Diet-induced Hyperlipidemic Mice Research Articles

Alleviation of High-Fat Diet-Induced Hyperlipidemia in Mice by Stachys sieboldii Miq. Huangjiu via the Modulation of Gut Microbiota Composition and Metabolic Function.

Hyperlipidemia is a chronic disease that is difficult to cure, and long-term pharmacotherapy may have negative consequences. Dietary therapy is a very promising strategy, and Chinese rice wine (Huangjiu) will play an important role because of its many biologically active components. In this work, the alleviating effect of Stachys sieboldii Miq. Huangjiu (CSCHJ) on high-fat diet-induced hyperlipidemia in mice was investigated, which is brewed from the wheat Qu with the addition of Stachys sieboldii Miq. and contains 15.54 g/L of polysaccharides. The experimental results showed that CSCHJ inhibited appetite, reduced body weight and blood sugar levels, and downregulated the serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) while concurrently upregulating high-density lipoprotein cholesterol (HDL-C) in the high-fat diet-induced hyperlipidemia mice. At the same time, it was discovered that alcohol worsens hyperlipidemia symptoms and related physiological markers, implying that CSCHJ polysaccharides may play a role in hyperlipidemia treatment. Through the assessment of organ indices, liver and kidney function, and tissue staining, CSCHJ demonstrated efficacy in repairing liver, kidney, and colon mucosal damage in hyperlipidemic mice. Furthermore, 16S rDNA sequencing and gas chromatography studies revealed that CSCHJ effectively restored the intestinal microbial structure and enhanced the quantity of fecal short-chain fatty acids (SCFAs) in hyperlipidemic mice. Therefore, the alleviating effect of CSCHJ on hyperlipidemia in mice may be attributed to its regulation of energy metabolism by repairing liver, kidney, and colon mucosal damage and restoring the gut microbiota structure, among other mechanisms. Overall, our findings provide evidence that CSCHJ contains active ingredients capable of alleviating hyperlipidemia, thereby laying a theoretical foundation for the extraction of bioactive substances from Huangjiu for future medical or dietary use.

FBXO28 reduces high-fat diet-induced hyperlipidemia in mice by alleviating abnormal lipid metabolism and inflammatory responses.

Hyperlipidemia is a lipid metabolism disorder with increasing incidence and prevalence worldwide. Abnormal lipid metabolism and inflammation are two significant characteristics of hyperlipidemia. The purpose of this study was to explore the role and mechanism of F-box only protein 28 (FBXO28) in hyperlipidemia. Mice were fed with high-fat diet (HFD) to elicit obesity, and 3T3-L1 preadipocytes were stimulated with MDI cocktail (IBMX, DEX and insulin) to evoke differentiation. In vivo and in vitro role of FBXO28 in hyperlipidemia was investigated by hematoxylin-eosin and oil Red O staining, the lipid biochemistry measurement, enzyme-linked immunosorbent assay, reverse transcription quantitative polymerase chain reaction and western blotting assays. The mechanism of FBXO28 explored by co-immunoprecipitation, immunofluorescence, ubiquitination and cycloheximide assays. Low expression of FBXO28 was found in hyperlipidemia in silico, in vivo and in vitro. Upregulation of FBXO28 declined the body weight, fat accumulation, and serum lipid content in HFD-fed mice. Abnormal lipid accumulation, and the level of liposynthetic genes and beta-oxidation related genes were improved by overexpression of FBXO28 both in HFD-elicited mice and MDI-treated 3T3-L1 preadipocytes. Besides, overexpression of FBXO28 declined HFD-induced the level of proinflammatory factors and F4/80. Mechanically, FBXO28 directly bound RAB27A and promoted its ubiquitinated degradation. Thus, upregulation of RAB27A inverted the improved role of FBXO28 in abnormal lipid metabolism and inflammation in vivo and in vitro. FBXO28 ameliorated abnormal lipid metabolism and inflammation through the ubiquitinated degradation of RAB27A, thereby attenuating HFD-induced hyperlipidemia. The results could promote the treatment of hyperlipidemia, and the relevant diseases.

Complexes of Soluble Dietary Fiber and Polyphenols from Lotus Root Regulate High-Fat Diet-Induced Hyperlipidemia in Mice.

In this paper, complexes of soluble dietary fiber (SDF) and polyphenols (PPs) isolated from lotus roots were prepared (SDF-PPs), as well as physical mixtures (SDF&PPs), which were given to high-fat-diet (HFD)-fed mice. The results demonstrated that SDF-PPs improve lipid levels and reverse liver injury in hyperlipidemic mice. Western blotting and real-time quantitative Polymerase Chain Reaction (RT-qPCR) results showed that SDF-PPs regulated liver lipids by increasing the phosphorylation of Adenine monophosphate activated protein kinase (AMPK), up-regulating the expression of Carnitine palmitoyltransferase1 (CPT1), and down-regulating the expression of Fatty acid synthase (FAS) and 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA), as well as the transcription factor sterol-regulatory element binding protein (SPEBP-1) and its downstream liposynthesis genes. Additionally, the intervention of SDF-PPs could modulate the composition of intestinal gut microbes, inducing an increase in Lachnospiraceae and a decrease in Desulfovibrionaceae and Prevotellaceae in high-fat-diet-fed mice. Thus, the research provides a theoretical basis for the application of lotus root active ingredients in functional foods and ingredients.

Highly crystalline cellulose microparticles from dealginated seaweed waste ameliorate high fat-sugar diet-induced hyperlipidemia in mice by modulating gut microbiota

The effects of seaweed cellulose (SC) on high fat-sugar diet (HFSD)-induced glucolipid metabolism disorders in mice and potential mechanisms were investigated. SC was isolated from dealginated residues of giant kelp (Macrocystis pyrifera), with a crystallinity index of 85.51 % and an average particle size of 678.2 nm. Administering SC to C57BL/6 mice at 250 or 500 mg/kg BW/day via intragastric gavage for six weeks apparently inhibited the development of HFSD-induced obesity, dyslipidemia, insulin resistance, oxidative stress and liver damage. Notably, SC intervention partially restored the structure and composition of the gut microbiota altered by the HFSD, substantially lowering the Firmicutes to Bacteroidetes ratio, and greatly increasing the relative abundance of Lactobacillus, Bifidobacterium, Oscillospira, Bacteroides and Akkermansia, which contributed to improved short-chain fatty acid (SCFA) production. Supplementing with a higher dose of SC led to more significant increases in total SCFA (67.57 %), acetate (64.56 %), propionate (73.52 %) and butyrate (66.23 %) concentrations in the rectal contents of HFSD-fed mice. The results indicated that highly crystalline SC microparticles could modulate gut microbiota dysbiosis and ameliorate HFSD-induced obesity and related metabolic syndrome in mice. Furthermore, particle size might have crucial impact on the prebiotic effects of cellulose as insoluble dietary fiber.

Tetrahydroberberine alleviates high-fat diet-induced hyperlipidemia in mice via augmenting lipoprotein assembly-induced clearance of low-density lipoprotein and intermediate-density lipoprotein

The promotion of excess low-density lipoprotein (LDL) clearance stands as an effective clinical approach for treating hyperlipidemia. Tetrahydroberberine, a metabolite of berberine, exhibits superior bioavailability compared to berberine and demonstrates a pronounced hypolipidemic effect. Despite these characteristics, the impact of tetrahydroberberine on improving excessive LDL clearance in hyperlipidemia has remained unexplored. Thus, this study investigates the potential effects of tetrahydroberberine on high-fat diet-induced hyperlipidemia in mice. The findings reveal that tetrahydroberberine exerts a more potent lipid-lowering effect than berberine, particularly concerning LDL-cholesterol in hyperlipidemic mice. Notably, tetrahydroberberine significantly reduces serum levels of upstream lipoproteins, including intermediate-density lipoprotein (IDL) and very low-density lipoprotein, by promoting their conversion to LDL. This reduction is further facilitated by the upregulation of hepatic LDL receptor expression induced by tetrahydroberberine. Intriguingly, tetrahydroberberine enhances the apolipoprotein E (ApoE)/apolipoprotein B100 (ApoB100) ratio, influencing lipoprotein assembly in the serum. This effect is achieved through the activation of the efflux of ApoE-containing cholesterol in the liver. The ApoE/ApoB100 ratio exhibits a robust negative correlation with serum levels of LDL and IDL, indicating its potential as a diagnostic indicator for hyperlipidemia. Moreover, tetrahydroberberine enhances hepatic lipid clearance without inducing lipid accumulation in the liver and alleviates existing liver lipid content. Importantly, no apparent hepatorenal toxicity is observed following tetrahydroberberine treatment for hyperlipidemia. In summary, tetrahydroberberine demonstrates a positive impact against hyperlipidemia by modulating lipoprotein assembly-induced clearance of LDL and IDL. The ApoE/ApoB100 ratio emerges as a promising diagnostic indicator for hyperlipidemia, showcasing the potential clinical significance of tetrahydroberberine in lipid management.

Carboxymethylated Lycium barbarum seed dreg dietary fiber alleviates high fat diet-induced hyperlipidemia in mice via intestinal regulation.

In this study, we investigated the ameliorative gut modulatory effect of carboxymethylated Lycium barbarum seed dreg insoluble dietary fiber (LBSDIDF) on hyperlipidemic mice. After seven weeks of insoluble dietary fiber (IDF) intervention, the results demonstrated that IDFs effectively inhibited body weight gain, with slimming and hypolipidemic effects, and improved liver histopathology by decreasing ALT, AST, TNF-α and IL-6, and increasing short-chain fatty acid (SCFA) levels in hyperlipidemic mice. With the increasing diversity and abundance of intestinal bacteria and decreasing ratio of Firmicutes to Bacteroidetes, intestinal flora facilitated cholesterol lowering effects in hyperlipidemic mice. Our research offers a novel concept for the use of LBSDIDF as a prebiotic to improve intestinal dysbiosis or as a preventive measure against obesity and dyslipidemia.

Loquat fruit peel extract regulates lipid metabolism and liver oxidative stress in mice: In vivo and in silico approaches.

In Moroccan traditional medicine, fresh or dried loquat (Eriobotrya japonica (Thunb.) Lindl.) fruit peels infused in water and taken for 45 days are used as natural remedies against hypercholesterolemia, hyperglycemia and cardiovascular diseases. This is the first experimental study approving the folk medicinal use of loquat fruit peels originated from eastern Morocco. The study aims to investigate the effect of loquat fruit peel extract on lipid metabolism and liver oxidative status in mice as well as to predict the possible mechanisms. The study was carried out using high fat/fructose diet-induced hyperlipidemic mice model treated with the loquat peel extract for 45 days at two doses (100 and 200mg/kg/day) in comparison to fenofibrate drug. The plasma, tissue, fecal and biliary lipids and blood glucose were analyzed using enzymatic methods. The liver oxidative status was evaluated and the polyphenol profiling was conducted using the HPLC-DAD method. Possible mechanisms involved in the observed pharmacological effects were predicted by in silico method. The extract at a dose of 200mg/kg possessed higher effect than at 100mg/kg. It significantly reduced plasma total cholesterol (TC), triglycerides (TG), LDL-cholesterol, atherogenic index, LDL-C/HDL-C ratio and plasma glucose (-36%, -45%, -45%, -82%, -87%, 58%, respectively), while the HDL-cholesterol was increased (+172%). Moreover, the extract reduced TC and TG in the liver and adipose tissue by increasing their excretion in bile and fecal matter. It prevented the liver oxidative stress and decreased body weight and organ relative mass. The extract appears to be nontoxic (LD50>5000mg/kg) and contains five polyphenols including ferulic acid (32.74±0.71mg/g), caffeic acid (21.48±0.32mg/g), 5-O-Caffeoylquinic acid (112.15±1.86mg/g), chlorogenic acid (42.05±0.92mg/g) and quercetin (32.69±0.68mg/g). These phenolics and/or their circulating metabolites presented differential interaction capacities with the potential enzymes and transcription factors implicated in lipid homeostasis such as HMG-CoA reductase, lipoprotein lipase, fatty acid synthase, Cyp7a1, ABCG, PPARs, RXR, FXR and RAR. Our findings justify the traditional use of loquat fruit peels and suggest that their aqueous extract could be used as substrate to produce phytotherapeutic drugs or dietary supplements to prevent hyperlipidemia, hyperglycemia and related cardiovascular diseases.

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.

Probiotic-fermented rice buckwheat alleviates high-fat diet-induced hyperlipidemia in mice by suppressing lipid accumulation and modulating gut microbiota

Hyperlipidemia is associated with lipid metabolic disorders, chronic inflammation, and intestinal dysbiosis. Previous studies have shown that the metabolic improvement of high-fat diet (HFD)-induced mice by buckwheat is correlated with gut microbiota; however, the anti-hyperlipidemia effects and potential mechanism of probiotics-fermented rice buckwheat (FRB) are not well understood. Here, we aimed to investigate the lipid-lowering and gut microbiota regulation of FRB in HFD-induced hyperlipidemic mice. We observed that probiotic fermentation markedly increased the contents of γ-aminobutyric acid, rutin, total polyphenols, and total flavonoids in rice buckwheat. FRB supplementation over eight weeks significantly reduced body weight gain and visceral obesity, as well as alleviating dyslipidemia in HFD-fed mice. Moreover, FRB treatment effectively ameliorated oxidative stress and chronic inflammation. We further demonstrated that FRB intervention significantly inhibited hepatic cholesterol synthesis and lipogenesis, and promoted lipolysis. More important, FRB treatment reversed HFD-induced gut dysbiosis by decreasing the ratio of Firmicutes to Bacteroidetes and increasing the abundance of SCFA-producing bacteria such as Bacteroides, Lactobacillus, and Blautia, along with increasing the total SCFAs contents. Overall, these results show that FRB is a beneficial nutraceutical for hyperlipidemia amelioration.

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.

Improved Oral Bioavailability and Hypolipidemic Effect of Syringic Acid via a Self-microemulsifying Drug Delivery System.

This study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the solubility, oral bioavailability, and hypolipidemic effects of syringic acid (SA), a bioactive and poorly-soluble polyphenol. Based on the response surface methodology-central composite design (RSM-CCD), an optimum formulation of SA-SMEDDS, consisting of ethyl oleate (oil, 12.30%), Cremophor-EL (surfactant, 66.25%), 1,2-propanediol (cosurfactant, 21.44%), and drug loading (50mg/g), was obtained. The droplets of SA-SMEDDS were nanosized (16.38 ± 0.12nm), spherically shaped, and homogeneously distributed (PDI = 0.058 ± 0.013) nanoparticles with high encapsulation efficiency (98.04 ± 1.39%) and stability. In vitro release study demonstrated a prolonged and controlled release of SA from SMEDDS. In vitro cell studies signified that SA-SMEDDS droplets substantially promoted cellular internalization. In comparison with the SA suspension, SA-SMEDDS showed significant prolonged Tmax, t1/2, and MRT after oral administration. Also, SA-SMEDDS exhibited a delayed in vivo elimination, increased bioavailability (2.1-fold), and enhanced liver accumulation. Furthermore, SA-SMEDDS demonstrated significant improvement in alleviating serum lipid profiles and hepatic steatosis in high-fat diet-induced hyperlipidemia in mice. Collectively, SMEDDS demonstrated potential as a nanosystem for the oral delivery of SA with enhanced bioavailability and hypolipidemic effects.

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.

Proteomic analysis of liver in diet-induced Hyperlipidemic mice under Fructus Rosa roxburghii action

Fructus Rosae Roxburghii (FRR) has been considered as edible and medicinal fruit possessing antiatherosclerotic effect, but the mechanism is still unclear. HLP is material basis for AS formation. Under FRR action, TC, TG, LDL, HDL and ASI in serum were regulated to control level. Differentially expressed proteins in liver were analyzed by using TMT labeling and LC-MS/MS for better understanding the effect and molecular mechanism of FRR on diet-induced hyperlipidemic mice. In total, 4460 proteins were quantified, of which 469 proteins showed dramatic changes between each group. According to molecular functions, 25 differentially co-expressed proteins were divided into five categories: substance metabolism, energy transformation and signal transduction, transcription and translation, immune defense. 15 key proteins involved lipids metabolism, which were identified as Cyp7a1, Cyp3a11, Tm7sf2, COAT2, CSAD, RBP3, Lpin1, Dhrs4, Aldh1b1, GK, Acot 4, TSC22D1, PGFS, EHs, GSTM1. This suggested that FRR could maintain metabolic homeostasis by regulating the metabolism of fatty acids, biosynthesis of BAs and steroids, and production of LPOs. 20 oxidative lipids further confirmed their importance regulating lipids metabolism. It's first time potential antiatherosclerotic mechanism of FRR regulating blood lipids was explored from protein level, which is of great significance to explore new drug targets for AS. SignificanceUnder the action of FRR juice, the blood lipids in mice were regulated to control level. By TMT proteomic analysis, the effect and molecular mechanism of FRR on diet-induced hyperlipidemic mice were further explored. 25 differentially co-expressed proteins obtained in three diet groups might cooperatively regulate the lipids metabolism and hepatic function of mice, thus maintaining the metabolism homeostasis. By lipidomics analysis, 20 oxidative lipids further confirmed the importance of ω-3 and ω-6 PUFAs in regulating the lipids metabolism. These findings provide an improved understanding for the regulation of FRR on the blood lipids and explores potential metabolic targets for AS prevention.

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 ofTrixis angustifoliaAqueous 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.

Anti-hyperlipidemic effects of Caralluma edulis (Asclepiadaceae) and Verbena officinalis (Verbenaceae) whole plants against high-fat diet-induced hyperlipidemia in mice

Purpose: To investigate the anti-hyperlipidemic effect of Caralluma edulis and Verbena officinalis.Methods: Phytochemical analysis of crude extracts of Caralluma edulis (Ce.Cr) and Verbena officinalis (Vo.Cr) were carried out. Hyperlipidemia was induced in mice with high-fat diet (HFD, 1.25 % w/w cholesterol, 0.5 % w/w cholic acid and 10 % v/w coconut oil). All the groups, except the saline-treated group, were fed on HFD for 4 weeks (lead-in period) to induce hyperlipidemia. Thereafter, the groups were treated with varying doses of the plant extract for 2 weeks (treatment period) as well as atorvastatin (10 mg/kg) reference standard. Body weight was measured fortnightly for all groups. Total cholesterol (TC), triglyceride (TGs) and low density lipoprotein (LDL) were assayed using Merck diagnostic kits. For histopathological analysis, liver slices were fixed in 10 % formalin and embedded in paraffin wax and was examined with the aid of hematoxylin and eosin staining (H &amp; E).Results: Caralluma edulis (Ce.Cr) contains saponins, alkaloids, tannins, phenol, glycosides, terpenoids and flavonoids while Verbena officinalis (Vo.Cr) tested positive for the presence of alkaloids, carbohydrates, flavonoids, saponins and tannins. HFD increased total cholesterol (TC), triglyceride (TGs), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) compared to regulator diet (p &lt; 0.001). Treatment of the animals with Ce.Cr and Vo.Cr dose-dependently (500 - 1000 mg/kg) reduced serum TC, TGs, LDL and VLDL (p &lt; 0.05, p &lt; 0.01, p &lt; 0.001, vs. HFD group) and raised high density lipoprotein (HDL) (p &lt; 0.01, vs. HFD group), similar to that observed with atorvastatin (10 mg/kg). The anti-hyperlipidemic effects of Ce.Cr and Vo.Cr were also confirmed via liver histopathology results, showing improved structure with no hepatocellular necrosis and fat accumulation.Conclusion: These results indicate that Caralluma edulis and Verbena officinalis exhibit antihyperlipidemic effect; thus, the plants have therapeutic potentials for the management of lipid disorders.Keywords: Caralluma edulis, Verbena officinalis, Anti-hyperlipidemia, Hepatocellular necrosis