scholarly journals Rutin and Quercetin Decrease Cholesterol in HepG2 Cells but Not Plasma Cholesterol in Hamsters by Oral Administration

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3766
Author(s):  
Ning Liang ◽  
Yuk-Man Li ◽  
Zouyan He ◽  
Wangjun Hao ◽  
Yimin Zhao ◽  
...  
Keyword(s):  
Oral Administration ◽  
Hepg2 Cells ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Regulatory Element ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.

scholarly journals Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and HepG2 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Hiroe Go ◽  
Jin Ah Ryuk ◽  
Hye Won Lee ◽  
In Sil Park ◽  
Ki-Jung Kil ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Cholesterol Synthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Protein Levels ◽  
Related Disease

The present study was conducted to investigate the effect of Sagunja-tang on the lipid related disease in a rat model of menopausal hyperlipidemia and lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells. Inin vivostudy using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media thickness, and nonalcoholic steatohepatitis score, when compared to menopausal hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased the lipid accumulation, total cholesterol levels, and low-density/very-low-density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-β-cyclodextrin-induced decrease in the protein levels of critical molecule involved in cholesterol synthesis, sterol regulatory element binding protein-2, and low-density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of AMP-activated protein kinase was stimulated by Sagunja-tang. These results suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation through regulation of cholesterol synthesis and AMPK activityin vitro. These observations support the idea that Sagunja-tang is bioavailable bothin vivoandin vitroand could be developed as a preventive and therapeutic agent of hyperlipidemia in postmenopausal females.

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.

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

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 Endoplasmic Reticulum Stress Affects Lipid Metabolism in Atherosclerosis Via CHOP Activation and Over-Expression of miR-33

2018 ◽  
Vol 48 (5) ◽  
pp. 1995-2010 ◽  
Author(s):  
Yan Sun ◽  
Dai Zhang ◽  
Xiaoli Liu ◽  
Xuesong Li ◽  
Fang Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Er Stress ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder ◽  
The Relationship

Background/Aims: Endoplasmic reticulum (ER) stress is an important event in atherosclerosis. Recent studies have shown that ER stress deregulates cholesterol metabolism via multiple pathways. This study aimed to determine the relationship between ER stress and lipid metabolism and to verify that upregulation of miR-33 is involved in this process. Methods: An atherosclerosis model was established in apolipoprotein E-deficient (ApoE-/-) mice fed a Western diet, and THP-1 derived macrophages were used in this study. Hematoxylin-eosin and Oil Red O staining were used to quantify the atherosclerotic plaques. 1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate labeled oxidized low-density lipoprotein binding assay and a Cholesterol Efflux Fluorometric Assay Kit were used to observe cholesterol uptake and efflux. The mRNA and protein levels of biomarkers associated with ER stress and cholesterol metabolism in atherosclerotic plaques and macrophages were evaluated by real-time PCR and western blotting, respectively. Immunofluorescence was used to observe alterations of ABCA1 localization. Small interfering RNAs were used to knock down CHOP and miR-33 in macrophages to alter CHOP and miR-33 expression. Results: Atherosclerotic lesions and systemic lipid levels were ameliorated after inhibition of ER stress (tauroursodeoxycholic acid) in vivo. In vitro studies confirmed that ER stress regulated the lipid catabolism of macrophages by promoting cholesterol uptake, inhibiting cholesterol efflux, and modulating the expression of related transporters. CHOP contributed to lipid metabolism disorder following ER stress. Furthermore, over-expression of miR-33 was involved in ER stress that induced lipid metabolism disorder in macrophages. These findings support a model of ER stress induction by oxidized low-density lipoprotein that affects macrophage lipid catabolism disorder. Conclusion: Our data shed new light on the relationship between ER stress and lipid metabolism in vivo and in vitro, and confirm that upregulation of miR-33 is involved in this process. The relationship between ER stress and miR-33 represents a novel target for the treatment of atherosclerosis.

scholarly journals NPC1L1 Facilitates Sphingomyelin Absorption and Regulates Diet-Induced Production of VLDL/LDL-associated S1P

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2641
Author(s):  
Yoshihide Yamanashi ◽  
Tappei Takada ◽  
Hideaki Yamamoto ◽  
Hiroshi Suzuki
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
In Vivo Studies ◽  
Lipid Mediator ◽  
Low Density ◽  
Dependent Manner ◽  
Niemann Pick

Niemann-Pick C1-Like 1 (NPC1L1) is a cholesterol importer and target of ezetimibe, a cholesterol absorption inhibitor used clinically for dyslipidemia. Recent studies demonstrated that NPC1L1 regulates the intestinal absorption of several fat-soluble nutrients, in addition to cholesterol. The study was conducted to reveal new physiological roles of NPC1L1 by identifying novel dietary substrate(s). Very low-density lipoprotein and low-density lipoprotein (VLDL/LDL) are increased in Western diet (WD)-fed mice in an NPC1L1-dependent manner, so we comprehensively analyzed the NPC1L1-dependent VLDL/LDL components. Apolipoprotein M (apoM), a binding protein of sphingosine-1-phosphate (S1P: a lipid mediator), and S1P were NPC1L1-dependently increased in VLDL/LDL by WD feeding. S1P is metabolized from sphingomyelin (SM) and SM is abundant in WD, so we focused on intestinal SM absorption. In vivo studies with Npc1l1 knockout mice and in vitro studies with NPC1L1-overexpressing cells revealed that SM is a physiological substrate of NPC1L1. These results suggest a scenario in which dietary SM is absorbed by NPC1L1 in the intestine, followed by SM conversion to S1P and, after several steps, S1P is exported into the blood as the apoM-bound form in VLDL/LDL. Our findings provide insight into the functions of NPC1L1 for a better understanding of sphingolipids and S1P homeostasis.

In vitro, in vivo studies of a new amphiphilic adsorbent for the removal of low-density lipoprotein

Biomaterials ◽  
2003 ◽  
Vol 24 (13) ◽  
pp. 2189-2194 ◽  
Author(s):  
Yan Cheng ◽  
Shenqi Wang ◽  
Yaoting Yu ◽  
Yi Yuan
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
In Vivo Studies ◽  
Low Density
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