Reduced Lipid Levels Research Articles

Effects of traditional Chinese exercise on vascular function in patients with Alzheimer's disease: A protocol for systematic review and network meta-analysis of randomized controlled trials.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an insidious onset, usually characterized by memory impairment, visual-spatial skill impairment, executive dysfunction and personality behavioral changes. Studies have confirmed that vascular dysfunction may precede AD pathological changes and can present as vascular malformations, atherosclerosis, and impaired self-regulation, and can affect oxidative stress and amyloidosis. Therefore, it is important to improve or prevent vascular dysfunction in AD patients. Regular exercise can effectively inhibit the production of reactive oxygen species during the occurrence of AD and can improve the reduction of cerebral blood flow due to AD. Previous studies have shown that exercise can achieve superior clinical results in improving vascular function in AD patients. Therefore, we hypothesize that traditional Chinese exercises (TCEs) may have a good clinical effect in improving vascular function in patients with AD. We will search "PubMed," "the Cochrane Library," "Embase," "Web of Science," "CINAHL," "ProQuest Dissertations and Theses," and "ProQuest-Health & Medical Collection," "CNKI," "SinoMed," "VIP," and "Wanfang Data" to find randomized controlled trials of the effects of TCEs on AD vascular function from the creation of the database to the present, including at least 1 indicator in carotid intima-media thickness (cIMT), middle cerebral artery mean flow velocity (MFV), blood indicators [Heme Oxidase-1 (HO-1), angiopoietin I (Ang I), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, matrix metalloproteinase-9 (MMP-9)], and arterial stiffness [(Ankle Brachial Index (ABI), pulse wave velocity (PWV)]. For the included literature, Excel 2019 will be used for data extraction and collection. For the indicators that can be netted for network meta-analysis, Surface Under the Cumulative Ranking for each exercise modality will be calculated with the help of Stata 16.0 and rank, where the higher the SUCRA score, the higher the ranking. For the indicators that cannot be netted, Review Manager 5.4 will be used for meta-analysis will be performed to evaluate the improvement effect of TCEs on AD patients. This meta-analysis will further determine the efficacy and safety of TCEs on vascular function in AD patients. In this study, randomized controlled trials of the effects of TCEs on vascular function in AD patients will be selected to provide evidence-based medical evidence for promoting the application of TCEs by observing the order of advantages and disadvantages of various exercise modalities through network meta-analysis.

Biosynthesized magnesium oxide nanoparticles from Tamarindus indica seed attenuate doxorubicin-induced cardiotoxicity by regulating biochemical indexes and linked genes

The phytochemicals of Tamarindus indica seed hydroalcoholic extract were exploited as a biocatalyst for the sustainable synthesis of magnesium oxide nanoparticles (MgO-NPs). This research investigated the cardioprotective effects of biosynthesized magnesium oxide nanoparticle (MgO-NPs). The biosynthesized seed MgO-NPs were characterized by ultraviolet-visible spectroscopy (UV–Vis), X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy-dispersive X-ray diffraction (EDX), and Fourier-transform infrared spectroscopy (FT-IR). These methodological approaches demonstrated their capacity to synthesize crystalline and aggregated MgO-NPs with a size average of 13.38 ± 0.16 nm. The biogenic MgO-NPs were found to have a significant quantity of total phenolic contents (TPC) and total flavonoid contents (TFC), indicating the existence of phenol and flavonoid-like components. The biogenic MgO-NPs demonstrated a significant free radical scavenging effects compared to different standards as measured by the inhibition of free radicals produced in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS•+), and Nitric oxide (NO) scavenging methods; they also exhibited higher ferric ion reducing capacity in FRAP assay. Moreover, they were found to be non-toxic in cytotoxic assessment. Pretreatment of Wistar Albino rats with seed MgO-NPs resulted in a significant reduction of cardiac biomarkers, i.e., cardiac Troponin-I (cTnI), creatine kinase (CK-MB), and aspartate aminotransferase (AST). The seed MgO-NPs were more successful in reducing lipid levels. The results of the mRNA expression analysis showed that seed MgO-NPs efficiently reduced the expression of the apoptotic genes p53 and Caspase-3 while restoring the expected levels of SOD gene expression. The histopathological observations were primarily focused on the disruption of cardiac fibers and myofibrillar disintegration, which are consistent with the biochemical findings. Therefore, our research suggests that MgO-NPs derived from the seeds of Tamarindus indica as a powerful antioxidant; the administration may be effective in protecting the heart from DOX-induced cardiotoxicity.

The dysregulation of plasma miR-497/FGF23 axis, and its association with clinical characteristics and major adverse cardiovascular event in female premature acute coronary syndrome patients.

MicroRNA-497 (miR-497) directly targets fibroblast growth factor 23 (FGF23) to participate in the pathology of acute coronary syndrome (ACS) by regulating atherosclerosis, inflammatory response, lipid metabolism, etc. This study intended to investigate the dysregulation of the miR-497/FGF23 axis, and its association with the major adverse cardiovascular event (MACE) in female premature ACS. MiR-497 and FGF23 from plasma samples were detected by RT-qPCR and ELISA in 979 newly diagnosed female premature ACS patients and 100 healthy controls (HCs). MACE was recorded during follow-up (median: 27.0, range: 1.0-54.0months) in female premature ACS patients. MiR-497/FGF23 axis was reduced in female premature ACS patients versus HCs [median (interquartile range): 0.7 (0.1-1.2) versus 1.9 (1.1-3.4)] (P < 0.001). Meanwhile, miR-497 negatively correlated with FGF23 in femal e premature ACS patients (P < 0.001), but not in HCs (P = 0.157). In female premature ACS patients, the miR-497/FGF23 axis was negatively associated with serum creatinine (P < 0.001), serum uric acid (P = 0.003), high-sensitivity C-reactive protein (P < 0.001), total cholesterol (P = 0.031), and low-density lipoprotein cholesterol (P = 0.003). The 1-year, 2-year, 3-year, and 4-year accumulating MACE rate was 2.9%, 8.6%, 16.7%, and 26.0%, respectively. Interestingly, a high level of miR-497/FGF23 axis predicted decreased accumulating MACE risk (P < 0.001). After adjustment by multivariate Cox's regression analysis, the high miR-497/FGF23 axis (hazard ratio (HR) = 0.005, P = 0.001) independently correlated with reduced accumulating MACE risk. The plasma miR-497/FGF23 axis represents favorable kidney function, decreased inflammation, and reduced lipid level; meanwhile, this axis possesses prognostic value in predicting decreased accumulating MACE risk in female premature ACS patients.

Analysis of the mechanism of action of quercetin in the treatment of hyperlipidemia based on metabolomics and intestinal flora.

Hyperlipidemia (HLP) is one of the main factors leading to cardiovascular diseases. Quercetin (QUE) is a naturally occurring polyhydroxy flavonoid compound that has a wide range of pharmacological effects. However, the potential mechanism for treating HLP remains unclear. Thus, the study aimed to investigate the role of QUE in HLP development and its underlying mechanisms in HLP rats based on the analysis of gut microbiota and plasma metabolomics. Following the establishment of an HLP model in rats, QUE was orally administered. Plasma samples and fecal samples were collected from HLP rats for microbiome 16S rDNA sequencing and metabolic UPLC-Q-Exactive-MS analysis. The results suggested that QUE could regulate dyslipidemia and inhibit the levels of TC, TG, and LDL-c. Additionally, histopathological findings revealed that QUE could reduce lipid deposition, ameliorate hepatic injury and steatosis in HFD-induced rats, and have a protective effect on the liver. The analysis and identification of plasma metabolomics showed that the intervention effect of QUE on HLP rats was related to 60 differential metabolites and signal pathways such as lactosamine, 11b-hydroxyprogesterone, arachidonic acid, glycerophospholipid, sphingolipid, glycerolipid, and linoleic acid metabolism. Combined with fecal microbiological analysis, it was found that QUE could significantly change the composition of intestinal flora in HLP rats, increase beneficial bacteria, and reduce the composition of harmful bacteria, attenuating the Firmicutes/Bacteroidetes ratio. The results of correlation analysis showed that the relative abundance level of Firmicutes, Deironobacterium, Fusobacterium, Bacteroides, and Escherichia coli was closely related to the change of differential metabolites. In summary, combined with metabolomics and gut microbiota studies, it is found that QUE can reduce lipid levels and improve liver function. The potential mechanism may be the regulation of metabolism and intestinal flora that play a role in reducing lipid levels, to achieve the purpose of treatment of HLP.

Effectiveness of cinnamon in the reduction of lipid levels in people with diabetes: a randomized clinical trial

RESUMO Objetivo: Avaliar a efetividade da canela na redução dos níveis lipídicos em pessoas com diabetes. Método: Ensaio clínico aleatorizado de grupos paralelos, triplo cego, realizado em Unidades Básicas de Saúde do estado do Piauí em 2019. Foram incluídas pessoas com Diabetes Mellitus tipo 2, entre 18 e 80 anos, em uso de antidiabéticos orais, e divididos em dois grupos. No grupo experimental testou-se 3g de canela por 90 dias. Resultados: 140 pessoas participaram do estudo. Destas, o grupo experimental (n= 71) apresentou redução na média dos níveis de colesterol total (p= 0,316 | IC 95% -24,9-8,1), LDL (p= 0,024 | IC 95% -29,3-2,1) e triglicerídeos (p= 0,969 | IC 95% -28,6-27,5), e aumento do HDL (p= 0,001 | IC95% 4,2-10,2). Conclusão: O uso de 3g de canela por dia, durante 90 dias, parece auxiliar na diminuição dos valores de LDL e aumento dos níveis de HDL em pacientes com diabetes.

Synergistic effect of polysaccharides and flavonoids on lipid and gut microbiota in hyperlipidemic rats.

Hyperlipidemia is a global health risk factor, and its development is closely related to the absorption and metabolism of lipids in the intestine. In this study, the Auricularia auricula polysaccharide, the Tremella polysaccharide, and hawthorn flavonoids were mixed by equal weight (HDC), and then its effect on the intervention in the intestine and blood lipids of hyperlipidemic rats on a high-fat diet (HFD) was investigated. The results revealed that HDC significantly inhibited the development of hyperlipidemia and reduced lipid levels and fat accumulation. In addition, HDC improved the edema deformation of intestinal epithelial cells, impaired the intestinal barrier induced by HFD, and improved the antioxidant capacity of the intestine. HDC showed a significant synergistic effect. Analysis of the gut microbiota by 16s rRNA gene sequencing showed that HDC reduced the ratio of Bacteroidetes/Firmicutes and the relative abundance of actinomycetes. At the genus level, the relative abundance of Lactobacillus, Rumincococcaceae-UCG-14, and Muribaculaceae was increased and the relative abundance of Allobaculum, Corynebacterium-1, Blautia, and Turicibucter was decreased. Intestinal lipidomics showed that HDC reduced the levels of DGDG, LPE, PG, phSM, PIP2, SoG1, and SM in the intestine of HFD rats, although there were no significant differences in LPE, PG, and phSM. 42 HDC-acting lipid biomarkers were screened. In conclusion, these findings support the potential of HDC intervention to prevent hyperlipidemia by regulating gut microbiota and lipid absorption and metabolism in the intestine.

Effectiveness of cinnamon in the reduction of lipid levels in people with diabetes: a randomized clinical trial.

To evaluate the effectiveness of cinnamon in reducing lipid levels in people with diabetes. Randomized clinical trial of parallel groups, triple-blind, conducted in Basic Health Units in the state of Piauí in 2019. People with Type 2 Diabetes Mellitus, between 18 and 80 years old, using oral antidiabetics, were included, and divided into two groups. The experimental group tested 3g of cinnamon for 90 days. 140 people participated in the study. From these, the experimental group (n= 71) showed a reduction in mean levels of total cholesterol (p= 0.316 | CI 95% -24.9-8.1), LDL (p= 0.024 | CI 95% -29.3 -2.1) and triglycerides (p= 0.969 | 95% CI -28.6-27.5), and increased HDL (p= 0.001 | 95% CI 4.2-10.2). The use of 3g of cinnamon per day, for 90 days, seems to help reduce LDL values and increase HDL levels in patients with diabetes.

Bisphenol S Impairs Behaviors through Disturbing Endoplasmic Reticulum Function and Reducing Lipid Levels in the Brain of Zebrafish.

The number of neurotoxic pollutants is increasing, but their mechanism of action is unclear. Here, zebrafish were exposed to 0, 1, 10, and 100 μg/L bisphenol S (BPS) for different durations beginning at 2 h postfertilization (hpf) to explore the neurotoxic mechanisms of BPS. Zebrafish larvae exposed to BPS displayed abnormal neurobehaviors. At 48 and 120 hpf, BPS inhibited yolk lipid consumption and reduced the lipid distribution in the zebrafish brain. Moreover, BPS downregulated the mRNA levels of genes involved in fatty acid elongation in the endoplasmic reticulum (ER) and activated ER stress pathways at 48 and 120 hpf, and KEGG analysis after RNA-seq showed that the protein processing pathway in the ER was significantly enriched after BPS exposure. Exposure to ER toxicants (thapsigargin and tunicamycin), two positive controls, induced neurotoxic effects on zebrafish embryos and larvae similar to those of BPS exposure. These data suggested that BPS and ER toxicants disturbed ER function and reduced brain lipid levels. Continued exposure to BPS into adulthood not only inhibited brain fatty acid elongation and ER function but also caused abnormal swelling of the ER in zebrafish. Our data provide new insights into the neurotoxic mechanism of BPS.

Rutaecarpin reduces lipids by DGKθ-dependent activation of PPARα.

Lipid metabolic disorders pose a serious threat to human health, and currently no good treatments exist. In earlier studies by the authors, HepG2 cells with diacylglycerol kinase theta (DGKθ) knockout were found to cause significant lipid accumulation, suggesting that DGKθ may be a potential target for treating lipid metabolic disorders. A high-throughput screeningof natural products targeting the potential signaling pathway of lipid metabolism was carried out in the DGKθ-T2A-luciferase knock-in HepG2 cell. RNA-sequencingand bioinformatic approaches were used to analyze the potential pathway by which rutaecarpin decreases lipids. Western blot and quantitative polymerase chain reactionwere performed to investigate the mechanisms of rutaecarpin's reduction in lipid levels. Rutaecarpin was found to significantly enhance DGKθ expression, and the potential mechanisms by which rutaecarpin accelerates lipid metabolism by targeting DGKθ was explored in vitro and in vivo. The results indicated that rutaecarpin could markedly reduce lipid accumulation in oleic acid-induced HepG2 cells and in high-fat diet-induced obese C57BL/6J mice by targeting the hepatocyte nuclear factor 1-beta (HNF1B)-DGKθ-peroxisome proliferator-activated receptor alpha (PPARα)-apolipoprotein C3 (APOC3) pathway. Rutaecarpin is effective in reducing lipid accumulation, and the development of a high-throughput screening platform based on a reporter knock-in cell line may facilitate the discovery of effective drugs for lipid metabolic disorders based on the DGKθ target.

Abstract 14703: Short Term Safety and Efficacy of Escalating Doses of Atorvastatin for Dyslipidemia in Children With Predialysis Chronic Kidney Disease Stage 2-5

Introduction: Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on safety and efficacy of statins in pediatric CKD is limited. Methods: Patients with CKD stage 2-5, aged 5- 18 years with low density lipoprotein cholesterol (LDL-C) &gt;130mg/dL and/or non-high density lipoprotein cholesterol (non HDL-C) &gt;145mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10 mg/day, and escalated to 20 mg/day if LDL-C&gt;100 mg/dL and/or non-HDL &gt;120mg/dL at 12 weeks. Proportion of patients achieving target lipid levels (LDL-C ≤100 mg/dL and non HDL-C ≤120mg/dL), change in lipid and adverse effects were assessed at 24 weeks. Wilcoxon sign rank test was used to assess percentage change in lipid. Results: Of the 31 patients enrolled, target lipid levels were achieved in 45.2% patients (95% CI 27.8%-63.7%) at 24-week; 22 patients required dose escalation to 20 mg at 12 weeks. There was no difference in median reduction in lipid levels with 10 mg/day (n=9) versus 20 mg/day (n=22; p=0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00 to 1.11) and older age (OR 36.50 95% CI 2.57 to 519.14) were independent predictors of failure to achieve target lipid levels with 10 mg/day atorvastatin. None had persistent rise in AST/ALT &gt;3 times upper normal limit (UNL) or CPK &gt;10 times UNL. No differences were noted in the adverse effects of atorvastatin 10 mg/day and 20 mg/day. Conclusions: Atorvastatin (10-20 mg/day) administered for 24 weeks was safe and effectively reduced LDL-C and non HDL-C in children with CKD stage 2-5. Patients with higher baseline LDL-C required higher doses to achieve the target.

Effect of Shuddha Guggulu on Metabolic Syndrome - A Case Report

Metabolic syndrome is conglomeration of symptoms composed of impaired fasting glucose, abdominal obesity, hypertension and dyslipidemia. It is associated with cardio metabolic risk factors with increased risk of multiple chronic diseases, including cancer and cardiovascular disease because of the increased amount of visceral fat together with a chronic inflammatory state.&#x0D; Metabolic Syndrome is resulted by the causative factors which are Santarpanakaraka in nature leading to Medodushti, which in turn leads to Medoroga. The Santarpana karaka Nidanas include the food articles that are rich in Snigdhamsha, Madhura rasa, Guru and Pichchila gunas. By consuming the food rich in such qualities produces the Rasa dhatu which is excessively composed of the qualities like Ati Snehamsha and Madhuratara Guna which produces excess Medo dhatu and causes Sthoulya. Ama present in the Medodhatu leads to further Medo dushti and manifests Metabolic Syndrome.&#x0D; Shuddha Guggulu is potent Ama pachaka dravya and does Pachana of the circulating Atisnigdha Ama in the form of lipoproteins. And also Guggulu having Lekhaneeya Guna reduces deposition of Medo dhatu and prevents inflammatory process by its anti- inflammatory potential. Aim: To assess the effect of Shuddha Guggulu in Metabolic Syndrome, dyslipidaemia. Methodology: Oral administration of the preparation in the patient. Result: There was marked improvement in signs, symptoms and biochemical parameters after intervention. Conclusion: Shuddha Guggulu is significantly effective in reducing lipid levels and CRP

Correlation between early changes of serum lipids and clinical severity in patients with wasp stings

Wasp stings are a serious problem worldwide, and patients in severe cases may experience multi-organ failure. However, the mechanism of hypolipidemia in patients with wasp stings is unknown. To investigate the relationship between early changes in lipid levels and clinical severity and the possible underlying mechanisms. A retrospective analysis of 212 patients (mild: 77; moderate: 50; severe: 85) with wasp stings was conducted. Clinical data, including lipid test results within 24 h of admission, were analysed. A total of 1060 healthy age- and gender-matched controls were used. Patients with wasp stings had lower lipid levels than healthy controls (P<0.01). Lipid levels decreased with disease severity, except for triglycerides (P<0.05). The number of stings, degree of organ failure, need for mechanical ventilation and extracorporeal blood purification, and mortality were higher in the severe group than in the mild and moderate groups (P<0.01). A decrease in lipid levels was accompanied by an increase in inflammatory indicators. In the severe group, a reduction in lipid levels was associated with ventilator application and blood purification, independent of survival status. Patients with wasp stings experience a reduction in lipid levels, which is related to the severity of clinical manifestations. Early lipid levels may serve as a simple indicator for the severity of wasp stings, and targeting lipid metabolism may be a novel treatment.

Co-crystals of ezetimibe: design, formulation and evaluation

Crystallization is a very promising approach to design solid-state properties with desired physicochemical properties. The objective of the present research work was to design, formulate and evaluate Ezetimibe cocrystals. In the present study, Cocrystals of Biopharmaceutics Classification System (BCS) Class II drug, Ezetimibe using 3-pyridine carboxamide as coformer were prepared. 3-pyridine carboxamide was selected as suitable coformer from initial screening. Cocrystals of Ezetimibe with 3-pyridine carboxamide were obtained in 1:1 ratio by solution crystallization method. Hot stage microscopy indicated interaction among drug and coformer. Differential scanning calorimetry spectra of formulated cocrystals reflected shift in endotherm corresponding to melting point in comparison to Ezetimibe, coformer and physical mixture. Fourier transform infrared (FTIR) spectra indicated towards shifting in specific bands characteristic of Ezetimibe. X-Ray Powder Diffraction pattern pointed towards crystallinity and difference in 2θ values of characteristic peaks. The cocrystals showed faster dissolution rate in comparison to Ezetimibe and marketed sample. Pharmacodynamic investigation reveals that cocrystals reduced lipid levels in serum in comparison to pure drug. Pharmaceutical Cocrystals of Ezetimibe with 3-pyridine carboxamide represented a promising approach to improve bioavailability of Ezetimibe drug.

Ameliorating mechanism of nuciferine on high-fat diet-induced dyslipidemia and hepatic steatosis by regulating intestinal absorption and serum extracellular vesicles in rats

We investigated the effects of nuciferine rich in Lotus leaf on the amelioration of hepatic steatosis and dyslipidemia of hyperlipidemic rats, and explored the underlying mechanism on miRNAs and genes expression. Serum extracellular vesicles (EVs) from rats were prepared and characterized, and interactions between miRNAs and target mRNAs were validated in 293T cell line with the double luciferase reporter gene assay. Results showed that nuciferine significantly induced the expression of PPARα, ABCA1, CYP7A1, LXRα in liver and ABCG5 in intestine, while NPC1L1 expression was markedly reduced. In vitro, double luciferase reporter assays showed that miRNA-764-5p, miRNA-758-3p, and miRNA-126-5p interacted with the target mRNAs of PPARα, ABCA1, and CYP7A1, respectively. And the effect of nuciferine on lipid metabolism in rats was related to regulate intestinal absorption and serum EVs miRNAs. These miRNAs were able to reduce lipid levels by targeting lipid metabolism genes and up-regulating PPARα-LXRα-ABCA1 pathway and CYP7A1 expression.

Puerarin attenuates hepatic steatosis via G-protein-coupled estrogen receptor-mediated calcium and SIRT1 signaling pathways.

Puerarin, the major bioactive ingredient isolated from the root of Pueraria lobata (Willd.), attenuates body weight gain and reduces lipid levels in high-fat diet-induced obese mice; however, the underlying mechanism responsible for regulating lipid metabolism remains unclear. This study investigated the molecular mechanism(s) underlying the role of puerarin in regulating lipogenesis and lipolysis in human HepG2 cells. In this study, puerarin strongly inhibited the expression of fatty acid synthase (FASN) and sterol regulatory element binding protein 1c (SREBP-1c). Moreover, puerarin significantly induced the expression of adipose triglyceride lipase (ATGL), which is responsible for triacylglycerol hydrolase activity in cells. Puerarin enhanced 5' AMP-activated protein kinase (AMPK) activity, which is a central regulator of hepatic lipid metabolism. Furthermore, this AMPK activation could be mediated by sirtuin 1 (SIRT1) and calcium signaling pathways involved in G protein-coupled estrogen receptor (GPER) signaling. GPER blockage significantly reversed the effect of puerarin on lipid accumulation and the related signaling pathways. Docking studies showed that puerarin could bind in the GPER in a similar manner as GPER agonist G1. Our results suggest that puerarin can improve hepatic steatosis by activating GPER; it's signaling cascade sequentially induced calcium and SIRT1 signaling pathways. Thus, puerarin may be a potential therapeutic agent for the treatment of non-alcoholic fatty liver disease.

The Cholesterol-Modulating Effect of the New Herbal Medicinal Recipe from Yellow Vine (Coscinium fenestratum (Goetgh.)), Ginger (Zingiber officinale Roscoe.), and Safflower (Carthamus tinctorius L.) on Suppressing PCSK9 Expression to Upregulate LDLR Expression in HepG2 Cells.

PCSK9 is a promising target for developing novel cholesterol-lowering drugs. We developed a recipe that combined molecular docking, GC-MS/MS, and real-time PCR to identify potential PCSK9 inhibitors for herb ratio determination. Three herbs, Carthamus tinctorius, Coscinium fenestratum, and Zingiber officinale, were used in this study. This work aimed to evaluate cholesterol-lowering through a PCSK9 inhibitory mechanism of these three herbs for defining a suitable ratio. Chemical constituents were identified using GC-MS/MS. The PCSK9 inhibitory potential of the compounds was determined using molecular docking, real-time PCR, and Oil red O staining. It has been shown that most of the active compounds of C. fenestratum and Z. officinale inhibit PCSK9 when extracted with water, and C. fenestratum has been shown to yield tetraacetyl-d-xylonic nitrile (27.92%) and inositol, 1-deoxy-(24.89%). These compounds could inhibit PCSK9 through the binding of 6 and 5 hydrogen bonds, respectively, while the active compound in Z. officinale is 2-Formyl-9-[.beta.-d-ribofuranosyl] hypoxanthine (4.37%) inhibits PCSK9 by forming 8 hydrogen bonds. These results suggest that a recipe comprising three parts C. fenestratum, two parts Z. officinale, and one part C. tinctorius is a suitable herbal ratio for reducing lipid levels in the bloodstream through a PCSK9 inhibitory mechanism.

Epigallocatechin-3-Gallate (EGCG) as a potential therapeutic against cardiovascular disease risk in mice

Objective: Research is focused on cardiovascular disease (CVD). CVD is the leading cause of death in the world and remains one of the major diseases strongly affected by diet and sedentary lifestyle. CVD is a class of diseases relates to the heart and or blood vessels that include, stroke, heart failure, hypertension, coronary artery disease, peripheral artery disease, and atherosclerosis caused partly due to dyslipidemia. The aim of this study was to determine the potential effect of epigallacatechin-3-gallate (EGCG) on blood lipid and glucose profiles in mice exposed to conditions that lead to CVD. Groups of male mice were subjected to different diet (standard fat diet, high fat diet and low-fat diet), exercise (voluntary, chronic and sedentary lifestyle) and EGCG supplementation. EGCG powder was dissolved in 4 ml of drinking water to deliver a daily dose of 30 mg/kg. Mice were anesthetized with isoflurane (Abbott, Cham, Switzerland) 2% (v/v) in a 20% O2 and 80% air mixture by inhalation in a closed container, then euthanized by manual cervical dislocation and were put on the animal's bed for a blood sample from the cardiac puncture. Blood was collected for lipid profiles and glucose analysis. The data was analyzed using a multi variate approach including one-way analysis of variance test (one-way ANOVA), Tukey –Kramer multiple comparison test and pairwise correlation analysis was used to determine the significance between control and treated groups. Results: The mice subjected to high-fat diet (Anova p-value = 0.00) and sedentary lifestyle (Anova p-value = 0.00) showed elevated levels for total cholesterol, low density lipoprotein’s cholesterol, triglycerides and glucose. EGCG supplementation in mice undergoing high fat diet and sedentary lifestyle resulted in a significant reduction in the lipid profiles and blood glucose (Anova p-value = 0.00). Our study showed that a high fat diet and a sedentary lifestyle predispose to hyperlipidemia and high blood glucose levels in mice and also proved that EGCG fed to hyperlipidemia mice reduces lipid levels in blood.

Ten years follow-up under atorvastatin therapy of patients with carotid artery stenosis: the prognostic impact of oxidised low-density lipoprotein on carotid plaque progression and restenosis.

Background: Atorvastatin reduces oxidized low-density lipoprotein (oxLDL) levels and reduces the rate of plaque progression in patients with and without prior carotid angioplasty. The aim of our study was to investigate the durability of this effect and to explore possible prognostic impact of oxLDL levels on carotid stenosis and plaque stability. Methods: 106 patients (71 males, mean age 64.82±7.26 years) were studied. They were divided into two groups. Group 1 including patients with carotid stenosis &gt;70% (n=50) who underwent carotid angioplasty prior to enrolment. Group 2 included those with &lt;70% stenosis who were treated medically and were given atorvastatin with dose adjusted to maintain LDL cholesterol &lt;100mg/dl. Anthropometrics, complete lipid profile, oxLDL and ultrasonography were performed at baseline, 1, 3, 6, 12 months and yearly thereafter for 10 years. Results: oxLDL levels significantly decreased from 53.3±10.91 mg/dl at baseline to 8.31±2.08 mg/dl at 12 months (p&lt;0.001) and remained stable until the 10th year. In group 1, restenosis (&gt;70%) was noticed in four patients, yet no further intervention was needed due to plaque morphology (echo-grade IV). In group 2, carotid stenosis was initially reduced (6th month – 4th year) and later relapsed (5th – 10th year), yet plaque morphology was recorded as type III or IV in almost all patients of group 2 (53=95%), indicating a significantly lower risk for stroke. Conclusion: Atorvastatin treatment to a target of LDL &lt;100 mg/dl in patients with carotid stenosis is associated with marked and durable reduction of lipid levels, especially oxLDL and LDL and reduction in the rate of stenosis progression, improved plaque stability and decreased stroke risk.

Investigation into the protective effects of hypaconitine and glycyrrhetinic acid against chronic heart failure of the rats

BackgroundThe present study aimed to determine the protective effects of hypaconitine (HA) and glycyrrhetinic acid (GA) against chronic heart failure (CHF) in the rats and to explore the underlying molecular mechanisms.MethodsThe CHF rat model was established by transverse-aortic constriction (TAC) operation. Transthoracic echocardiography and hematoxylin eosin (HE) staining were used to evaluate the pathophysiological and histopathological changes of CHF model. The total cholesterol (TCHO) and triglyceride (TG) levels were determined by ELISA assay. The protein expression of fibroblast growth factor 2 (FGF2), vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS) in the rat ventricular tissues was determined by immunohistochemistry. The serum metabolites were determined by LC-MS/MS assay.ResultsAfter applied the HA + GA, the cardiac tissue and structure were obviously improved, and the HA + GA treatment also significantly reduced the plasma levels of TCHO and TG in the CHF rats. The expression of FGF2 and VEGFA protein was up-regulated and the expression of eNOS protein was down-regulated in the ventricular tissues of CHF rats, which was significantly restored after HA + GA treatment. HA + GA treatment down-regulated serum isonicotinic acid, phosphatidylcholine, cardiolipin, estrogen glucuronide, and glycocholic acid, up-regulated serum sphingosine and deoxycholic acid in the CHF rats.ConclusionsIn conclusion, HA + GA showed protective effects on CHF in the rats, and the HA + GA may exert protective effects by reducing lipid levels, up-regulating the expression of FGF2 and VEGFA proteins, attenuating eNOS protein expression, and modulating metabolic pathways. However, the molecular mechanisms underlying HA + GA-mediated effects still require further examination.

Trypanosoma cruzi modulates lipid metabolism and highjacks phospholipids from the midgut of Rhodnius prolixus

Chagas disease is potentially life-threatening and caused by the protozoan parasite Trypanosoma cruzi. The parasite cannot synthesize some lipids and depends on the uptake of these lipids from its vertebrate and invertebrate hosts. To achieve this, T. cruzi may need to modify the physiology of the insect host for its own benefit. In this study, we investigated the interaction of T. cruzi (Y strain) with its insect vector Rhodnius prolixus and how it manipulates the vector lipid metabolism. We observed a physiological change in lipid flux in of infected insects. In the fat body of infected insects, triacylglycerol levels decreased by 80.6% and lipid storage droplet-1(LSD-1) mRNA levels were lower, when compared to controls. Lipid sequestration by infected midguts led to increased levels of 5′ AMP-activated protein kinase (AMPK) phosphorylation and activation in the fat body, inhibiting the synthesis of fatty acids and stimulating their oxidation. This led to reduced lipid levels in the fat body of infected insets, despite the fact that T. cruzi does not colonize this tissue. There was a 3-fold increase, in lipid uptake and synthesis in the midgut of infected insects. Finally, our results suggest that the parasite modifies the lipid flux and metabolism of its vector R. prolixus through the increase in lipid delivery from the fat body to midgut that are then scavenge by T cruzi.