Hyperlipidemic Model Research Articles

Atorvastatin prevents hearing impairment in the presence of hyperlipidemia

It is known that hyperlipidemia is a risk factor for sensorineural hearing loss. However, the biological mechanisms underlying hyperlipidemia and hearing impairment have not been completely elucidated in the cochlea. Based on our previous study of human subjects, elderly people taking drugs for hyperlipidemia showed better hearing than those not taking any medications. We hypothesized that drugs for hyperlipidemia, such as statins, may have the potential to prevent hearing impairment. The aim of this study was to investigate the correlation between hyperlipidemia and hearing impairment and the hearing preservation effect of atorvastatin using a hyperlipidemic mouse model with diet-induced obesity (DIO). Here, we demonstrate that DIO mice had a significant hearing impairment as well as increased levels of reactive oxygen species (ROS) and hair cell death due to reduced levels of pAKT and superoxide dismutase 2 (SOD2). However, these changes were significantly prevented by atorvastatin. Oxidative stress-induced intrinsic apoptosis was decreased by the high expression of Nrf2 and antioxidant genes, which improved mitochondrial function and ROS via activation of the PI3K-pAKT pathway by atorvastatin. Therefore, atorvastatin has the potential to prevent hearing impairment via redox balance in the presence of hyperlipidemia.

Glucose- lowering effect of Trametes orientalis polysaccharides in hyperglycemic and hyperlipidemic mice

To explore the glucose-lowering effect of the polysaccharide fractions of Trametes orientalis. The crude polysaccharides of T. orientalis were chromatographed on DEAE cellulose column using H2O and 0.5 mol/L NaCl solution as the eluent and DEAE-water and DEAE-salt with high polysaccharide contents were collected. The two fractions were separated using Sephadex G-100 gel column to obtain 4 polysaccharide fractions TOPW-1, TOPW-2, TOPS-1, and TOPS-2. The anti-oxidation activity of the polysaccharide fractions was investigated with ABTS method. The fractions TOPW-1 and TOPS-1 with consistent UV detection signals were collected and HPGPC was used to determine their relative molecular mass. The monosaccharide composition in homogeneous TOPW-1 was determined by acid hydrolysis combined with HPLC. The in vitro inhibitory activities of TOPW-1 and TOPS-1 against DPP4, adipocyte glucose intake and lipase activity were tested to preliminarily assess their glucose-lowering effect. In a mouse model of hyperglycemic and hyperlipidemic, the glucose-lowering effect of TOPS-1 (0.1, 0.2, and 0.4 g/kg) and its effect on blood lipid metabolism were investigated in comparison with Xiaoke pills (5 pills/kg) and Danshen tablets (0.5 g/kg). TOPW-1 was a homogeneous polysaccharide composed mainly of D-mannose, D-glucose, D-galactose, and D-fucose, with weak antioxidant and hypoglycemic effects. TOPS-1 was not a single polysaccharide and at the concentration of 500 μg/mL showed an high ABTS clearance rate (90.15%). In the mouse model of hyperglycemia and hyperlipidemia, treatment with TOPS-1 (0.2 g/kg) enhanced the activity of lipase and significantly reduced fasting glucose level and serum contents of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol without causing death in the mice. The glucose-lowering effects of TOPS-1 was not significant at the low (0.1 g/kg) or high (0.4 g/kg) dose, and a high dose tended to increase the mortality of the mice. T. orientalis polysaccharides have anti-oxidation, glucose-lowering and lipid-lowering effects in mice, and their glucose-lowering effect is probably medicated by reducing oxidative stress and ameliorating lipid metabolism disorder.

Characteristic chemical profile of Juhe Fang extract with lipid-lowering properties

The objective of this study was to verify the lipid-lowering effect of Juhe Fang extract (JHFE) and to determine its characteristic chemical profile in vitro and in vivo . A hyperlipidemia model was established by feeding mice a high-fat diet (HFD). After treatment for 30 days, serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured with an automatic biochemistry analyzer. The components from JHFE obtained from in vivo and in vitro experiments were investigated using an UPLC-Q Exactive-Orbitrap MS/MS. The TC, TG, and LDL-C in the serum significantly decreased and the HDL-C significantly increased after JHFE treatment. A total of 95 compounds from JHEF including 15 phenolic acids (PA), 4 phenylethanoid glycosides (PG), 24 flavonoids (F), 14 triterpenoids (T), 10 diterpenoid glycosides (D), 18 alkaloids (A) and 10 others (O) were identified. Trigonelline was discovered for the first time in a herbal medicine of Juhe Fang. Furthermore, 68 compounds were identified in vivo including 28 prototype compounds and 40 metabolites. The metabolic characteristics of these components were revealed including identification of new metabolites of 4-hydroxyphenyl ethyl-8-O-[α-L- arabinopyranosyl-(1 → 6)]-β-D-glucopyranoside (PEG) and lirinidine. A total of 43 components from JHFE were absorbed and/or metabolized. The contribution rate of each type of chemical component from JHFE to its lipid-lowering effect from high to low were A, F, PG, PA, D and T. The results of this study showed that JHFE demonstrated a significant lipid-lowering effect in a high-fat diet (HFD)-induced hyperlipidemia mouse model. Specific types of PA, PG, F, D, T and A formed the pharmaceutical architecture of the lipid-lowering effect of JHFE. This study should prove useful for clarifying the components responsible for the lipid-lowering effect of JHFE and provide a basis for precision quality control research.

Protective role of Convolvulus pluricaulis on lipid abnormalities in high-fat diet with low dose streptozotocin-induced experimental rat model

BackgroundThe methanolic extract of Convolvulus pluricaulis had earlier shown lipid lowering activity in Triton induced reversible hyperlipidemia model, but, the hypolipidemic activity in irreversible models and hypoglycaemic activity are not investigated so far. ObjectiveThis study was designed to validate the lipid and glucose-lowering actions of C. pluricaulis methanolic extract (CPME) by using ingredients from the Indian diet for induction of hyperlipidemia and diabetes on experimental rats. Materials and methodsExperimental animals were divided into four groups having six animals in each group (n = 6). Animals of Group I II, III and IV received - no treatment, 0.9% NaCl, Glipizide (GPZ) 5 mg/kg and CPME 400 mg/kg once daily for two weeks respectively. Animals of all groups except group I were fed a high fat-based Indian diet for 21 days followed by a single STZ (35 mg/kg) i.p. administration in model induction phase. Afterwards, animals were sacrificed, and the pancreas was dissected for histological changes, and blood was collected for measuring lipid parameters, FBS, insulin levels, and HOMA scores. ResultsCPME significantly ameliorate the lipid abnormalities in HFD-STZ-treated experimental model (p < 0.001) but fails to reverse the hyperglycaemia developed in diabetic rats with no protective effect on islet architecture (p > 0.05) as compared to experimental group while, GPZ showed protective effect on both lipid abnormalities and hyperglycemia by modulating the levels of lipid parameters and insulin respectively. ConclusionIn conclusion, the study confirm that CPME possesses significant hypolipidemic activity but fails to reverse the hyperglycaemia developed in diabetic rats.

Аtherosclerosis-like changes in the rabbit aortic wall induced by immunization with native high-density lipoproteins.

IntroductionA high level of total cholesterol or low‐density lipoprotein (LDL) cholesterol is considered the main cause of atherosclerosis and cardiovascular disease. For this reason, experimental atherosclerosis is induced by creating high blood cholesterol in animals. However, the hypothesis that atherosclerotic processes are mostly caused by immune (autoimmune) mechanisms has recently been gaining traction. At the same time, no experimental model has been developed that clearly demonstrates the autoimmune mechanism by which atherosclerosis develops and reproduces the full picture of atherosclerosis solely by means of an immune response, without resorting to additional interventions such as a high‐cholesterol diet or the use of genetic models of hyperlipidemia. Previously, we were able to induce atherosclerosis‐like lesions in the aorta and the development of pericardial fat in rats by immunizing them with human native lipoproteins. The purpose of this study was to test whether atherosclerosis can be induced in normocholesterolaemic rabbits by immunizing them with human native high‐density lipoproteins (hnHDL).MethodsRabbits were immunized with hnHDL. Aortic wall structure, plasma cholesterol level, and antibodies against HDL were studied.ResultsImmunization with hnHDL was found to cause atherosclerosis‐like lesions in the rabbit aorta such as adipocytic and chondrocytic metaplasia, proteoglycan deposits, leukocytic infiltration. Atherosclerosis‐like lesions developed in the aorta of hnHDL‐immunized rabbits against a background of normal blood LDL‐cholesterol level. Therefore, a high plasma cholesterol level is not the sole cause of atherosclerosis. The immune response against HDL is an independent cause of atherogenesis.ConclusionsA rabbit model of atherosclerosis caused by immunization with hnHDL can be widely used to examine the mechanisms occurring during atherogenesis.

Effect of electroacupuncture on glial fibrillary acidic protein and nerve growth factor in the hippocampus of rats with hyperlipidemia and middle cerebral artery thrombus.

Electroacupuncture (EA) has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia. However, there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects. In this study, EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed. Except for the normal group, rats in other groups were fed a high-fat diet throughout the whole experiment. Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks. Middle cerebral artery thrombus models were induced by pasting 50% FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group. EA1 group rats received EA at bilateral ST40 (Fenglong) for 7 days before the thrombosis. Rats in the EA1 and EA2 groups received EA at GV20 (Baihui) and bilateral ST40 for 14 days after model establishment. Neuronal health was assessed by hematoxylin-eosin staining in the brain. Hyperlipidemia was assessed by biochemical methods that measured total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein in blood sera. Behavioral analysis was used to confirm the establishment of the model. Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region. The results demonstrated that, compared with the model group, blood lipid levels significantly decreased, glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups. The repair effect was superior in the EA1 group than in the EA2 group. These findings confirm that EA can reduce blood lipid, inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis. All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine, China (approval No. BUCM-3-2018022802-1002) on April 12, 2018.

Comparison of transcriptomic changes between zebrafish and mice upon high fat diet reveals evolutionary convergence in lipid metabolism

Hyperlipidemia is an abnormal elevation of lipid level in blood, which affects more than 100 million people in US. Zebrafish has recently emerged as a model to study pathophysiology associated with hyperlipidemia. As a poikilotherm, the innate response toward a high fat diet regimen in zebrafish is likely to be distinct from humans, and therefore, additional caution is warranted to appropriately interpret results obtained from zebrafish model. However, to date, detailed comparative analyses on similarities and dissimilarities between zebrafish and mammals, in particular, at molecular level, have not been reported yet. Here, we identified changes in hepatic specific transcriptomic profiles of zebrafish fed with a high fat diet regimen and comparatively analyzed transcriptomic changes in zebrafish and mice. While a number of previously identified risk factors for human hyperlipidemia has been upregulated in zebrafish fed with a high fat diet regimen, zebrafish hepatic transcriptome does not share high similarity with mice. Despite these differences, KEGG pathway analyses revealed that similar signaling pathways upregulated in zebrafish and mice as a response to a high fat diet. Our data show that these two species may utilize species-specific set of genes to upregulate common signaling pathways, indicating evolutionary convergence between poikilotherm and homeotherm in regulating lipid metabolism and validating the use of zebrafish as a model for human hyperlipidemia and associated diseases.

Abstract 472: Liver X Receptor Ligands Suppress Intestinal Soat2 and Reduce Cholesterol in Mice Fed a High Cholesterol Diet

The nuclear receptors, liver X receptor-alpha and -beta (LXRa and LXRb), were originally identified as orphan members of the nuclear receptor (NR) superfamily that function as heterodimers with the retinoid X receptor (RXR). Both LXRa and LXRb play important roles in cholesterol homeostasis and lipid metabolism and have been implicated in the pathology of several diseases including atherosclerosis, cancer, and obesity. Detailed examination of mice deficient in LXRa have revealed significant information regarding its role in regulating lipid metabolism while pharmacological roles of LXR in metabolism and inflammation have been identified using synthetic agonists. We have identified novel synthetic LXR Inverse Agonists that display the ability to suppress lipogenesis and significantly improve the phenotype of fatty liver diseases in several mouse models. During our previous investigation of LXR inverse agonists and fatty liver, we observed a substantial decrease in LDL and total cholesterol, as well as a significant decrease in soat2 gene expression. Recent basic and clinical studies indicate that soat2 may be a potential therapeutic target for cholesterol regulation and atherosclerosis treatment. Based on our observations, we investigated the effects of tissue-selective LXR inverse agonists on cholesterol regulation with greater intensity. We hypothesized that soat2 may be a novel target of LXR and that selectively suppressing LXR in the liver and/or intestine may lead to lowered cholesterol levels in hyperlipidemic models (n = 12). While our research is currently ongoing, we have validated soat2 as a potential LXR target gene by ChIP in hepatocytes, RNA-Seq experiments, fecal cholesterol excretion experiments, as well as expression assays in LXRa/b double knockout mouse tissues (n = 3). Additional studies in LDLr KO mice indicate that selectively targeting LXR in the gut with inverse agonists significantly decrease total and LDL cholesterol (n=12). We believe that this is an innovative method of targeting hypercholesterolemia and may lead to a new class of atherosclerosis therapeutics.

Pyrogallol-Phloroglucinol-6,6-Bieckolon Attenuates Vascular Smooth Muscle Cell Proliferation and Phenotype Switching in Hyperlipidemia through Modulation of Chemokine Receptor 5.

Hyperlipidemia induces vascular smooth muscle cell (VSMC) proliferation and phenotype switching from contractile to synthetic. This process is involved in arterial remodeling via the chemokine ligand 5 (CCL5)/chemokine receptor 5 (CCR5) pathway. Arterial remodeling is related to atherosclerosis or intimal hyperplasia. The purpose of this study was to evaluate whether pyrogallol-phloroglucinol-6,6-bieckol (PPB) from E. cava reduces VSMC proliferation and phenotype switching via the CCL5/CCR5 pathway. The CCL5/CCR5 expression, VSMC proliferation and phenotypic alterations were evaluated using a cell model of VSMC exposed in hyperlipidemia, and an animal model of mice fed a high-fat-diet (HFD). The expression of CCL5/CCR5 increased in both the cell and animal models of hyperlipidemia. Treatment with PPB decreased CCL5/CCR5 expression in both models. The expression of contractile markers of VSMCs, including alpha-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), and smooth muscle protein 22 alpha (SM22α), were decreased by hyperlipidemia and restored after treatment with PPB. The silencing of CCR5 attenuated the effects of PPB treatment. VSMC proliferation and the intima-media thickness of the aortas, increased with HFD and decreased after treatment with PPB. The VSMC proliferation ratio and messenger ribonucleic acid (mRNA) expression of cell cycle regulatory factors increased in the in vitro model and were restored after treatment with PPB. PPB treatment reduced VSMC proliferation and phenotype switching induced by hyperlipidemia through inhibition of the CCL5/CCR5 pathway.

Novel Mechanism of Cholesterol Transport by ABCA5 in Macrophages and Its Role in Dyslipidemia

Cholesterol homeostasis results from a delicate interplay between influx and efflux of free cholesterol primarily mediated by ABCA1. Here we report downregulation of ABCA1 in hyper-cholesterol conditions in macrophages, which might be responsible for compromised reverse cholesterol transport and hyperlipidemia. Surprisingly, this is countered by the upregulation of a lesser known family member ABCA5 to maintain cholesterol efflux. The relative contribution of ABCA1 and ABCA5 toward cholesterol efflux was evaluated and revealed ABCA5 as the primary efflux mediator under high cholesterol load. These observations were correlated to cholesterol load in circulation in vivo, and we observed an inverse expression profile in mice models of atherosclerosis (ApoE−/−) and hyperlipidemia (PPARα−/−) in response to high cholesterol diet. Observations were further validated in human plasma samples. Simulation studies revealed a unique conformation of ABCA5 proposing a favored route for cholesterol loading onto high-density lipoproteins for reverse cholesterol transport. Thus, our study implicates a functional complementation between these two transporters, formulating an efficient strategy to maintain efflux in cholesterol excess conditions in macrophages.

Protective effects of Artemisia judaica extract compared to metformin against hepatorenal injury in high-fat diet/streptozotocine-induced diabetic rats.

Diabetes mellitus (DM) is one of the most dangerous incurable diseases that affects a large number of people worldwide. Artemisia species have various protective activities and are widely used for the control of diabetes in folkloric medicine. Therefore, the current study was designed to illustrate the protective effect of oral administration of Artemisia judaica extract (AjE) against hepatorenal damage in a high-fat diet/streptozotocin (HFD/STZ) rat model of hyperlipidemia and hyperglycemia. Animals were divided into five groups-control, AjE, HFD/STZ, HFD/STZ-AjE (300mg/kg), and HFD/STZ-MET (100mg/kg)-and treated daily for 28days. The results revealed that STZ-injected rats showed marked hyperglycemia and hypoinsulinemia in addition to high levels of cholesterol, triglycerides, and low- and high-density lipoproteins compared to control rats. Significant elevations in hepatic (AST and ALT) and renal (urea, uric acid, and creatinine) function markers were observed in the serum of diabetic rats. Additionally, STZ injection caused remarkable elevations in lipid peroxidation and nitric oxide levels as well as suppression of antioxidant markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione). Marked elevations in TNF-α and Bax levels with a decline in Bcl-2 levels were detected after STZ injection. Furthermore, TGF-β1 expression levels were significantly upregulated in the liver and kidney tissues. Rats that received AjE or MET showed significant improvement in most of the aforementioned parameters, and the protective efficacy was higher for AjE than for MET. Histopathological screening confirmed the biochemical findings. Conclusively, our results illustrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and antiapoptotic activities of AjE against hepatorenal injury in HFD/STZ-induced diabetes.

Lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemia rats based on lipid metabolism disorder

The animal model of hyperlipidemia in rats was established to investigate the lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemic rats. SD rats were selected as the research object. The rats in normal group were fed with basic diet, and the rats in other groups were fed with high-fat diet to establish hyperlipidemia model. The successfully modeled rats were randomly divided into model group, Danhong Injection low, medium, high dose(1.0, 2.0, 4.0 mL·kg~(-1)) groups, and simvastatin(2.0 mg·kg~(-1)) group. Danhong Injection groups received intraperitoneal administration, and simvastatin group received intragastrical administration, once a day for 4 weeks. At the first, second, third, and fourth weekends after administration, blood was collected from the orbital vein to detect the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C), and then the atherosclerosis index(AI) was calculated. After 4 weeks of administration, the animals were sacrificed, and their heart, liver, spleen, lung, kidney and adipose tissue were extracted and weighed respectively to calculate the organ index of each group. The expressions of acyl-coaoxidase 1(Acox1), adenosine 5'-monophosphate(AMP)-activated protein kinase alpha(AMPK-α), bile salt export pump(BSEP), peroxisome proliferator-activated receptor gamma(PPAR-γ), catalase(CAT) and superoxide dismutase(SOD) mRNA in liver tissues were detected by fluorescence quantitative PCR; the content of cholesteryl ester transfer protein(CETP) and lecithin cholesterol acyltransferase(LCAT) in serum was detected by ELISA. The results showed that as compared with the normal group, the levels of serum TC, TG and LDL-C in the model group were significantly increased, and the level of HDL-C was significantly decreased, indicating that the hyperlipidemia rat model was successfully constructed. As compared with the model group, Danhong Injection could decrease the contents of TC, TG, LDL-C and increase the content of HDL-C in hyperlipidemia rats; reduce the body weight of hyperlipidemia rats, and reduce the liver weight, liver index, fat weight and fat index; it had no significant effect on the main organ indexes such as heart, spleen, lung and kidney; but it could increase the expressions of Acox1, AMPK-α, BSEP, PPAR-γ, CAT and SOD mRNA in liver tissues of rats; it could also reduce the level of CETP and increase the level of LCAT in serum; and the regulatory effect of Danhong Injection groups all showed a dose-dependent effect. It can be concluded that Danhong Injection can regulate the blood lipid contents, reduce the blood lipid levels and alleviate the accumulation of body fat in rats with hyperlipidemia. The mechanism may be related to inhibiting lipid metabolism disorder and oxidative stress induced by high-fat diet feeding, and improving the imbalance of lipid transport system.

Dose-dependent beneficial and harmful effects of berberine on mouse oocyte maturation and fertilization and fetal development.

Previous studies have shown that berberine, an isoquinoline alkaloid isolated from several traditional Chinese herbal medicines, suppresses growth and induces apoptosis in some tumor cell lines. It has also been shown that berberine possesses anti-atherosclerosis and antioxidant activities in hyperlipidemic model rats. Our previous study in mice found that berberine causes harmful effects on preimplantation and postimplantation embryonic development, both in vitro and in vivo, by triggering reactive oxygen species (ROS)-mediated apoptotic cascades in mouse blastocysts. In the current investigation, we further showed that berberine treatment has distinct dose-dependent effects on oocyte maturation and subsequent development. Preincubation of oocytes with 2.5μM berberine significantly enhanced maturation and in vitro fertilization (IVF) rates, with subsequent beneficial effects on embryonic development. In contrast, preincubation with 10μM berberine negatively impacted mouse oocyte maturation, decreased IVF rates and impaired subsequent embryonic development. Similar dose-dependent effects were also demonstrated in vivo. Specifically, intravenous injection of berberine significantly enhanced mouse oocyte maturation, IVF rate and early-stage embryo development after fertilization at a dose of 1mg/kg body weight but significantly impaired oocyte maturation and IVF rates and caused harmful effects on early embryonic development at a dose of 5mg/kg. Mechanistically, we found that berberine enhanced intracellular ROS production and apoptosis of oocytes at a concentration of 10μM but actually significantly decreased total intracellular ROS content and had no apoptotic effect at a concentration of 2.5μM. Moreover, pretreatment of oocytes with Ac-DEVD-cho, a caspase-3-specific inhibitor, effectively blocked berberine-induced negative impacts on oocyte maturation, fertilization and subsequent development. Collectively, these findings establish the dose-dependent beneficial versus deleterious effects of berberine and suggest that the mechanism underlying the deleterious effects of berberine involves a caspase-3-dependent apoptotic process acting downstream of an increase in intracellular ROS levels.

Azelastine a potent antihistamine agent, as hypolipidemic and modulator for aortic calcification in diabetic hyperlipidemic rats model

Aim Our study aimed to illustrate the effect of the antihistaminic drug azelastine on aortic calcification in diabetic hyperlipidemic (DH) rats along with the underlying molecular mechanism. Methods Twenty-four male albino Wistar rats were categorised into four groups. One group received normal rodent chow (normal group), while the other groups were rendered diabetic and hyperlipidemic; one received no drugs and served as a positive control while the other two groups received either azelastine (4 mg/kg) or 10-dehydrogingerdione (10 mg/kg) orally and daily for 8 weeks. Results Azelastine significantly reduced blood glucose, HbA1c and serum ALP, OCN, downregulated apo B, improved the lipid profile (LDL-c decrease and HDL-c increase), attenuated calcium deposition and aortic calcification as compared to control group. 10-DHGD showed comparatively lower effect. Conclusion Anti-calcifying effect of azelastine might be related to upregulation of apo A (HDL-c) and downregulation of apo B mRNA expression indeed good modulator of aortic calcification. Impact Statement Many studies have indicated that high-density lipoprotein-cholesterol (HDL-c) is inversely correlated with atherosclerotic plaque progression and could reduce cardiovascular disease risk. An anti-calcifying effect of HDL-c has been reported and targeting this lipoprotein may therefore be a valuable approach to vascular calcification control. Azelastine is a selective H1 antagonist that was identified to increase mRNA expression of apolipoprotein A. This encouraged us to investigate the effect of azelastine on lipid profile and markers of aortic calcification in DH rats. Our findings showed that azelastine ameliorated aortic calcification and increased apoA expression along with a decline in apo B. This may represent the underlying mechanism while the histopathological findings offered a significant support to the collected biochemical data.

Anti-oxidant and anti-hyperlipidemic effects of cordycepin-rich Cordyceps militaris in a Sprague\u2013Dawley rat model of alcohol-induced hyperlipidemia and oxidative stress

Hyperlipidemia is involved in serious cardiovascular disease, however, synthetic drugs to reduce lipid contents in blood stream have been found to induce serious side effects. In the current study, we compared anti-oxidant and anti-hyperlipidemic effect of Paecilomyces japonica (PJ), Cordyceps militaris (CM) and cordycepin-rich Cordyceps militaris (CMα) in rats induced alcoholic hyperlipidemia (AIH) and oxidative stress. The experimental groups were divided in N (water), C (30% alcohol), PJ (30% alcohol + 3% PJ powder), CM (30% alcohol + 3% CM powder), CMα (30% alcohol + 3% CMα powder) and SM [30% alcohol + 0.1% silymarin (SM)]. Compared to C group, supplementation of PJ, CM, CMα and SM slightly alleviated the increased weight ratio of liver and kidney in the alcohol-treated rats. In addition, a significant or slight reduction was identified in total lipid, total cholesterol and HDL-cholesterol levels in the rats receiving PJ, CM and CMα as compared with C group. Administration of PJ, CM and CMα also blocked alcohol-induced lipid peroxidation via a decrease of malondialdehyde (MDA), and activated anti-oxidant enzyme, glutathione (GSH), in serum and various organ tissues. Overall, cordycepin-rich CMα showed highest anti-oxidant and anti-hyperlipidemia effect under chronic alcoholic damage. Our results indicate that CMα might be useful in inhibiting the oxidation and hyperlipidemia in alcohol-induced hepatic disease possibly because of potential anti-oxidative and anti-hyperlipidemic activities of cordycepin.

The potency of green grass jelly extract (Premna oblongifolia Merr) as antihyperlipidemia towards aorta histopathology representation of rat (Rattus norvegicus) induced with high fatty diet (HFD)

Green grass jelly (Premna oblongifolia merr) is a plant containing fiber and chlorophyll which can lower cholesterol and triglyceride levels. This study have aims to investigate the potency of green grass jelly extract (Premna oblongifolia Merr) to prevent hyperlipidemia. The animal mode used for this study is male Rattus norvegicus, Wistar strain, the age of 8 weeks, and weight of 200 g which is divided into 5 groups of treatment namely group Kn (negative control), Kp (positive control), Kp1, Kp2, and Kp3 induced with HFD and green grass jelly extract at a dose of 5.27 g/ kg BW/ daily, 8.43 g/ kg BW/ daily, 9.37 g/ kg BW/ daily. The data of infiltrating fatty cells and macrophage on aorta histopathology was analyzed by description. This research showed that the treatment of green grass jelly extract (Premna oblongifolia Merr) to animals of hyperlipidemia model reduced infiltration fatty cells and macrophage. The conclusion of this study was the green grass jelly extract was able to prevent an increase of fatty cells and macrophage infiltration of rat (Rattus noervegicus) induced with HFD on dose 9.37 g/ kg/ BW/ daily.

Perindopril ameliorates experimental Alzheimer's disease progression: role of amyloid β degradation, central estrogen receptor and hyperlipidemic-lipid raft signaling.

Accumulating evidence indicates that over-stimulation of angiotensin-converting enzyme 1 (ACE1) activity is associated with β-amyloid (Aβ) and phosphorylated tau (p-tau)-induced apoptosis, oxido-nitrosative neuroinflammatory stress and neurodegeneration in Alzheimer's disease (AD). Alternatively, activation of the ACE2, the metalloprotease neprilysin (Neutral Endopeptidase; NEP) and the insulin-degrading enzyme (IDE) could oppose the effects of ACE1 activation. We aim to investigate the relationship between ACE1/ACE2/NEP/IDE and amyloidogenic/hyperlipidemic-lipid raft signaling in hyperlipidemic AD model. Induction of AD was performed in ovariectomized female rats with high-fat high fructose diet (HFFD) feeding after 4weeks following D-galactose injection (150mg/kg). The brain-penetrating ACE1 inhibitor perindopril (0.5mg/kg/day, p.o.) was administered on a daily basis for 30days. Perindopril significantly decreased hippocampal expression of ACE1 and increased expression of ACE2, NEP and IDE. Perindopril markedly decreased Aβ1-42, improved lipid profile and ameliorated the lipid raft protein markers caveolin1 (CAV1) and flotillin 1 (FLOT1). This was accompanied by decreased expression of p-tau and enhancement of cholinergic neurotransmission, coupled with decreased oxido-nitrosative neuroinflammatory stress, enhancement of blood-brain barrier (BBB) functioning and lower expression of the apoptotic markers glial fibrillary acidic protein (GFAP), Bax and β-tubulin. In addition, perindopril ameliorated histopathological damage and improved learning, cognitive and recognition impairment as well as depressive behavior in Morris water maze, Y maze, novel object recognition and forced swimming tests, respectively. Conclusively, perindopril could improve cognitive defects in AD rats, at least through activation of ACE2/NEP/IDE and inhibition of ACE1 and subsequent modulation of amyloidogenic/hyperlipidemic-lipid raft signaling and oxido-nitrosative stress.

Effects of different transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, HSL and HMG-CoA reductase in hyperlipidemia rabbits

To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids, hormone-sensitive lipase (HSL) and hydroxymethylglutaryl CoA (HMG-CoA) reductase in hyperlipidemia rabbits. Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method, with 8 rats in each group. Rabbits in the blank group were fed routinely with a normal diet; rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model. Rabbits in the blank and the model groups were not given any intervention. After the model was prepared successfully, rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers; rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively. After 4 weeks of treatment, the serum was isolated and enzyme-linked immunosorbent assay (ELISA) was applied for the detection of HSL and HMG-CoA reductase. The liver tissues were isolated, and total cholesterol (TC) and triglycerides (TG) were measured by enzymatic methods. One-step method was applied for high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) detection, and transmission turbidimetry was for apolipoprotein A1 (Apo-A1) and apolipoprotein B (Apo-B) detection. The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group (both P<0.05); all drug penetrations in the borneol group were significantly higher than those in the laurocapram group (both P<0.05), except for tanshinone IIA. Compared with the non-transdermal penetration enhancer group, the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups (both P<0.05); between groups, the HSL in the borneol group was significantly higher than that in the laurocapram group (P<0.05). Compared with the blank group, the levels of LDL-C, TG, TC and Apo-B in rabbit liver were significantly increased in the model group (P<0.05); compared with the model group, the levels of LDL-C, TG, TC and Apo-B in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups were significantly decreased (all P<0.05); between groups, the TG and TC in the laurocapram group and the LDL-C, TG, TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group (all P<0.05), and the TG, LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group (all P<0.05). Compared with the blank group, the HDL-C and Apo-A1 were significantly decreased in the model group (both P<0.05), while compared with the model group, the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer, the laurocapram, and the borneol groups (all P<0.05). Between groups, the Apo-A1 in the laurocapram group, the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group (all P<0.05). The application of laurocapram and borneol, as transdermal penetration enhancers, in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake, increase the levels of HDL-C and Apo-A1, improve the metabolism of HSL and HMG-CoA reductase, and also simultaneously reduce the levels of TC, TG, LDL-C and Apo-B in the liver. The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.

Baicalein maintains redox balance in experimental hyperlipidemic rats

Context: An altered lipid profile may lead to the development of CVD.Objective: We evaluated the protective role of baicalein (BAC) against lipidemic and oxidative stress in hyperlipidemic challenged Wistar rats.Materials and methods: Male Wistar rats were given a high-fat diet (HFD) (suspension (w/v) of 0.5% cholesterol, 3% coconut oil and 0.25% cholic acid for 30 days) to create a hyperlipidemic model. BAC was supplemented to experimental rats (80 mg/kg body weight). Biomarkers of oxidative stress including ROS, FRAP, GSH, PMRS, AGE, MDA, PCO, AOPP, and other parameters (Paraoxonase-1, SGOT, SGPT) including TNF-α and IL-6, were estimated in blood.Results: Oxidative stress and inflammatory markers were significantly increased in the HFD treated group. BAC treatment protected rats from HFD mediated alterations.Discussion & conclusion: Our results indicate that baicalein provides protection against hyperlipidemic stress and redox imbalance induced by HFD in rats.

Supplements of an aqueous combination of Justicia adhatoda and Ocimum tenuiflorum boost antioxidative effects and impede hyperlipidemia.

Background Justicia adhatoda and Ocimum tenuiflorum, locally known as bashok and tulsi, are two ethnomedicinally important herbs that have been using as dietary supplements for several therapeutic applications. This study evaluated the combined effect of both the herbs as an antioxidative and antihyperlipidemic agent.MethodsAntihyperlipidemic effect was assessed in a high‐fat diet‐induced hyperlipidemic model in Wistar albino rats. The rats were treated orally with extracts of bashok (J adhatoda, 200 mg/kg bw), tulshi (O tenuiflorum, 200 mg/kg bw), and a combination of bashok and tulshi (50:50), as well as with a reference drug, atorvastatin (10 mg/kg/day), with or without high‐fat diet for 14 days. The antioxidative effect was studied using established in vitro models. The studies were supported by experimentally testing the effects of the extracts on membrane stabilization and inhibition of protein denaturation.ResultsThe results showed that the serum lipid profile was significantly decreased in the different treatment groups, with bashok having the greatest effect. Body weights, total serum protein, LDH, and relative liver and adipose tissue weights were markedly restored towards baseline values, the lowest atherogenic index being achieved with the combined extract. The combination treatment significantly enhanced total phenolic content and antioxidative capacity and greatly potentiated membrane stabilization, but inhibition of protein denaturation was not significantly affected.ConclusionThe data demonstrate that a combination of Justicia adhatoda and Ocimum tenuiflorum could be developed as a food supplement with antioxidative and antihyperlipidemic benefits.