Targeted changes in blood lipids improves fibrosis in renal allografts.

BACKGROUND: Chronic interstitial fibrosis is the primary barrier against the long-term survival of transplanted kidneys. Extending the lifespan of allografts is vital for ensuring the long-term health of patients undergoing kidney transplants. However, few targets and their clinical applications have been identified. Moreover, whether dyslipidemia facilitates fibrosis in renal allograft remains unclear. METHODS: Blood samples were collected from patients who underwent kidney transplantation. Correlation analyses were conducted between the Banff score and body mass index, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. A rat model of renal transplantation was treated with the lipid-lowering drug, fenofibrate, and kidney fibrosis levels were determined by histochemical staining. Targeted metabolomic detection was conducted in blood samples from patients who underwent kidney transplantation and were divided into fibrotic and non-fibrotic groups. Rats undergoing renal transplantation were fed either an n-3 or n-6 polyunsaturated fatty acid (PUFA)-enriched diet. Immunohistochemical and Masson's trichrome staining were used to determine the degree of fibrosis. RESULTS: Hyperlipidemia was associated with fibrosis development. Treatment with fenofibrate contributed to improve fibrosis in a rat model of renal transplantation. Moreover, n-3 PUFAs from fibrotic group showed significant downregulation compared to patients without fibrotic renal allografts, and n-3 PUFAs-enriched diet contributed to delayed fibrosis in a rat model of renal transplantation. CONCLUSIONS: This study suggests that hyperlipidemia facilitates fibrosis of renal allografts. Importantly, a new therapeutic approach was provided that may delay chronic interstitial fibrosis in transplanted kidneys by augmenting the n-3 PUFA content in the diet.

Zexie Tang targeting FKBP38/mTOR/SREBPs pathway improves hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Zexie Tang (ZXT), only two consists with Alismatis Rhizoma (AR) and Atractylodes macrocephala Rhizoma (AM), a classical Chinese medicine formula from Synopsis of the Golden Chamber with a history of 2000 years. Clinical observation in recent years has found that ZXT has excellent lipid-lowering effect. AIM OF THE STUDY: To explore the potential mechanism of ZXT ameliorates hyperlipidemia based on FKBP38/mTOR/SREBPs pathway. MATERIALS AND METHODS: WD-induced hyperlipidemia mice and oleic acid induced cell lipid accumulation model were used to investigate pharmacodynamic. The effect of ZXT on the transcriptional activity of SREBPs was detected by reporter gene assay. Proteins and downstream genes of mTOR/SREBPs pathway were detected in vivo and in vitro. Combined with network pharmacology and HPLC-Q-TOF/MS, the active ingredients were screened and identified. The interaction between active compounds of ZXT and FKBP38 protein were analyzed by docking analysis. RESULTS: ZXT decreased TC, TG and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo. ZXT also reduced TC, TG and lipid accumulation in cells line, and inhibited SREBPs luciferase activity, protein and its target genes expression such as FASN, HMGCR, etc. Meanwhile, ZXT inhibited protein expression levels of p-mTOR, p-S6K, etc in vitro and in vivo. Combined with network pharmacology and HPLC-Q-TOF/MS, 16 active ingredients were screened and identified. Docking results showed that active compounds of ZXT binding to FKBP38 and formed hydrogen bond. CONCLUSION: Our findings highlighted that ZXT ameliorates hyperlipidemia, in which FKBP/mTOR/SREBPs pathway might be the potential regulatory mechanism.

Polygonum cuspidatum Extract Exerts Antihyperlipidemic Effects by Regulation of PI3K/AKT/FOXO3 Signaling Pathway.

Polygonum cuspidatum (PC) has been reported to exert a potent antihyperlipidemic effect. However, its mechanisms of action and active ingredients remain elusive and require further research. In this study, we first conducted in vivo experiments to validate that Polygonum cuspidatum extract (PCE) could ameliorate the blood lipid level in hyperlipidemia model rats. Then, ultrahigh performance liquid chromatography coupled with Q-Exactive MS/MS (UPLC-QE-MS/MS) was applied to verify its 12 main active ingredients. The pharmacophore matching model was employed to predict the target point of the active ingredient, and 27 overlapping genes were identified via database and literature mining. String online database and Cytoscape software were utilized to construct a Protein-Protein Interaction (PPI) network, followed by function annotation analysis and pathway enrichment analysis. The results showed that the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors were significantly enriched. Furthermore, in vitro experiments were performed to determine the lipid content and oxidative stress (OS) indicators in OA-induced HepG2 cells, and immunofluorescence and western blotting analysis were carried out to analyze the effects of PCE on related proteins. Our experimental results show that the mechanism of antihyperlipidemic action of PCE is related to the activation of the PI3K/AKT signaling pathway and its downstream FOXO3/ERα factors, and polydatin and resveratrol are the main active ingredients in PCE that exert antihyperlipidemic effects.

Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD-Induced Insulin Resistance by Modulating IRS-1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways.

Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.

Design, synthesis, and biological evaluation of novel tetrahydroprotoberberine derivatives to reduce SREBPs expression for the treatment of hyperlipidemia.

Statins play an important role in the treatment of hyperlipidemia, but drug resistance and adverse effects greatly limits their application. To discover new lipid-lowering drugs, three different series of tetrahydroprotoberberine derivatives (THPBs) were designed and synthesized. These compounds were first tested for their effects on viability of HepG2 cells and 21 compounds with the percent of cell viability over 90% were further screened to evaluate their ability to reduce total cholesterol (TC) and triglyceride (TG) levels. Among these derivatives, two compounds displayed significant down-regulation both intracellular of TC and TG content, especially compound 49 exhibited the greatest efficacy. Mechanistically, compound 49 promoted proteasomal degradation of SREBPs. Importantly, compound 49 displayed superior bioavailability (F = 65.1%) and obvious efficacy in the treatment of high fat diet induced obesity in vivo. Therefore, compound 49 is a promising candidate to develop new treatment of hyperlipidemia.

Thymoquinone Protects against Hyperlipidemia-Induced Cardiac Damage in Low-Density Lipoprotein Receptor-Deficient (LDL-R-/-) Mice via Its Anti-inflammatory and Antipyroptotic Effects.

Hyperlipidemia is a risk factor for cardiac damage and cardiovascular disease. Increasing evidence has shown that dyslipidemia-related cardiac damage is associated with lipid accumulation, oxidative stress, and inflammation. Thymoquinone (TQ) is the major constituent of Nigella sativa, commonly known as black seed or black cumin, and is globally used in folk (herbal) medicine for treating and preventing a number of diseases and conditions. Several studies have shown that TQ can protect against cardiac damage. This study is aimed at investigating the possible protective effects of TQ on hyperlipidemia-induced cardiac damage in low-density lipoprotein receptor-deficient (LDL-R-/-) mice. Eight-week-old male LDL-R-/- mice were randomly divided into normal diet (ND), high-fat diet (HFD), and HFD and TQ (HFD+TQ) groups and were fed the different diets for eight weeks. Blood samples were obtained from the inferior vena cava in serum tubes and stored at -80°C until use. Some cardiac tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the cardiac tissues was snap-frozen in liquid nitrogen for mRNA preparation or immunoblotting. The levels of metabolism-related factors, such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP), were decreased in the HFD+TQ group compared with those in the HFD group. Periodic acid-Schiff staining demonstrated that lipid deposition was lower in the HFD+TQ group than in the HFD group. The expression of pyroptosis indicators (NOD-like receptor 3 (NLRP3), interleukin- (IL-) 1ß, IL-18, and caspase-1), proinflammatory factors (IL-6 and tumor necrosis factor alpha (TNF-α)), and macrophage markers (cluster of differentiation (CD) 68) was significantly downregulated in the HFD+TQ group compared with that in the HFD group. Our results indicate that TQ may serve as a potential therapeutic agent for hyperlipidemia-induced cardiac damage.

Nanoemulsification of Rice Bran Wax Policosanol Enhances Its Cardio-protective Effects via Modulation of Hepatic Peroxisome Proliferator-activated Receptor gamma in Hyperlipidemic Rats.

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects including lipid-lowering that have been extensively studied. However, its bioavailability is low. To investigate the effect of nanoemulsified rice bran wax policosanol (NPOL) on plasma homocysteine, heart and liver histology in hyperlipidemic rats, high-fat diet containing 2.5% cholesterol was used to induce hyperlipidemia in Sprague Dawley rats. The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol (POL) in comparison with normal diet (ND), high-cholesterol diet (HCD) and simvastatin-treated rats. Plasma homocysteine, heart and liver histology, and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) were evaluated. The NPOL group, similar to the simvastatin group, showed reduced plasma homocysteine, preserved heart and liver histology, and down-regulated hepatic PPARG mRNA in comparison to the control group, and was better than the POL group. The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background of increased assimilation of rice bran wax policosanol.

Mechanistic study of attenuation of monosodium glutamate mixed high lipid diet induced systemic damage in rats by Coccinia grandis.

In the context of failure of treatment for non alcoholic fatty liver disease (NAFLD)-mediated systemic damages, recognition of novel and successful characteristic drug to combat these anomalous situations is earnestly required. The present study is aimed to evaluate protective value of ethanol extract of Coccinia grandis leaves (EECGL), naturally occurring medicinal plant, on NAFLD-mediated systemic damage induced by high lipid diet along with monosodium glutamate (HM)-fed rats. Our study uncovered that EECGL significantly ameliorates HM-induced hyperlipidemia, increased lipogenesis and metabolic disturbances (via up regulation of PPAR-α and PPAR-γ), oxidative stress (via reducing the generation of reactive oxygen species and regulating the redox-homeostasis) and inflammatory response (via regulating the pro-inflammatory and anti-inflammatory factors with concomitant down regulation of NF-kB, iNOS, TNF-α and up regulation of eNOS). Furthermore, EECGL significantly inhibited HM-induced increased population of cells in sub G0/G1 phase, decreased Bcl2 expression and thereby loss of mitochondrial membrane potential with over expression of Bax, p53, p21, activation of caspase 3 and 9 indicated the apoptosis and suppression of cell survival. It is perhaps the first comprehensive study with a mechanistic approach which provides a strong unique strategy for the management of HM-induced systemic damage with effective dose of EECGL.

Successful treatment of a patient with mitochondrial myopathy with alirocumab.

A 48-year-old man presented to our lipid clinic with statin intolerance and elevated serum creatine kinase levels, being affected by mitochondrial myopathy because of heteroplasmic mitochondrial DNA missense mutation in MTCO1 gene (m.7671T>A). He had just been treated with a coronary artery bypass 4 years before because of acute coronary syndrome, and he had consistently high levels of both low-density lipoprotein cholesterol and triglycerides. Dyslipidemia was successfully treated using 75 mg of alirocumab subcutaneously every 2 weeks, 10 mg of ezetimibe daily, 2 g of marine omega-3 fatty acids daily, and 145 mg of micronized fenofibrate every 2 days. Although muscle weakness persisted, myalgia did not reoccur and serum creatine kinase levels remained almost stable over the time.

Huang-Qi San ameliorates hyperlipidemia with obesity rats via activating brown adipocytes and converting white adipocytes into brown-like adipocytes.

BACKGROUND: Brown adipose tissue (BAT) activation is a promising therapeutic target to treat hyperlipidemia with obesity. Huang-Qi San (HQS), an traditional Chinese medicine, can ameliorate hyperlipidemia with obesity, but its mechanism of action (MOA) is not understood. PURPOSE: To articulate the MOA for HQS with animal models. METHODS: The main chemical constituents of HQS were identified by high-performance liquid chromatography (HPLC) based assay. Hyperlipidemia with obesity rat models induced by high-fat diet were employed in the study. The levels of the fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were measured to evaluate the ability of HQS to ameliorate hyperlipidemia with obesity. Pathological analyses of organs were conducted with Oil Red O staining, hematoxylin-eosin (H&E) staining and transmission electron microscopy. The expression of mRNAs related to thermogenic genes, fatty acid oxidation-related genes and mitochondria biogenic genes were examined by quantitative real-time PCR. The protein expressions of uncoupling protein 1 (UCP1) were investigated by immunohistochemistry and western blot. Simultaneously, the protein expression of PR domain containing 16 (PRDM16), ATP synthase F1 subunit alpha (ATP5A) was detected by western blot. RESULTS: HQS ameliorates metabolic disorder, lipid ectopic deposition, obesity and maintained glucose homeostasis in hyperlipidemia with obesity rats. HQS can significantly increase the number of mitochondria and reduced the size of the intracellular lipid droplets in BAT, and increase the expression of BAT activation-related genes (UCP1, PGC1α, PGC1ß, Prdm16, CD137, TBX1, CPT1a, PPARα, Tfam, NRF1 and NRF2) in vivo. Furthermore, UCP1, PRDM16 and ATP5A proteins of BAT were increased. CONCLUSION: HQS can activate BAT and browning of S-WAT (subcutaneous white adipose tissue) through activating the PRDM16/PGC1α/UCP1 pathway, augmenting mitochondrial biogenesis and fatty acid oxidation to increase thermogenesis and energy expenditure, resulting in a significant amelioration of hyperlipidemia with obesity. Therefore, HQS is an effective therapeutic medicine for the treatment of hyperlipidemia with obesity.

Chronopharmacology of simvastatin on hyperlipidaemia in high-fat diet-fed obese mice.

The chronopharmacology refers to the utilization of physiological circadian rhythms to optimize the administration time of drugs, thus increasing their efficacy and safety, or reducing adverse effects. Simvastatin is one of the most widely prescribed drugs for the treatment of hypercholesterolaemia, hyperlipidemia and coronary artery disease. There are conflicting statements regarding the timing of simvastatin administration, and convincing experimental evidence remains unavailable. Thus, we aimed to examine whether different administration times would influence the efficacy of simvastatin. High-fat diet-fed mice were treated with simvastatin at zeitgeber time 1 (ZT1) or ZT13, respectively, for nine weeks. Simvastatin showed robust anti-hypercholesterolaemia and anti-hyperlipidemia effects on these obese mice, regardless of administration time. However, simvastatin administrated at ZT13, compared to ZT1, was more functional for decreasing serum levels of total cholesterol, triglycerides, non-esterified free fatty acids and LDL cholesterol, as well as improving liver pathological characteristics. In terms of possible mechanisms, we found that simvastatin did not alter the expression of hepatic circadian clock gene in vivo, although it failed to change the period, phase and amplitude of oscillation patterns in Per2::Luc U2OS and Bmal1::Luc U2OS cells in vitro. In contrast, simvastatin regulated the expression of Hmgcr, Mdr1 and Slco2b1 in a circadian manner, which potentially contributed to the chronopharmacological function of the drug. Taken together, we provide solid evidence to suggest that different administration times affect the lipid-lowering effects of simvastatin.

Ganoderma lucidum spore ethanol extract attenuates atherosclerosis by regulating lipid metabolism via upregulation of liver X receptor alpha.

CONTEXT: Ganoderma lucidum (Leyss.ex Fr.) Karst (Ganodermataceae) is a fungus that has been used in traditional Chinese medicine. OBJECTIVE: This is the first investigation of the lipid-lowering and anti-atherosclerotic effects of Ganoderma lucidum spore ethanol extract (EEG) in hyperlipidemic rabbits. MATERIALS AND METHODS: Fifty-four Japanese rabbits were randomly divided into six groups (n = 9): control, model, atorvastatin and three EEG groups (6, 24 and 96 mg/kg/day, p.o.). Control group was administered a normal diet and other groups were administered a high-fat diet to induce hyperlipidaemia and atherosclerosis for 14 weeks. During this time, lipid profiles were recorded; lipid testing and histopathological examination of aorta and liver were conducted. LXRα and its downstream genes expression in the liver and small intestine were examined. The effect of EEG on macrophage cholesterol efflux and ABCA1/G1 expression was observed under silenced LXRα expression. RESULTS: EEG reduced serum cholesterol (20.33 ± 3.62 mmol/L vs 34.56 ± 8.27 mmol/L for the model group) and LDL-C, reduced the area of arterial plaques (24.8 ± 10% vs 53.9 ± 15.2% for the model group) and Intima/Medium thickness ratio, increased faecal bile acid content, upregulated LXRα, CYP7A1, ABCA1/G1, ABCG5/G8 expression in the liver, small intestine and macrophages. After silencing LXRα in macrophages, the ability of EEG to promote cholesterol efflux was inhibited. DISCUSSION AND CONCLUSION: EEG exert lipid-lowering and anti-atherosclerotic effects via upregulating expression of LXRα and downstream genes associated with reverse cholesterol transport and metabolism. However, whether PPARα/γ are involved in the up-regulation of LXR expression by EEG remains to be elucidated.

Sacha inchi oil alleviates gut microbiota dysbiosis and improves hepatic lipid dysmetabolism in high-fat diet-fed rats.

Dietary ω-3 polyunsaturated fatty acids (PUFAs) are beneficial for humans against the development of hyperlipidaemia, but the underlying mechanisms are still poorly understood. Here, we demonstrated that oral consumption of sacha inchi oil, which is rich in α-linolenic acid, alleviated dyslipidemia, hepatic steatosis and inflammatory infiltration in high-fat diet (HFD)-fed rats. Sacha inchi oil administration reversed gut microbiota dysbiosis and altered the gut microbiota metabolome and in particular prevented bile acid dysmetabolism caused by a HFD. Sacha inchi oil intake ameliorated hepatic lipid dysmetabolism in HFD-fed rats, via potentiating the biosynthesis and reuptake of bile acids, reducing the de novo lipogenesis, promoting fatty acid beta-oxidation, and alleviating the dysregulation of glycerolipid, glycerophospholipid, and sphingolipid metabolisms. The results showed that dietary sacha inchi oil can alleviate gut microbiota dysbiosis and reduce lipid dysmetabolism in HFD rats, and provide novel insights into the molecular mechanisms by which plant-derived ω-3 PUFAs prevent the development of hyperlipidaemia.

Apigenin, flavonoid component isolated from Gentiana veitchiorum flower suppresses the oxidative stress through LDLR-LCAT signaling pathway.

Flower of Gentiana veitchiorum has traditionally been used as an herbal medicine in Tibet for treatment of variola, respiratory infection, and pneumonia. However, the effective components contained in flower are not identified yet, and the underlying mechanisms for anti-inflammatory, antibacterial, and antioxidative activities remain to be elucidated. Here, we first extracted the flavonoid mixture from G. veitchiorum flower. The mixture was then further isolated and the within compounds was identified through the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results showed that apigenin (4',5,7-trihydroxyflavone) was the most abundant flavonoid in G. veitchiorum flower. We next examined the antioxidative activity of the extracted apigenin using the ferric reducing/antioxidant power (FRAP), the 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assays and found that a positive correlation between apigenin concentration and reactive oxygen species (ROS) scavenging rate. The biochemical assays further revealed that the levels of total cholesterol (TC), triglyceride (TG), and malondialdehyde (MDA) were reduced, while the activity of superoxide dismutase (SOD) was increased after apigenin treatment in hyperlipidemic rats. Moreover, we performed histopathological investigations and found that the lipidic deposition patterns were recovered and the amount of lipid vacuoles was significantly reduced in apigenin-treated hyperlipidemic rat liver. Western blotting assay showed that the expression of low-density lipoprotein receptor (LDLR) and lecithin-cholesterol acyltransferase (LCAT) were up-regulated in the apigenin-treated samples. Overall, our results demonstrated that the apigenin isolated from G. veitchiorum flower exhibited radical scavenging activities, and reversed the high fat diet-induced oxidative damage in rats. Its antioxidative activities are probably achieved via LDLR-LCAT signaling pathway.

1H-NMR Metabolomics Analysis of the Effect of Rubusoside on Serum Metabolites of Golden Hamsters on a High-Fat Diet.

Rubusoside is a natural sweetener and the active component of Rubus suavissimus. The preventive and therapeutic effect of rubusoside on high-fat diet-induced (HFD) serum metabolite changes in golden hamsters was analyzed by 1H-NMR metabolomics to explore the underlying mechanism of lipid metabolism regulation. 1H-NMR serum metabolomics analyses revealed a disturbed amino acid-, sugar-, fat-, and energy metabolism in HFD animals. Animals supplemented with rubusoside can partly reverse the metabolism disorders induced by high-fat diet and exerted good anti-hypertriglyceridemia effect by intervening in some major metabolic pathways, involving amino acid metabolism, synthesis of ketone bodies, as well as choline and 4-hydroxyphenylacetate metabolism. This study indicates that rubusoside can interfere with and normalize high-fat diet-induced metabolic changes in serum and could provide a theoretical basis to establish rubusoside as a potentially therapeutic tool able to revert or prevent lipid metabolism disorders.

The Underlying Mechanisms of Curcumin Inhibition of Hyperglycemia and Hyperlipidemia in Rats Fed a High-Fat Diet Combined With STZ Treatment.

Curcumin is the main secondary metabolite of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect of curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF + STZ group), and a high-fat diet combined with curcumin and STZ group (HF + Cur + STZ group). Compared with the HF + STZ group, the HF + Cur + STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST), and aspartate transaminase (ALT) levels, as well as liver coefficients. In the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

Ulmus macrocarpa Hance modulates lipid metabolism in hyperlipidemia via activation of AMPK pathway.

Ulmus macrocarpa Hance as an oriental medicinal plant has shown enormous potential for the treatment of several metabolic disorders in Korea. Hyperlipidemia, which is characterized by the excess accumulation of lipid contents in the bloodstream, may lead to several cardiovascular diseases. Therefore, in this study, anti-hyperlipidemic potential of U. macrocarpa water extract (UME) was examined in vitro and in vivo using HepG2 cells and experimental rats, respectively. The hyperlipidemia in experimental rats was induced by the high-cholesterol diet (HCD) followed by oral administration of various concentrations (25, 50 and 100 mg/kg) of UME for 6 weeks. As a result, the UME significantly improved the biochemical parameters such as increased the level of triglyceride, total cholesterol, and low-density lipoprotein cholesterol as well as reduced the high-density lipoprotein cholesterol in the HCD-fed rats. In addition, UME also prevented lipid accumulation through regulating AMPK activity and lipid metabolism proteins (ACC, SREBP1 and HMGCR) in the HCD-fed rats as compared to the controls. Moreover, similar pattern of gene expression levels was confirmed in oleic acid (OA)-treated HepG2 cells. Taken together, our results indicate that UME prevents hyperlipidemia via activating the AMPK pathway and regulates lipid metabolism. Thus, based on the above findings, it is estimated that UME could be a potential therapeutic agent for preventing the hyperlipidemia.

The effect of bergamot polyphenolic fraction on lipid transfer protein system and vascular oxidative stress in a rat model of hyperlipemia.

BACKGROUND: Experimental and epidemiological studies show that bergamot polyphenolic fraction (BPF) ameliorates the serum lipemic profile, normalizes blood pressure and improves non alcoholic fatty liver disease in patients suffering from metabolic syndrome. Despite this evidence, the molecular mechanisms responsible for these beneficial effects remain unclear. The aim of our study is to clarify the effects of BPF on the lipoprotein assembly and to identify oxidative stress biomarkers correlating hyperlipidaemia and BPF-induced metabolic changes. METHODS: Male Wistar rats (180-200 g) were randomly assigned to receive a standard diet, a hypercholesterolemic diet or a hypercholesterolemic diet+BPF (20 mg/Kg/rat daily, gavage), respectively, for 90 days. Total cholesterol (tChol), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and fasting plasma glucose were evaluated at the baseline as well as at the end of the treatment. To assess the effect of BPF on the Lipid Transfer Protein System, detection of ACAT, LCAT, CETP, PON1, Apo A1 and Apo B have also been carried out. Finally, the lipid peroxidation biomarker (TBARS) and oxyLDL were also measured. RESULTS: BPF prevented tChol, LDL-C, TG and fasting plasma glucose enhancement and improved HDL-C. Treatment of hyperlipæmic rats with BPF significantly restored altered the serum concentration of lipemic biomarkers and the activity of ACAT, LCAT, CETP and PON1, an effect accompanied by the concomitant normalization of Apo A1 and APO B levels. In addition, TBARS levels were reduced significantly by the treatment with BPF. CONCLUSIONS: BPF prevents diet-induced alteration of the lipid profile in rats, counteracting oxidative stress and improving the dysregulation of the Lipid Transfer Protein System. These data add new insights into the molecular mechanisms underlying the beneficial role of BPF in the therapy of hyperlipidaemia, thus suggesting a novel approach in the prevention of cardiovascular disease.

Antioxidant Effects of Baoyuan Decoction on Dysfunctional Erythrocytes in High-Fat Diet-Induced Hyperlipidemic ApoE-/- Mice.

Baoyuan decoction (BYD), a traditional representative formula, has a long usage history in the treatment of cardiovascular diseases. Since the hyperlipidemia-induced dysfunction of erythrocyte is one of the most important causes of cardiovascular diseases, the improving effects of BYD against high-fat diet (HFD) induced the physiological and physical function of the erythrocytic injury and the potential mechanisms were deeply researched in this study. After 6 weeks of drug treatment, all doses of BYD had significantly decreased the lipid peroxidation in plasma of HFD-induced ApoE-/- mice, even if it had not improved the lipid levels. Then, the erythrocyte-related experimental results showed that BYD had reduced erythrocyte osmotic fragility, stabilized erythrocyte membrane skeleton protein 4.2, and reformed the erythrocyte morphological changes by decreasing erythrocyte membrane lipid peroxidation levels. This study demonstrated that BYD may ameliorate the physiological and physical function of erythrocyte in hyperlipidemic mice through the antioxidant effect on erythrocyte membranes.

Efficacy of a Methanolic Extract of Adansonia digitata Leaf in Alleviating Hyperglycemia, Hyperlipidemia, and Oxidative Stress of Diabetic Rats.

Traditionally, in many countries, various parts of the Adansonia digitata (A. digitata) tree have been used in the treatment of many clinical ailments including diarrhea and dysentery. The phytochemical screening has indicated that the leaf extract of A. digitata contains flavonoids, saponins, mucilage, steroids, and alkaloids. Thus, this paper aims to evaluate the hyperglycaemic and hypolipidaemic effects of methanolic extract of A. digitata leaves (200 mg/kg and 400 mg/kg) in diabetic rats. The extract was administered orally for six weeks in the streptozotocin (STZ)-induced diabetic rats. The treatment with the extract caused a significant reduction in the blood glucose, glycosylated hemoglobin, cholesterol, triglycerides, low-density lipoprotein (LDL), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) levels by 46.7%, 46.15%, 48.91%, 43%, 60%, 66%, 45.45%, and 30.4%, respectively, as compared to the diabetic group after the sixth week of treatment. The leaf extract also mitigated the decline of high-density lipoprotein (HDL) level, RBCs count, hemoglobin level, packed cell volume (PCV %), and erythropoietin concentration in diabetic rats by 31%, 33.25%, 24.72%, 51.42%, and 220.68% with respect to the diabetic group. Also, the extract maintained the level of antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), and reduced glutathione (GSH) in the diabetic rats. It also reduced the elevation in the white blood corpuscles (WBC) count in the STZ-induced diabetic rats. Our study, therefore, indicates that methanolic extract of A. digitata leaf exerts strong antidiabetic and hypolipidaemic properties in a dose-dependent manner by improving the hematological properties and redox parameters in the experimental diabetic rats.