scholarly journals Anticholesterolemic Activity of Three Vegetal Extracts (Artichoke, Caigua, and Fenugreek) and Their Unique Blend

2021 ◽  
Vol 12 ◽  
Author(s):  
Jessica Frigerio ◽  
Erik Tedesco ◽  
Federico Benetti ◽  
Violetta Insolia ◽  
Giovanna Nicotra ◽  
...  
Keyword(s):  
Bile Acids ◽  
Free Cholesterol ◽  
Complementary Therapies ◽  
Liver Lipid ◽  
Plaque Formation ◽  
Hepatic Cell ◽  
Monacolin K ◽  
Atherosclerotic Plaque Formation ◽  
The Impact

Hepatic-related diseases, in particular hyperlipidemia and hypercholesterolemia, are a thorn on the side of the national health institutes around the globe. Indeed, liver lipid and cholesterol dysregulation could lead to atherosclerotic plaque formation and cardiovascular diseases. Currently, statin administration and monacolin K consumption are the main therapies proposed to counter this alarming connection, but relevant side effects are known. To overcome this issue, safe nutraceutical formulations and/or vegetal extracts, endowed with anticholesterolemic activity, could be instrumental in hypercholesterolemia prevention and treatment. In the present work, the anticholesterolemic efficacy of three vegetal extracts used in traditional medicine (artichoke, caigua, and fenugreek), their unique blend (ACFB), and the monacolin K-containing red yeast extract (RYR), was investigated with an in vitro approach based on hepatic cell line HepG2. The impact on cholesterol of the three extracts, their blend, and RYR were investigated by determining hepatocyte total and free cholesterol and bile acids biosynthesis. According to our results, the anticholesterolemic activity of the vegetal extracts was confirmed, and a novel choleretic activity of caigua extract was evidenced. ACFB showed to be safer than RYR while showing a similar effect on total and free cholesterol and bile acids synthesis compared to it. The anticholesterolemic activity of the blend was obtained with lower vegetal extract concentrations compared with the single vegetal extract, potentially indicating an additive effect between the extracts. In conclusion, the vegetal extracts and their blend, ACFB, are safe and are endowed with anticholesterolemic activity, potentially providing complementary therapies to the statin-based ones for hyperlipidemia and hypercholesterolemia-related complications.

scholarly journals Evaluating Hepatobiliary Transport with 18F-Labeled Bile Acids: The Effect of Radiolabel Position and Bile Acid Structure on Radiosynthesis and In Vitro and In Vivo Performance

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Stef De Lombaerde ◽  
Ken Kersemans ◽  
Sara Neyt ◽  
Jeroen Verhoeven ◽  
Christian Vanhove ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Membrane Vesicles ◽  
Hepatic Uptake ◽  
Hepatobiliary Transport ◽  
Bile Acid Transporters ◽  
Significant Difference ◽  
The Impact

Introduction. An in vivo determination of bile acid hepatobiliary transport efficiency can be of use in liver disease and preclinical drug development. Given the increased interest in bile acid Positron Emission Tomography- (PET-) imaging, a further understanding of the impact of 18-fluorine substitution on bile acid handling in vitro and in vivo can be of significance. Methods. A number of bile acid analogues were conceived for nucleophilic substitution with [18F]fluoride: cholic acid analogues of which the 3-, 7-, or 12-OH function is substituted with a fluorine atom (3α-[18F]FCA; 7β-[18F]FCA; 12β-[18F]FCA); a glycocholic and chenodeoxycholic acid analogue, substituted on the 3-position (3β-[18F]FGCA and 3β-[18F]FCDCA, resp.). Uptake by the bile acid transporters NTCP and OATP1B1 was evaluated with competition assays in transfected CHO and HEK cell lines and efflux by BSEP in membrane vesicles. PET-scans with the tracers were performed in wild-type mice (n=3 per group): hepatobiliary transport was monitored and compared to a reference tracer, namely, 3β-[18F]FCA. Results. Compounds 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA were synthesized in moderate radiochemical yields (4–10% n.d.c.) and high radiochemical purity (>99%); 7β-[18F]FCA and 12β-[18F]FCA could not be synthesized and included further in this study. In vitro evaluation showed that 3α-FCA, 3β-FGCA, and 3β-FCDCA all had a low micromolar Ki-value for NTCP, OATP1B1, and BSEP. In vivo, 3α-[18F]FCA, 3β-[18F]FGCA, and 3β-[18F]FCDCA displayed hepatobiliary transport with varying efficiency. A slight yet significant difference in uptake and efflux rate was noticed between the 3α-[18F]FCA and 3β-[18F]FCA epimers. Conjugation of 3β-[18F]FCA with glycine had no significant effect in vivo. Compound 3β-[18F]FCDCA showed a significantly slower hepatic uptake and efflux towards gallbladder and intestines. Conclusion. A set of 18F labeled bile acids was synthesized that are substrates of the bile acid transporters in vitro and in vivo and can serve as PET-biomarkers for hepatobiliary transport of bile acids.

Abstract 444: Semaphorin3A Reduces Atherosclerotic Plaque Formation in ApoE Knock Out Mice Through Regulation of M2 Type Macrophage Migration

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Talin Ebrahimian ◽  
Maryam Heidari ◽  
David Simon ◽  
Hojatollah Vali ◽  
Craig A Mandato ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Inflammatory Diseases ◽  
Plaque Formation ◽  
Atherosclerotic Plaques ◽  
M2 Macrophages ◽  
Aortic Sinus ◽  
Knock Out ◽  
Atherosclerotic Plaque Formation ◽  
Beta 1 Integrin

Objective: Recent data point to an important immunomodulatory role for neural guidance molecules, including semaphorin 3a (Sema-3A), in inflammatory diseases. Sema-3A is a secreted member of the Sema family and is produced by several immune cells including macrophages. We found that Sema-3A receptors are expressed in macrophages and in atherosclerotic plaques. Approach and results: To investigate the role of Sema-3A in atherosclerosis, ApoE-/- mice were administered with a Sema-3A overexpressing or a control plasmid and were fed a high fat diet for 9 weeks. Sema-3A receptors were expressed in macrophages and atherosclerotic plaques. Our results show that Sema-3A overexpressing mice had significantly smaller atherosclerotic plaques than control mice in the aortic sinus (0.3±0.02 vs. 0.4±0.03 mm 2 ), the brachiocephalic artery (0.04±0.01 vs. 0.1±0.01 mm 2 ) and the aorta (9.5±1.4 vs 15.3±2.9%), assessed by oil red O staining. No differences were observed in plaque stability, measured by collagen and smooth muscle cell alpha-actin staining. However, there was significantly less (2-fold) macrophage content in the plaques of Sema-3A compared to control mice, associated with decreased circulating monocytes determined by flow cytometry as cd11b positive and Gr-1 negative cells (4.97±0.74 vs. 7.2±0.62%). To better define the involved mechanisms, we investigated macrophage function In vitro and found that recombinant Sema-3A increased by 4 fold migration of M2 but not M1 macrophages. In addition, active beta-1 integrin expression was significantly enhanced (2-fold) by Sema-3A in human M2 macrophages. Importantly, Sema-3A induced a significant increase (by 50%) of focal adhesion kinase phosphorylation. Conclusions: Our data show that Sema-3A prevents atherosclerotic plaque formation in ApoE -/- mice. This may be due in part to enhanced motility and function of M2 macrophages through regulation of beta-1 integrin.

scholarly journals Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation

2021 ◽  
Author(s):  
Carina Mauersberger ◽  
Hendrik B Sager ◽  
Jana Wobst ◽  
Tan An Dang ◽  
Laura Lambrecht ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Guanylyl Cyclase ◽  
Leukocyte Adhesion ◽  
Vascular Inflammation ◽  
Soluble Guanylyl Cyclase ◽  
Plaque Formation ◽  
Allele Carrier ◽  
Atherosclerotic Plaque Formation ◽  
Angiopoietin 1

Aim: The role of platelets in atherosclerosis remains incompletely understood. Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here we sought to investigate the contribution of platelet sGC to atherosclerosis and the therapeutic potential of targeting sGC in atherosclerosis. Methods and Results: We genetically deleted sGC in platelets of atherosclerosis-prone Ldlr-/- mice. By intravital fluorescence microscopy such Pf4-Cre+Gucy1b1flox/floxLdlr-/- mice displayed enhanced leukocyte adhesion to atherosclerotic plaques in comparison with their litter mates. Moreover, histological and flow cytometry analyses revealed more numerous inflammatory leukocytes and larger plaque sizes in aortic tissue of Ldlr-/- mice lacking sGC in platelets. In vitro, supernatant from activated platelets lacking sGC promoted leukocyte adhesion to endothelial cells (EC) via enhanced EC activation. Using cytokine profiling, we identified reduced angiopoietin-1 release by Pf4-Cre+Gucy1b1flox/flox and human GUCY1A1 risk allele carrier platelets to be responsible for enhanced activation of EC and subsequent leukocyte adhesion. Pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced recruitment of adoptively transferred leukocytes in Ldlr-/- mice fed a Western diet. Pharmacological sGC stimulation further reduced atherosclerotic plaque formation and vascular inflammation. Conclusion: Loss of sGC in platelets contributes to atherosclerotic plaque formation via reduced release of the soluble factor angiopoietin-1 and, subsequently, enhanced leukocyte recruitment. Pharmacological sGC stimulation might represent a novel therapeutic strategy to prevent and treat CAD.

CHRONIC ORAL DEFIBROTIDE STIMULATES VASCULAR PGI2 AND INHIBITS ATHEROSCLEROTIC PLAQUE FORMATION IN CHOLESTEROL-FED RABBITS

1987 ◽  
Author(s):  
P Lobel ◽  
M Palmer ◽  
K Schor
Keyword(s):  
Elevated Serum ◽  
Atp Release ◽  
Rabbit Aorta ◽  
Plaque Formation ◽  
Atherosclerotic Plaque Formation ◽  
Subjective Score ◽  
Standard Laboratory Diet ◽  
Elevated Serum Cholesterol ◽  
Fold Stimulation

Defibrotide (DEF) is a polydeoxyribonucleotide fraction from bovine lung, possessing profibrinolytic and PGI2 stimulating properties. Male rabbits were fed for 4 months a standard laboratory diet (150 g/day) without (A) or with (B) DEF or a cholesterol (1%) supplemented diet without (C) or with (D) DEF (60 mg/kg x day) was administered orally (drinking water) and withdrawn 24-36 h prior to the acute experiments.DEF did not change the elevated serum cholesterol: 18 ± 2 (C) vs. 26 ± 5 (D) mM but significantly reduced the plaque formation in the aorta from 4.5 ± 0.3 (C) to 3.3 ± 0.2 (D) (subjective score). Collagen induced (0.6 pg/ml) thromboxane formation and ATP release was significantly reduced by DEF: 55+2 (C) vs. 42 ± 2 (D) ng/ml TXB2; 152 ± 11 (C) vs. 74±5 (D) AU ATP (platelet rTch plasma). DEF significantly increased the basal and bradykinin (Bk, 30 nM) stimulated PGI2 release from rabbit aorta preparations in Krebs buffer, while the PGI2 forming capacity (arachidonic acid, AA, 30 pg/ml) was unchanged Furthermore, the iloprost (30 nM) stimulated cAMP was significantly elevated by DEF in both control: 115 ± 10 (A) vs. 155 ± 18 (B) pmoles/1 and cholesterol-fed rabbits: 120 ± 14 (C) vs. 172 ± 9 (D). DEF, directly added to the platelets in vitro did not inhibit platelet activation up to 100 pg/ml.The data demonstrate a 2-3-fold stimulation of basal and hormone (Bk) induced PGI2 formation of control and sclerotic rabbit aorta after 4 months DEF treatment while the atherosclerosis per se does not significantly change these parameters. DEF treatment also significantly reduces platelet hyperreactivity at unchanged serum ch() lesterol. Both properties might be useful to prevent complication’s of atherosclerosis, such as myocardial infarction and stroke.

scholarly journals Murine roseolovirus does not accelerate amyloid-β pathology and human roseoloviruses are not over-represented in Alzheimer disease brains

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Tarin M. Bigley ◽  
Monica Xiong ◽  
Muhammad Ali ◽  
Yun Chen ◽  
Chao Wang ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Rna Sequencing ◽  
Amyloid Β ◽  
Plaque Formation ◽  
In Vivo Studies ◽  
Sequencing Analysis ◽  
The Impact

Abstract Background The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-β (Aβ) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Aβ deposition. Methods We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD. Results We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Aβ interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Aβ plaque formation. Moreover, −omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD. Conclusion Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Aβ plaque formation and AD.

scholarly journals Hepatic lipid droplets. Isolation, morphology and composition

1973 ◽  
Vol 132 (2) ◽  
pp. 323-327 ◽  
Author(s):  
Richard P. DiAugustine ◽  
Joan-Marie Schaefer ◽  
James R. Fouts
Keyword(s):  
Fatty Acids ◽  
Electron Micrographs ◽  
Lipid Droplets ◽  
Free Cholesterol ◽  
Hepatic Cell ◽  
Cholesterol Esters ◽  
Lipid Layer ◽  
Outer Coat ◽  
Mean Diameter

The floating lipid layer isolated centrifugation of rat liver was examined for composition and ultrastructure. It was chiefly composed of triglycerides and cholesterol esters plus much smaller amounts of free cholesterol, diglycerides, phospholipid and protein. No free fatty acids were detected. The triglyceride and cholesterol ester fractions consisted mostly of esters of linoleic acid, oleic acid and palmitic acid. Electron micrographs of the floating lipid layer revealed numerous spherical osmiophilic droplets having a mean diameter of 0.5–2μm with a very-thin dense outer coat. Similar structures were observed as organelles in electron micrographs of the intact liver cell. The amount of triglyceride in the layer decreased in rats starved for 72h, but pellet triglyceride (homogenate minus the floating lipid layer) was unchanged. These results suggest that the floating lipid layer is the representative in vitro of lipid-rich organelles which probably function as a depot form of hepatic-cell neutral lipid.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

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