Antihyperlipidemic Effects Research Articles

Hypolipidemic and Hypoglycemic Effects of Silybum marianum (L.) Gaertn.(Milk Thistle) Ethanol Seed Extract in Streptozotocin-induced Diabetes in Rats

Background: Metabolic syndrome (MS) is considered a challenging health problem worldwide. However, the search for alternative treatments to alleviate MS is lacking. Purpose: This study defines Silybum marianum (milk thistle) ethanol seed extract (SMESE) in terms of polyphenol and flavonoid content, antiglycation effect, α-amylase activity, and hypolipidemic and hypoglycemic effects in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: S. marianum seeds were collected, ground, and extracted with 80% ethanol. The α-amylase inhibitory activities of 10, 30, and 100 µg/mL SMESE were evaluated using spectrophotometric methods. The inhibitory activity of SMESE against advanced glycation end-product formation was evaluated using fluorescence spectrophotometry. In vivo, 48 Wistar male albino rats were used. Eight animals served as the normal control (group 1), and 40 rats were injected with 60 mg/kg STZ to induce diabetes. Diabetic rats were divided into five groups: diabetic control (group 2) and positive control that received the hypoglycemic reference drug metformin at 100 mg/kg (group 3). Groups 4, 5, and 6 were administered the seed extract orally at 30, 100, and 300 mg/kg, respectively. Body weight, serum glucose, lipid profile, and malondialdehyde (MDA) levels were measured weekly for five weeks after SMESE administration. Results: SMESE administration inhibited BSA glycation and α-amylase activity. In vivo, SMESE administration increased body weight (BW), decreased serum glucose levels, and reduced triglyceride, total cholesterol, low-density lipoprotein, very low-density lipoprotein, and MDA levels but increased high-density lipoprotein levels. Conclusion: Data indicate the beneficial hypoglycemic and antihyperlipidemic effects of SMESE, suggesting its potential use in controlling lipid metabolism.

Influence of Mid-Infrared Irradiation on Amla’s (<i>Phyllanthus emblica</i>) Physicochemical Properties and Acceptability Index

Amla (<i>Phyllanthus emblica</i>), commonly known as Indian gooseberry, is highly esteemed for its nutritional and medicinal properties. It possesses a rich abundance of bioactive compounds and exhibits a wide range of health benefits, including anti-hyperlipidemic, antidiabetic, anticancerous, anti-inflammatory, hepatoprotective, and neuroprotective effects. Amla lends itself to the production of diverse value-added goods such as powder, candy, juice, soup, and oil, offering a convenient and nutritious means of incorporating this fruit into one's daily regimen. Earlier studies suggest that irradiation can have both positive and negative effects on amla, depending on the specific parameters and doses used. Therefore, the primary aim of the present study was to positively enhance the inherent characteristics of amla by employing the safe and effective 2-6 µm mid-infrared rays, thereby further augmenting its value. Our research utilized a water-based atomizer known as the 2-6µm mid-infrared radiation generating atomizer (MIRGA), which was recently developed by us. A panel of sensory experts conducted a thorough assessment of amla both before and after the application of mid-IR radiation. In addition, various analytical techniques, including FTIR, PXRD, TEM, and H1NMR, were employed to further characterize the irradiated amla. The results demonstrated that the application of mid-IR radiation positively influenced the sensory attributes of amla, enhancing its palatability. Furthermore, the findings revealed significant transformations at the atomic, bond, and compound levels. Hence, it can be inferred that the utilization of mid-IR radiation through an economical, easily accessible, and safe technology holds immense potential for elevating the quality of amla.

Lactic acid bacteria-malted vinegar: fermentation characteristics and anti-hyperlipidemic effect.

In this study, the fermentation characteristics and functional properties of lactic acid bacteria-malted vinegar (LAB-MV) were investigated during the fermentation period. Changes in the components (organic acids, free sugars, free amino acids, β-glucan, and gamma-aminobutyric acid (GABA)) of MV (BWAF0d, BWAF10d, BWAF20d) and LAB-MV (LBWAF0d, LBWAF10d, LBWAF20d) were analyzed according to the fermentation time. The amounts of β-glucan and GABA in LBWAF20d were greater than those in BWAF20d (122.00μg/mL, 83.06μg/mL and 531.00μg/mL, 181.31μg/mL, respectively). The ACE1 and HMG-CoA reductase inhibitory activities of LBWAF20d were 98.16% (1/20 dilution factor, DF) and 91.01% (1/25 DF), respectively. The lipid accumulation ratio and total cholesterol levels in HepG2 cells treated with LBWAF20d (1/200 DF) were reduced by 45.85% and 54.48%, respectively, compared to those in the untreated group. These results suggest that LAB-MV, which comprises barley wine manufactured from LAB and yeast, may improve hepatic lipid metabolism.

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%–50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P < 0.05). The treatment intake has also shown a significant effect to modulate the altered hepatic and renal biomarkers. Further treatment with thiazolidine-2,4-dione derivatives for 28 days significantly ameliorated changes in appearance and metabolic risk factors, including favorable changes in histopathology of the liver, kidney, and pancreas compared with the HFD/STZ-treated group, suggesting its potential role in the management of diabetes. Thiazolidine-2,4-dione derivatives are a class of drugs that act as insulin sensitizers by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that regulates glucose and lipid metabolism. The results of this study suggest that thiazolidine-2,4-dione derivatives may be a promising treatment option for T2DM by improving glycemic control, lipid metabolism, and renal and hepatic function.

Laminaria japonica Aresch-Derived Fucoidan Ameliorates Hyperlipidemia by Upregulating LXRs and Suppressing SREBPs.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and hyperlipidemia is one major inducing factor of CVD. It is worthy to note that fucoidans are reported to have hypolipidemic activity with species specificity; however, the underlying mechanisms of action are far from clarification. This study is aimed at investigating the plasma lipid-lowering mechanisms of the fucoidan from L. japonica Aresch by detecting the levels of hepatic genes that are involved in lipid metabolism. Our results demonstrated that the fucoidan F3 significantly lowered total cholesterol and triglyceride in C57BL/6J mice fed a high-fat diet. In the mouse liver, fucoidan F3 intervention significantly increased the gene expression of peroxisome proliferator-activated receptor (PPAR) α, liver X receptor (LXR) α and β, and ATP-binding cassette transporter (ABC) G1 and G8 and decreased the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, cholesterol 7 alpha-hydroxylase A1, and sterol regulatory element-binding protein (SREBP) 1c and SREBP-2. These results demonstrated that the antihyperlipidemic effects of fucoidan F3 are related to its activation of PPARα and LXR/ABC signaling pathways and inactivation of SREBPs. In conclusion, fucoidan F3 may be explored as a potential compound for prevention or treatment of lipid disorders.

Ezetimibe-Loaded Nanostructured Lipid Carrier for Oral Delivery: Response Surface Methodology; In Vitro Characterization and Assessing the Antihyperlipidemic Effect in Rats.

Among the independent risk factors for the occurrence of cardiovascular diseases like atherosclerosis is hyperlipidemia. To decrease cardiovascular events and patient mortality, antihyperlipidemia therapy is crucial. Our study aimed to enhance the solubility of the poorly soluble lipid-lowering agent ezetimibe (EZ), a member of class II as per the Biopharmaceutics Classification System (BCS). The drug was formulated as a nanostructured lipid carrier (NLC) employing the ultrasonication technique. A response surface D-optimal design was employed to study the effect of changing the liquid lipid type and the percentage of liquid lipid with respect to total lipid amount on the particle size, zeta potential, percentage entrapment efficiency, and percentage of drug released after 24 h. Nine NLC formulations were prepared and pharmaceutically evaluated, and the optimized NLC formulation was selected, further characterized, and evaluated as well. Optimized EZ-NLC was assessed in the high-fat diet model to induce hyperlipidemia in rats in comparison with the EZ suspension. The results of the optimized formulation showed that the prepared NLCs were spherical with no aggregation having a particle size of 204.3 ± 19.17 nm, zeta potential equal to -32 ± 7.59 mV, and entrapment efficiency of 81.5 ± 3.58% and 72.15 ± 4.58% drug released after 24 h. EZ-NLC significantly decreased the elevated serum lipid parameters, including total cholesterol, triglycerides, and LDL-C, but significantly normalized serum HDL-C levels of rats kept on a high-fat diet. The results demonstrated the improved efficacy of EZ-NLC in ameliorating the elevated serum lipid parameters compared to EZ.

Vitamin D was Superior to Omega-3 as a Simvastatin Adjuvant in Improving Blood Lipids and Atherogenic Index in Type-I Dyslipidemic Rats.

Adjuvant therapy is often used to optimize the antihyperlipidemic effect of simvastatin. Omega-3 and vitamin D supplementation are recommended as adjuvant therapies to low-intensity statins. This study aimed to compare the effects of vitamin D and omega-3 as adjuvant therapy to simvastatin to improve the lipid profiles and atherogenic index of plasma (AIP) in type-I dyslipidemic rats. Thirty-six male rats were randomized and divided into six groups: healthy control, dyslipidemic rats with no treatment, and dyslipidemic rats treated with either low-dose simvastatin only or omega-3 or vitamin D at low and high doses. Dyslipidemia was induced with high-fat diets for four weeks, followed by treatment for the next two weeks. Blood samples were withdrawn before and after simvastatin treatment. In addition, aspartate transaminase (AST) and alanine transaminase (ALT) levels were analyzed to assess liver function. Administration of a high-fat diet-induced type 1 dyslipidemia and increased ALT levels (p < 0.05). Treatment with low-dose simvastatin did not significantly improve triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc) or non-HDLc levels. When combined with a high-dose vitamin D, simvastatin significantly reduced TG and increased HDLc levels (p < 0.05), thereby improving AIP levels. This improvement was not observed in rats treated with omega-3 or vitamin D at a lower dose. We concluded that high-dose vitamin D as an adjuvant to simvastatin therapy was superior to omega-3 in improving TG, HDL, and AIP levels. High-dose vitamin D also improved ALT levels in type-I dyslipidemic rats. This result may be translated in clinics to reduce the risk of coronary syndrome in patients with type-I dyslipidemia.

Effect of Justicia schimperiana (Acanthaceae) roots extract on blood glucose level and lipid profiles in streptozotocin-induced diabetic mice

BackgroundJusticia schimperiana has been used traditionally for the treatment of different diseases, including, diabetes. Yet, no in vivo study was conducted to substantiate these claims. This study aimed to evaluate the effect of Justicia schimperiana roots extract on blood glucose levels and lipid profiles in streptozotocin-induced diabetic mice. MethodsMale Swiss albino mice weighing 25–35 g were induced diabetes with 150 mg/kg of STZ. Animals were randomly grouped into six groups of five each. Group I was a normal control, Group II was a Diabetic control, Group III–V were Diabetic Mice treated with the extract (100, 200, and 400 mg/kg) respectively, and Group VI was standard control. The treatments were followed for 14 days. The FBG measurements were done on 0, 7th, and 14th days of treatment. On the 15th day, the mice were anesthetized with diethyl ether; blood samples were collected for the assessment of serum lipid profiles. The antioxidant and α-amylase inhibitory activities of the extract were also investigated in vitro using the DPPH and DNSA assay methods, respectively. The data were entered into EPI DATA version 4.6, exported to IBM, SPSS version 26.0, and analyzed using a one-way ANOVA followed by Tukey's post hoc test. P < 0.05 was considered statistically significant. ResultsThe hydromethanolic extract of J. schimperiana roots exhibited no toxicity up to a dose of 2000 mg/kg body weight. In the STZ-induced diabetic mice, the extract reduced blood glucose levels at all tested doses: 100, 200, and 400 mg/kg on the 14th day as compared to diabetic control. The higher dose showed maximum reduction (29.73 %, p < 0.001) on the 14th day of treatment compared to the baseline. There were significant reductions in serum TG, TC, LDL, and a significant increase in body weight and HDL compared to the diabetic control. Besides, good antioxidant and α-amylase inhibitory activity were obtained from the in vitro laboratory tests. ConclusionsEvidence from our study revealed that the root extract of J. schimperiana has antihyperglycemic and antihyperlipidemic effects in STZ-induced diabetic mice.

Formulation and evaluation of new herbal nutraceutical tablet for the treatment of diabetes mellitus

Abstract BACKGROUND: Herbal nutraceutical dosage forms a dietary supplement that improves various chronic diseases. This study aimed to formulate and evaluate new herbal nutraceutical tablets and assess antihyperglycemic and antihyperlipidemia effects in ob/ob mice. METHODS: A herbal nutraceutical tablet was prepared by the wet granulation method. Proximate composition was determined by the Association of Official Analytical Chemists methods. The high-performance liquid chromatography method was used for the estimation of water-soluble vitamins and fat-soluble vitamins. An atomic absorption spectrophotometer was used for analyzing trace elements. Oral glucose tolerance tests and biochemicals were analyzed to assess antihyperglycemic and antihyperlipidemia effects in ob/ob mice. RESULTS: Herbal nutraceutical tablet contains a good amount of energy. Iron, sodium, potassium, phosphorus, magnesium, iodine, copper, zinc, and calcium were present in the newly formulated herbal tablets. A reasonable amount of water-soluble and fat-soluble vitamins were also present. Administration of newly developed herbal nutraceutical tablets (200 mg/kg) in ob/ob mice significantly improved the antihyperglycemic and antihyperlipidemia effects compared to the standard drug metformin (200 mg/kg). CONCLUSIONS: Based on these findings, a newly formulated herbal nutraceutical tablet may be recommended as a dietary supplement and can be utilized as an active type 2 diabetes drug.

Anti-hyperglycemic and anti-hyperlipidemic effects of a methanolic extract of Debregeasia salicifolia in Alloxan-induced diabetic albino mice.

Diabetes mellitus (DM), an endocrine syndrome characterized by high blood glucose levels due to abrogated insulin activity. The existing treatments for DM have side effects and varying degrees of efficacy. Therefore, it is paramount that novel approaches be developed to enhance the management of DM. Therapeutic plants have been accredited as having comparatively high efficacy with fewer adverse effects. The current study aims to elucidate the phytochemical profile, anti-hyperlipidemic, and anti-diabetic effects of methanolic extract D. salicifolia (leaves) in Alloxan-induced diabetic mice. Alloxan was injected intraperitoneally (150 mg kg-1, b.w), to induced diabetes in mice. The mice were divided into three groups (n=10). Group 1 (normal control) received normal food and purified water, Group II (diabetic control) received regular feed and clean water and group III (diabetic treated) received a methanolic extract of the plant (300 mg kg-1) for 28 days with a typical diet and clean water throughout the experiment. Blood samples were collected to checked serum glucose and concentration of LDL, TC, TG. The extract demonstrated significant antihyperglycemic activity (P<0.05), whereas improvements in mice's body weight and lipid profiles were observed after treatment with the extract. This study establishes that the extract has high efficacy with comparatively less toxicity that can be used for DM management.

Promotion of neuroinflammation by the glymphatic system: a new insight into ethanol extracts from Alisma orientale in alleviating obesity-associated cognitive impairment.

Obesity is one of the critical risk factors for cognitive dysfunction. The glymphatic system (GS) plays a key role in the pathogenesis of cognitive deficits. Alisma orientale has been shown to have anti-inflammatory and antihyperlipidemic effects, whereas its effects and underlying mechanisms on obesity-associated cognitive impairment (OACI) are unclear. This work aims to decipher the mechanism of ethanol extracts from Alisma orientale (EEAO) in restoring cognitive impairment in HFD-induced obese mice through a GS approach. The restoration of abnormal glucose/lipid metabolism and excess adipose deposition by EEAO were assayed by biochemical analysis and visually displayed by a micro-CT scanner and Oil Red O staining. Biochemical assays and Western blotting (WB) were used to measure cerebral blood flow (CBF), free fatty acid (FFAs) levels and the structural integrity of the blood-brain barrier (BBB). Microglial activation and neuroinflammation were assessed with immunohistochemistry staining, ELISA and WB. Moreover, GS function was determined by immunofluorescence staining, fluorescence tracer imaging and WB. Finally, the neuropathological features and cognitive functions were detested with immunohistochemistry staining, immunofluorescence and Morris Water Maze. EEAO not only alleviated body weight, cerebral lipid accumulation and serum FFAs in HFD-induced obese mice, but also increased CBF and BBB integrity. EEAO suppressed microglial activation and lipid deposition in the hippocampus and reduced the level of inflammatory cytokines including IL-6, IL-1β and TNF-α in brain tissue. Interestingly, long-term HFD-induced GS dysfunction was significantly restored after EEAO intervention, and neuropathological lesions and cognitive deficits were also markedly rescued. EEAO rescued the cognitive deficits of OACI by inhibiting neuroinflammation and restoring GS dysfunction, indicating a potential remedy for OACI.

Anti-adipogenic effect of Malva parviflora on 3T3-L1 adipocytes.

Malva parviflora has shown anti-inflammatory, antihypertensive, antihyperlipidemic, and hypoglycemic effects. This study is aimed to evaluate the anti-adipogenic effect of M. parviflora on 3T3-L1 adipocytes. Fibroblast differentiation was induced either in the absence or presence of M. parviflora fractions (F3, F4, F7, F12, F13, F17, F18 and F19) for 4 days; F17 and 18 were the most effective fractions in reducing intracellular lipid accumulation (by 25.6% and 23.1%, respectively). EC50 of F17 and F18 (14 μg/mL and 17 μg/mL, respectively) were used to evaluate their anti adipogenic effect. After 10 days of inducing differentiation in the absence or presence of the extracts at the EC50 of F17 and F18, lipid accumulation, the concentration of interleukin 6 (IL-6) were measured in the culture medium; the presence of PPAR-γ, AKT, and p-AKT was also determined. In differentiated adipocytes (C2), F17 maintained intracellular lipid concentration at levels comparable to metformin, while decreasing PPAR-γ and increasing p-AKT presence; it also prevented IL-6 expression. F17 consists of alanine, valine, phenylalanine, and proline. On the other hand, F18 reduced intracellular lipid concentrations, prevented the increase of PPAR-γ and p-AKT, and maintained IL-6 expression at similar levels as metformin. F18 is mainly constituted by alanine, valine, proline, and sucrose. In conclusion, M. parviflora fractions (F17 and F18) control the process of adipogenesis, lipogenesis, and cellular dysfunction.

Exploring the efficacy of the wild mushroom Astraeus hygrometricus extract on lipid profiles, insulin resistance, and oxidative stress in rats fed a high-fat diet

Edible wild mushrooms are considered to contain healthy bioactive ingredients that exert various pharmacological effects. We aimed to determine the antihyperlipidemic, antihyperglycemic, and antioxidant effects of the wild mushroom Astraeus hygrometricus (A. hygrometricus) extract in a rat model of dyslipidemia induced by a high-fat diet (HFD). Experimental rats received an HFD with or without A. hygrometricus extract (500 mg/kg body weight) or simvastatin (10 mg/kg body weight, a positive control) for 63 days. Oral administration of the extract decreased the blood glucose, glycated hemoglobin, triglyceride, and low-density lipoprotein cholesterol levels; counteracted insulin resistance; and increased the high-density lipoprotein cholesterol levels in HFD-fed rats. These changes were accompanied by a decrease in serum malondialdehyde and an increase in the activities of superoxide dismutase and glutathione peroxidase, two major antioxidant enzymes. Overall, A. hygrometricus extract supplementation alleviates hyperglycemia and hyperlipidemia in HFD-fed rats by decreasing insulin resistance and reducing oxidative stress.

Antihyperlipidemic and Antiobesity Effects of Parmotrema tinctorum Ethanolic Extract in Olive Oil-Induced Hyperlipidemic Rats

Antihyperlipidemic and Antiobesity Effects of Parmotrema tinctorum Ethanolic Extract in Olive Oil-Induced Hyperlipidemic Rats

Protective effects of silymarin-loaded chitosan nanoparticles in the diet-induced hyperlipidemia rat model.

Obesity is a metabolic syndrome that leads to many chronic diseases worldwide. In this study, we investigate the antihyperlipidemic activities of chitosan nanoparticles (CH NPs) on silymarin (SIL) as a carrier in the drug delivery system that can improve some biochemical parameters and hormones in the model of hyperlipidemic rats receiving a high-fat diet (HFD). Physicochemical characterization of silymarin-loaded chitosannanoparticles (CH-SIL NPs) was done by Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and drug loading efficiency (LE). Diet-induced hyperlipidemic rats were treated with SIL (15 mg/kg/day) and CH-SIL NPs(15 mg/kg/day) for twelve weeks orally daily. The body weight loss (BW), food consumption, serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), levels of fasting blood glucose (FBG) in serum, serum insulin, cortisol, testosterone, and brain neuropeptide Y (NPY), Y1 and Y5 receptor mRNA expression were analyzed. A significant reduction in BW and food consumption from 417 ± 16 g and 33 ± 1.03 in group HFD to 338 ± 10 g and 17.33 ± 1.02 in group CHS+HFD was observed, respectively. This data revealed that CH-SIL NPs improved hyperlipidemia, hyperinsulinemia, and hyperglycemia, reduced serum cortisol, and down-regulated NPY and Y1R with a significant increase in HDL and testosterone hormones compared to the control group. The developed Sil-loaded CH NPs were good agents for improving efficacy. It is the first report of the proposed weight loss mechanism of SIL CH NPs, thereby providing information about the anti-hyperlipidemic and antihyperglycemic effects of silymarin-loaded chitosan nanoparticles, a natural food with proper effects against metabolic disorders in case of hyperlipidemia that may lead to obesity and up-regulation of brain NPY.

The comparison of the antidiabetic effects of exenatide, empagliflozin, quercetin, and combination of the drugs in type 2 diabetic rats.

Type 2 diabetes, a metabolic disease that involves extended treatment, is rapidly increasing in humans and animals worldwide. This study aimed to compare monotherapy and combined therapy of exenatide, empagliflozin, and quercetin in 67 Wistar Albino male rats. The animals were divided into the following seven groups: healthy control, diabetes control, diabetes + sham, diabetes + exenatide (10μg/kg), diabetes + empagliflozin (50 mg/kg), diabetes + quercetin (50 mg/kg), and diabetes + combination treatment. The treatments were continued for 8 weeks. At the end of the experiment, glucose and HbA1c levels decreased with all monotherapy treatments and the combination treatments, while insulin levels increased with exenatide and combined treatments. Adiponectin levels increased with empagliflozin, quercetin, and combined treatments, while leptin levels decreased only with combined treatments. All monotherapies caused an increase in total antioxidant levels. Exenatide and quercetin treatments reduced low-density lipoprotein (LDL) levels; therewithal, exenatide and combined treatments increased high-density lipoprotein (HDL) levels. Triglyceride levels decreased in all treatment groups. The homeostatic model assessment for insulin resistance (HOMA-IR) level decreased with the combined treatment; on the contrary, the homeostatic model assessment for β-cell activity (HOMA-β) level increased with empagliflozin, exenatide, and combined treatments. In conclusion, the antidiabetic effects of exenatide were more pronounced than empagliflozin and quercetin, however, the combined treatment had better antidiabetic and antihyperlipidemic effects than monotherapies. Quercetin could be a supportive or food supplement antidiabetic agent. The exenatide treatment can be recommended for monotherapy in type 2 patients, and the combination of empagliflozin, exenatide, and quercetin may be effective in diabetic patients who need combined therapy.

Active peptides from Eupolyphaga sinensis walker attenuates experimental hyperlipidemia by regulating the gut microbiota and biomarkers in rats with dyslipidemia

Eupolyphaga sinensis Walker (ESW) is a traditional Chinese medicine formulation used to treat hyperlipidemia. However, the hypolipidemic effect of the active peptides from E. sinensis Walker (APE) is incompletely understood. We studied the hypolipidemic effect of APE and explored the impact of APE on the gut microbiota (GM) in rats suffering from hyperlipidemia. APE was prepared by enzymatic digestion, and its structure was characterized using various methods. The anti-hyperlipidemic activity of APE was assessed using a high-fat diet (HFD)-induced model in zebrafish and rats. In rats, HFD administration caused abnormalities of lipid metabolism and disturbances of the GM and amino acid (AA) profile in plasma. The abundance of bacteria of the phyla Firmicutes and Bacteroides was increased significantly (p < 0.05), and the relative abundance of Lactobacillus species and Clostridium species was decreased significantly (p < 0.05). HFD therapy affected the levels of 12 AAs in vivo: 10 AAs showed increased levels and two AAs had decreased levels (p < 0.05). Similar results were demonstrated in an experiment on fecal microbiota transplantation. APE treatment dose-dependently decreased lipid factors and liver damage (p < 0.05). Sequencing of the 16 S rRNA gene indicated that APE improved the intestinal-flora structure of rats with HL markedly, and increased the relative abundance of Lactobacillus species and Clostridium species. Metabolomics analysis indicated that APE could alter the levels of 10 AAs affected by HFD consumption. Spearman correlation analysis revealed that gamma-aminobutyric acid (GABA) could be a crucial metabolite, and Lactobacillus species and Clostridium species might be important bacteria for the action of APE against hyperlipidemia. We speculate that APE exhibited an anti-hyperlipidemic effect by regulating GABA synthesis in the presence of Lactobacillus species and Clostridium species.

In vivo Evaluation of Berberine-loaded Liposomes in the Exogenous Hyperlipidemia Animal Model

Berberine (BBR) is an alkaloid presenting exogenous cholesterol lowering and anti-hyperlipidemia therapeutic effects in the literature. In this study, the exogenous lipid-lowering effects of oral BBR-loaded liposomes were investigated in rats compared with free BBR within four weeks. The BBR-loaded liposomes at the daily oral dose of 25 mg BBR/kg of body weight in rats reduced total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) by 22.34% (p&gt;0.05), 43.93% (p&lt;0.05), respectively. These values (TC and LDL-C) when rats were given BBR-loaded liposomes at the daily oral dose of 50 mg BBR/kg were 30.72% (p&lt;0.05) and 42.77% (p&lt;0.05) compared with those values of the untreated control group, respectively. Both doses of BBR-loaded liposomes have no signals in decreasing triglycerides.&#x0D; Keywords: Berberine, berberine-loaded liposomes, anti-hyperlipidemia, animal model.&#x0D; &#x0D; &#x0D;

Gemfibrozil Improves Microcirculatory Oxygenation of Colon and Liver without Affecting Mitochondrial Function in a Model of Abdominal Sepsis in Rats.

Recent studies observed, despite an anti-hyperlipidaemic effect, a positive impact of fibrates on septic conditions. This study evaluates the effects of gemfibrozil on microcirculatory variables, mitochondrial function, and lipid peroxidation levels with regard to its potential role as an indicator for oxidative stress in the colon and liver under control and septic conditions and dependencies on PPARα-mediated mechanisms of action. With the approval of the local ethics committee, 120 Wistar rats were randomly divided into 12 groups. Sham and septic animals were treated with a vehicle, gemfibrozil (30 and 100 mg/kg BW), GW 6471 (1 mg/kg BW, PPARα inhibitor), or a combination of both drugs. Sepsis was induced via the colon ascendens stent peritonitis (CASP) model. Then, 24 h post sham or CASP surgery, a re-laparotomy was performed. Measures of vital parameters (heart rate (HR), mean arterial pressure (MAP), and microcirculation (µHbO2)) were recorded for 90 min. Mitochondrial respirometry and assessment of lipid peroxidation via a malondialdehyde (MDA) assay were performed on colon and liver tissues. In the untreated sham animals, microcirculation remained stable, while pre-treatment with gemfibrozil showed significant decreases in the microcirculatory oxygenation of the colon. In the CASP animals, µHbO2 levels in the colon and the liver were significantly decreased 90 min after laparotomy. Pre-treatment with gemfibrozil prevented the microcirculatory aberrations in both organs. Gemfibrozil did not affect mitochondrial function and lipid peroxidation levels in the sham or CASP animals. Gemfibrozil treatment influences microcirculation depending on the underlying condition. Gemfibrozil prevents sepsis-induced microcirculatory aberrances in the colon and liver PPARα-independently. In non-septic animals, gemfibrozil impairs the microcirculatory variables in the colon without affecting those in the liver.

The anti-hyperlipidemic effects of Poria cocos (Schw.) Wolf extract: Modulating cholesterol homeostasis in hepatocytes via PPARα pathway

Ethnopharmacological relevancePoria cocos (Schw.) Wolf (Polyporaceae, P.cocos), which is born on the pine root, has a history of more than two thousand years of medicine in China. P.cocos was first recorded in the Shennong's Herbal Classic, studies have proved its lipid-lowering effect. Aim of studyThe aim of study was to investigate the underlying mechanism of P.cocos extract on hyperlipidemia. Materials and methodsMale Sprague-Dawley (SD) rats aged 9–12 weeks were intraperitoneally (IP) injected with Triton-WR 1339 to establish an acute hyperlipidemia model. At 0 h and 20 h after the model was established, low and high doses of P.cocos extract or simvastatin were given twice. After 48 h, the rats were sacrificed, and liver and serum samples were collected for analysis. The cell model was constructed by treating L02 cells with 1% fat emulsion-10% FBS–RPMI 1640 medium for 48 h. At the same time, low and high doses of P.cocos extract and simvastatin were administered. Oil red O staining was used to evaluate the lipid accumulation in the cells, and H&E staining was used to evaluate the liver lesions of rats. Real-time quantitative PCR and western blotting were used to detect the expressions of lipid metabolism-related genes. ResultsP.cocos extract relieved lipid accumulation in vitro and alleviated hyperlipidemia in vivo. Both gene and protein expressions of peroxisome proliferator-activated receptor α (PPARα) were shown to be up-regulated by P.cocos extract. Additionally, P.cocos extract down-regulated the expressions of fatty acid synthesis-related genes sterol regulatory element-binding protein-1 (SREBP-1), Acetyl-CoA Carboxylase 1 (ACC1) and fatty acid synthase (FAS), while up-regulated the expressions of cholesterol metabolism-related genes liver X receptor-α (LXRα), ATP-binding cassette transporter A1 (ABCA1), cholesterol 7alpha-hydroxylase (CYP7A1) and low density lipoprotein receptor (LDLR), which were reversed by the treatment with the PPARα inhibitor GW6471. ConclusionP.cocos extract ameliorates hyperlipidemia and lipid accumulation by regulating cholesterol homeostasis in hepatocytes through PPARα pathway. This study provides evidence that supplementation with P.cocos extract could be a potential strategy for the treatment of hyperlipidemia.