Guggulsterone, a farnesoid X receptor antagonist lowers plasma trimethylamine-N-oxide levels: An evidence from in vitro and in vivo studies

2018 ◽  
Vol 38 (3) ◽  
pp. 356-370 ◽  
Author(s):  
A Gautam ◽  
YN Paudel ◽  
SAZ Abidin ◽  
U Bhandari
Keyword(s):  
Hepatic Injury ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Farnesoid X Receptor ◽  
Lipoprotein Cholesterol ◽  
In Vivo Studies ◽  
Low Density Lipoprotein Cholesterol ◽  
Pro Inflammatory Cytokines

The current study investigated the role of guggulsterone (GS), a farnesoid X receptor antagonist, in the choline metabolism and its trimethylamine (TMA)/flavin monooxygenases/trimethylamine- N-oxide (TMAO) inhibiting potential in a series of in vitro and in vivo studies as determined by high-performance liquid chromatography (HPLC), mass spectroscopy (MS), and liquid chromatography (LC)-MS techniques. Atherosclerosis (AS) was successfully induced in a group of experimental animals fed with 2% choline diet for 6 weeks. Serum lipid profiles such as total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured. Pro-inflammatory cytokines levels, markers for a hepatic injury, and oxidative stress markers were assessed. Interestingly, GS reduced the level of TMA/TMAO in both in vitro and in vivo studies as demonstrated by the peaks obtained from HPLC, MS, and LC–MS. Furthermore, GS exhibited cardioprotective and antihyperlipidemic effects as evidenced by the attenuation of levels of several serum lipid profiles and different atherogenic risk predictor indexes. GS also prevented hepatic injury by successfully restoring the levels of hepatic injury biomarkers to normal. Similarly, GS inhibited the production of pro-inflammatory cytokines levels, as well as GS, enhanced antioxidant capacity, and reduced lipid peroxidation. Histopathological study of aortic sections demonstrated that GS maintained the normal architecture in AS-induced rats. On the basis of results obtained from current investigation, we suggest that GS might have a great therapeutic potential for the treatment of AS.

scholarly journals Cholesterol-Lowering Effects of Lactobacilli and Bifidobacteria Probiotics in vitro and in vivo

2018 ◽  
pp. 1-12
Author(s):  
Shahenda, M. Elaby ◽  
Asmaa A. Salem ◽  
Jehan, B. Ali ◽  
A. F. Abdel-Salam
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Lowering

Two lactobacilli strains; Lactobacillus acidophilus ATCC 20079 and Lactobacillus plantarum ATCC 20179 and two bifidobacteria strains; Bifidobacterium bifidum GSGG 5286 and Bifidobacterium longum ATCC 15707 were studied their abilities to reduce the cholesterol content in vitro. It was investigated that the in vivo cholesterol-lowering effect of L. plantarum ATCC 20179, B. bifidum GSGG 5286 and mixture of both probiotics (L. plantarum ATCC20179 and B. bifidum GSGG5286) on hyperlipidaemic rats for 8 weeks. All lactobacilli and bifidobacteria strains assimilate the cholesterol content in laboratory media. It was observed the highest assimilation of cholesterol was in L. plantarum ATCC 20179 and B. bifidum GSGG 5286 strains. In vivo, L. plantarum ATCC 20179  group was more effective in improving serum lipid profile levels [total cholesterol (TC), triglycerides (TG), low density lipoprotein – cholesterol (LDL-C), high density lipoprotein – cholesterol                   (HDL-C), very low density lipoprotein – cholesterol (VLDL-C) and Atherogenic Index (AI)],                      liver enzyme activities (ALT, AST and ALP),  malonaldehyde (MDA), hydrogen peroxide (H2O2) and total antioxidants capacity (TAC) levels than mixed-organisms and B. bifidum groups, respectively of hyperlipidaemic rats. It was concluded that L. plantarum ATCC 20179 showed more                     favourable results than B. bifidum GSGG 5286 in relation to cardiovascular risk factors in hyperlipidaemic rats.

Some metabolic characteristics of low-density lipoprotein subfractions, LDL-1 and LDL-2: in vitro and in vivo studies

1988 ◽  
Vol 960 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Dorine W. Swinkels ◽  
Pierre N.M. Demacker ◽  
Heidi L.M. Hak-Lemmers ◽  
Marc J.T.M. Mol ◽  
Sing H. Yap ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies ◽  
Low Density ◽  
Lipoprotein Subfractions ◽  
Metabolic Characteristics

In vitro and in vivo cholesterol lowering ability of Lactobacillus pentosus KF923750

2017 ◽  
Vol 8 (2) ◽  
pp. 271-280 ◽  
Author(s):  
F. Bendali ◽  
K. Kerdouche ◽  
S. Hamma-Faradji ◽  
D. Drider
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Lactobacillus Pentosus ◽  
Survival Percentage

Lactobacillus pentosus KF923750 was characterised for probiotic related properties and then characterised for cholesterol uptake in vitro as well as in vivo using rabbits fed a high-cholesterol diet. The survival percentage of L. pentosus KF923750 was 100% at pH 3, 52.18% at pH 2 and 36.21% at pH 2 plus pepsin. Similarly, this strain appeared resistant to bile (0.1% [98.42%], 0.3% [88.52%], 0.5% [75.60%] and 1% [71.15%]), after 4 h exposure. Moreover, L. pentosus KF923750 controlled growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 through the production of a bacteriocin-like inhibitory substance and anti-adhesive capabilities. L. pentosus KF923750 was non-cytotoxic to eukaryotic cells but sensitive to some antibiotics. Compared with rabbits fed a high-cholesterol diet but without L. pentosus KF923750 supplementation, the plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in L. pentosus KF923750-fed rabbits by 11.54, 16.00 and 18.00%, respectively, with no significant change in high-density lipoprotein cholesterol levels. The histological sections of livers revealed lesions in all the rabbits that were fed a high-cholesterol diet, but these were less pronounced in rabbits ingesting L. pentosus KF923750. This study highlights the potential of lactobacilli, such as L. pentosus KF923750, in the treatment or prevention of hypercholesterolemia.

scholarly journals Synthetic nanoemulsion resembling a protein-free model of 7-ketocholesterol containing low density lipoprotein: In vitro and in vivo studies

2010 ◽  
Vol 43 (4) ◽  
pp. 439-444 ◽  
Author(s):  
Giovani M Favero ◽  
Raul C Maranhão ◽  
Durvanei A Maria ◽  
Débora Levy ◽  
Sérgio P Bydlowski
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies ◽  
Low Density ◽  
Free Model

scholarly journals Novel PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) Variants in Patients With Familial Hypercholesterolemia From Cape Town

2020 ◽  
Author(s):  
Roeland Huijgen ◽  
Dirk J. Blom ◽  
Merel L. Hartgers ◽  
Kévin Chemello ◽  
Asier Benito-Vicente ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Proprotein Convertase ◽  
Low Density Lipoprotein Cholesterol ◽  
Cascade Screening ◽  
Gain Of Function

Objective: Familial hypercholesterolemia (FH) is characterized by elevated low-density lipoprotein-cholesterol and markedly increased cardiovascular risk. In patients with a genetic diagnosis, low-density lipoprotein receptor ( LDLR ) mutations account for >90% of cases, apolipoprotein B ( APOB ) mutations for ≈5% of cases, while proprotein convertase subtilisin kexin type 9 ( PCSK9 ) gain of function mutations are rare (<1% of cases). We aimed to evaluate the functional impact of several novel PCSK9 variants in a cohort of patients with FH by genetic cascade screening and in vitro functionality assays. Approach and Results: Patients with clinically diagnosed FH underwent genetic analysis of LDLR , and if negative, sequential testing of APOB and PCSK9 . We analyzed cosegregation of hypercholesterolemia with novel PCSK9 variants. Gain of function status was determined by in silico analyses and validated by in vitro functionality assays. Among 1055 persons with clinical FH, we identified nonsynonymous PCSK9 variants in 27 (2.6%) patients and 7 of these carried one of the 4 previously reported gain of function variants. In the remaining 20 patients with FH, we identified 7 novel PCSK9 variants. The G516V variant (c.1547G>T) was found in 5 index patients and cascade screening identified 15 additional carriers. Low-density lipoprotein-cholesterol levels were higher in these 15 carriers compared with the 27 noncarriers (236±73 versus 124±35 mg/dL; P< 0.001). In vitro studies demonstrated the pathogenicity of the G516V variant. Conclusions: In our study, 1.14% of cases with clinical FH were clearly attributable to pathogenic variants in PCSK9 . Pathogenicity is established beyond doubt for the G516V variant.

scholarly journals The Cholesterol-Lowering Effect of Alisol Acetates Based on HMG-CoA Reductase and Its Molecular Mechanism

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Fei Xu ◽  
Hui Yu ◽  
Cai Lu ◽  
Jun Chen ◽  
Wei Gu
Keyword(s):  
Molecular Simulation ◽  
Reductase Activity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
The Impact

This study measured the impact of alisol B 23-acetate and alisol A 24-acetate, the main active ingredients of the traditional Chinese medicine Alismatis rhizoma, on total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) levels of hyperlipidemic mice. The binding of alisol B 23-acetate and alisol A 24-acetate to the key enzyme involved in the metabolism of TC, 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, was studied using the reagent kit method and the western blotting technique combined with a molecular simulation technique. According to the results, alisol acetates significantly lower the TC, TG, and LDL-C concentrations of hyperlipidemic mice, while raising HDL-C concentrations. Alisol acetates lower HMG-CoA reductase activity in a dose-dependent fashion, both in vivo and in vitro. Neither of these alisol acetates significantly lower the protein expression of HMG-CoA. This suggests that alisol acetates lower the TC level via inhibiting the activity of HMG-CoA reductase by its prototype drug, which may exhibit an inhibition effect via directly and competitively binding to HMG-CoA. The side chain of the alisol acetate was the steering group via molecular simulation.

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