative analysis of six different types of Lyso-GPLs on high-fat diet-induced hyperlipidemic mice intervened by Kuding tea. Those Lyso-GPLs changed significantly may be potential biomarkers for hyperlipidaemia, and involved in the mechanism of the preventive intervention of Kuding tea on Lipid metabolic diseases.

Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy.

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1—a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (30 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

Lipid- and gut microbiota-modulating effects of graphene oxide nanoparticles in high-fat diet-induced hyperlipidemic mice.

Graphene oxide (GO) suspensions can act as a good dispersant and drug delivery system for effective dispersion and drug sustained release. In this study, we investigated the impact of GO on blood/liver lipids and gut microbiota structure in high-fat diet (HFD)-induced hyperlipidemic mice. Oral administration of GO for 28 days remarkably decreased the lipid levels in blood and liver. GO did not decrease the total number of gut bacteria but increased the relative abundance of short-chain fatty acid (SCFA)-producing bacteria such as Clostridium clusters IV and Allobaculum spp. GO also enhanced the copying of bacterial butyryl coenzyme A transferase (BcoA), a key butyrate-producing gene. Although further pharmacological studies are still needed, these results provided an interesting hint that GO may exert beneficial effects on the host's metabolism via selective modulation of SCFA-producing gut microbes.

Effect of methanol extract of Salviae miltiorrhizae Radix in high-fat diet-induced hyperlipidemic mice

BackgroundThe dried root of Salvia miltiorrhiza, Salviae miltiorrhizae Radix (SR), is one of the most popular medicinal herbs in Asian countries such as China and Korea. In Asian traditional medicine, SR is considered to have a bitter flavor, be slightly cold in nature, and exert therapeutic actions in the heart and liver meridians. Thus, SR has been used to control symptoms related to cardiovascular diseases. Hyperlipidemia is recognized as the main cause of cerebrovascular and heart diseases; consequently, therapeutic strategies for hyperlipidemia have been widely studied. In this study, the effects and molecular targets of methanol extract of SR (SRme) in hyperlipidemic mice were investigated.MethodsHigh-fat diet was fed to mice to induce hyperlipidemia, and measurement of blood cholesterol and triglycerides were conducted to evaluate the effect of SRme on hyperlipidemic mice, and gene expression in mice liver was analyzed to identify key molecules which could be potential targets for developing anti-hyperlipidemic herbal medicines.ResultsThere was no significant effect on the body weight gain of hyperlipidemic mice, but the triglyceride content in blood was significantly reduced by the administration of SRme to hyperlipidemic mice. Proteins such as minichromosome maintenance (Mcm) family which play a key role in DNA replication were identified as molecular targets in the amelioration of hyperlipidemia.ConclusionsSRme ameliorated hyperlipidemia in high-fat diet fed mice by inhibiting increase of blood serum level of triglycerides. And several proteins such as Mcm proteins were deduced to be molecular targets in treating hyperlipidemia.

The Hypolipidemic Effect of Total Saponins from Kuding Tea in High-Fat Diet-Induced Hyperlipidemic Mice and Its Composition Characterized by UPLC-QTOF-MS/MS.

Kuding tea are used as a traditional tea material and widely consumed in China. In this study, total saponins (TS) from water extract of Kuding tea was prepared by D101 macroporous resins and analyzed by UPLC-QTOF-MS/MS. Then the hypolipidemic effect of TS extract was investigated in high-fat diet-induced hyperlipidemic mice. For comprehensive identification or characterization of saponins in TS extract, 3 major saponins of Kudinoside A, Kudinoside F, and Kudinoside D were isolated and used as standards to investigate the MS/MS fragmentation pattern. As a result, 52 saponins were identified or characterized in TS extract from Kuding tea. In addition, the increased levels of mice serum TC, LDL-C, HDL-C, and atherogenic index (AI) were significantly reduced after the treatment of TS extract. Also, the liver protective effect of TS extract was obviously judged from the photographs stained with oil red-O staining. Meanwhile, TS extract significantly upregulated the expression of hepatic scavenger receptors including SR-AI, SR-BI, and CD36. Therefore, it is reasonable to assume that the overexpression of hepatic scavenger receptors was involved in the hypolipidemic effect of Kuding tea on the high-fat diet-induced hyperlipidemic mice. The TS extract could influence these scavenger receptors, and this could be the potential mechanism of TS extract from Kuding tea in the treatment of lipid disorders. These results give the evidence that the saponins in Kuding tea could provide benefits in managing hypercholesterolemia and may be a good candidate for development as a functional food and nutraceutical.

金錢草 추출물이 고지방 식이에 의한 생쥐의 지질 대사 변화에 미치는 영향

Objectives : Herba on lipid levels in serum and lipid accumulation in liver tissue in high fat diet-induced hyperlipidemic mice. Methods : Experimental groups were subdivided into four; Normal diet group (Nor), Hyperlipidemic mice (Con), Lysimachiae Herba water extract administered mice (LWE), Lysimachiae Herba methanol extract administered mice (LME). Thereafter the changes in body weight, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, AST, ALT, fasting blood glucose in serum were measured. In addition histopathological changes in liver tissue was also observed. Results : Body weight, AST and ALT were not affected by the administration of water or methanol extracts of Lysimachiae Herba. However, methanol extracts of Lysimachiae Herba down regulated the total cholesterol and triglyceride in high fat diet - induced hyperlipidemic mice. Conclusions : In this study, results of total cholesterol and triglyceride showed significant effect in LME compared with LWE, but other results didn&#x2019;t. Therefore, it is necessary to have more study of Lysimachiae Herba to apply hyperlipidemia.

The rationality of the hypolipidemic effect of alismatis rhizoma decoction, a classical chinese medicine formula in high-fat diet-induced hyperlipidemic mice.

Alismatis Rhizoma Decoction (ARD) is a classical Traditional Chinese Medicine (TCM) formula for treatment of vertigo with its long history of successful clinical effect. Since vertigo is a symptom of hyperlipidemia, this study aimed at evaluating the hypolipidemic effect of ARD in hyperlipidemic mice induced by high fat diet (HFD) and investigated the rationality of formula combination of Alismatis Rhizoma (AR) and Atractylodis Macrocephalae Rhizoma (AMR). Compared with control group, hyperlipidemic mice in AR and ARD groups displayed a reduction of the following parameters: body weight, liver and serum total cholesterol, triglyceride concentration, liver and spleen coefficients, activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT); whereas the serum HDL-cholesterol levels were significantly elevated in both AR and ARD groups. AR and ARD treatments significantly down regulated the expressions of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoA reductase) and sterol regulatory element binding factor-2 (SREBF-2). These findings clearly provided evidences that the suppression on biosynthesis of cholesterol in liver may in part contribute to the hypolipidemic effects of ARD and AR. Since no significantly hypolipidemic effect of AMR was observed, the more prominent effect of ARD than that of AR indicated synergistic effects of AR and AMR, and confirmed the rationality of ARD formula.