Lowering of cholesterol bioaccessibility and serum concentrations by saponins: in vitro and in vivo studies

2015 ◽  
Vol 6 (2) ◽  
pp. 501-512 ◽  
Author(s):  
Liliya Vinarova ◽  
Zahari Vinarov ◽  
Vasil Atanasov ◽  
Ivayla Pantcheva ◽  
Slavka Tcholakova ◽  
...  

Quillaja saponariaandSapindus trifoliatusextracts decrease cholesterol bioaccessibility duringin vitrodigestion and lower serum cholesterol in mice.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ana Asenjo-Bueno ◽  
Elena Alcalde-Estevez ◽  
Patricia Sosa ◽  
Patricia Plaza ◽  
Lucia Serrano-Garcia ◽  
...  

Abstract Background and Aims Patients with chronic kidney disease (CKD) present a high rate of cardiovascular mortality mainly associated with endothelial dysfunction, which causes more cardiovascular events in presence of atherosclerosis. Atherosclerosis is characterized by a significant increase of low density lipoproteins (LDL), reactive oxygen species (ROS) and inflammation. ROS can oxidize LDL generating oxidized-LDL (oxLDL) that promotes the development of cardiovascular pathologies. The aim of this study was to evaluate whether oxLDL induce endothelial dysfunction analysing the involvement of vascular fibrosis. Method The model used for in vivo studies was the Knockout apolipoprotein E (KO-apoE) mice, which resemble human atherosclerosis and shown high levels of cholesterol (LDL) that can be oxidized to oxLDL. In mice, blood pressure was registered before sacrificed them. After that, we measured different parameters as serum cholesterol levels, vascular function by vascular reactivity in mesenteric arteries and vascular fibrosis in aorta by Sirius Red staining and by the protein expression of fibronectin and collagen-I by immunohistochemistry. In order to investigate the mechanism of action of oxLDL, in vitro studios were performed on human smooth muscle cells (SMC) incubated with oxLDL at different times. Fibrosis was evaluated by the expression of TGF- β and extracellular matrix proteins such as fibronectin and collagen-I by Western blot and by immunofluorescence. ROS production was also measured by fluorescence confocal microscopy, using the CellROX Deep Red probe. Results KO-apoE mice shown higher levels of serum cholesterol and blood pressure than WT animals. Moreover, KO-apoE mice showed endothelial dysfunction since their arteries were less relaxed and more contracted. In addition, these mice presented thickening of vascular wall (SMC layer), more fibrosis showing intense Sirius Red staining and less expression of elastin, all compatible with their vascular dysfunction compared to WT mice. Furthermore, aortas from KO-apoE mice showed a slight increase in fibronectin and collagen-I expression assessed by immunohistochemistry. In vivo studies were confirmed in vitro after treating SMC with oxLDL. oxLDL induced fibrosis in SMC by increasing TGF-β, fibronectin and collagen-I protein expressions evaluated by Western blot and immunofluorescence assays. Treatment with oxLDL also increased ROS production, which seem to be responsible of oxLDL-induced fibrosis in human SMC, as it was blocked in the presence of the antioxidant N-Acetyl-cysteine. Conclusion In summary, these results point to endothelial dysfunction associated to atherosclerosis (oxLDL) could be mediated by an increase in the development of vascular fibrosis where ROS could play an important role. Therefore, the endothelial dysfunction typical of CKD patients could impair with more vascular fibrosis when atherosclerosis is also present.


2001 ◽  
Vol 5 (8) ◽  
pp. 645-651
Author(s):  
M. Peeva ◽  
M. Shopova ◽  
U. Michelsen ◽  
D. Wöhrle ◽  
G. Petrov ◽  
...  
Keyword(s):  

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S198-S198
Author(s):  
Joseph R Meno ◽  
Thien-son K Nguyen ◽  
Elise M Jensen ◽  
G Alexander West ◽  
Leonid Groysman ◽  
...  

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.


2020 ◽  
Vol 72 (5) ◽  
Author(s):  
Mario Fadin ◽  
Maria C. Nicoletti ◽  
Marzia Pellizzato ◽  
Manuela Accardi ◽  
Maria G. Baietti ◽  
...  
Keyword(s):  

Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel  were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.  


Sign in / Sign up

Export Citation Format

Share Document