scholarly journals Defining the Cholesterol Lowering Mechanism of Bergamot (Citrus bergamia) Extract in HepG2 and Caco-2 Cells

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3156
Author(s):  
Yunying Huang ◽  
Restituto Tocmo ◽  
Mirielle C. Nauman ◽  
Monica A. Haughan ◽  
Jeremy J. Johnson
Keyword(s):  
Hepg2 Cells ◽  
Southern Italy ◽  
Citrus Fruit ◽  
Fruit Extract ◽  
Cholesterol Lowering ◽  
Cholesterol Levels ◽  
Niemann Pick ◽  
Kinase Phosphorylation ◽  
Lowering Activity ◽  
Citrus Bergamia

Bergamot, a Mediterranean citrus fruit native to southern Italy, has been reported to have cholesterol-lowering properties; however, the mechanism of action is not well understood. Due to structural similarities with 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors, it has been proposed that the phenolic compounds in bergamot may also inhibit HMGCR. Statins are widely used for their cholesterol-lowering properties; however, they are not universally well tolerated, suggesting there is a need to identify novel cholesterol-lowering strategies. In the present study, we investigated bergamot fruit extract (BFE) and its principal components (neoeriocitrin, naringin, neohesperidin, melitidin, and brutieridin) for their ability to regulate cholesterol levels in HepG2 and Caco-2 cells. BFE at increasing concentrations decreased the levels of total and free cholesterol in HepG2 cells. BFE and its constituents did not directly inhibit HMGCR activity. However, BFE and neohesperidin decreased HMGCR levels in HepG2 cells, suggesting that neohesperidin and BFE may downregulate HMGCR expression. An increase in AMP-kinase phosphorylation was observed in BFE and neohesperidin-treated cells. In Caco-2 cells, brutieridin exhibited a significant reduction in cholesterol uptake and decreased the level of Niemann-Pick C1 Like 1, an important cholesterol transporter. Taken together, our data suggest that the cholesterol-lowering activity of bergamot is distinct from statins. We hypothesize that BFE and its principal constituents lower cholesterol by inhibiting cholesterol synthesis and absorption.

scholarly journals Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

2017 ◽  
Vol 13 ◽  
pp. 10-18 ◽  
Author(s):  
Keiichi Motoyama ◽  
Rena Nishiyama ◽  
Yuki Maeda ◽  
Taishi Higashi ◽  
Yoichi Ishitsuka ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
High Dose ◽  
Unesterified Cholesterol ◽  
Peanut Lectin ◽  
Cholesterol Lowering ◽  
Cholesterol Levels ◽  
Type C ◽  
Intracellular Cholesterol ◽  
Niemann Pick ◽  
Very High

Niemann–Pick type C (NPC) disease, characterized by intracellular accumulation of unesterified cholesterol and other lipids owing to defects in two proteins NPC1 and NPC2, causes neurodegeneration and other fatal neurovisceral symptoms. Currently, treatment of NPC involves the use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD is effective in the treatment of hepatosplenomegaly in NPC disease, albeit at a very high dose. One of the methods to reduce the required dose of HP-β-CD for treatment of NPC is to actively targeting hepatocytes with β-cyclodextrin (β-CD). The aim of the present study was to synthesize a novel multi-lactose-appended β-CD (multi-Lac-β-CD) and to evaluate its cholesterol-lowering effect in U18666A-treated HepG2 (NPC-like HepG2) cells. Further, the study aimed at delivering β-CD to hepatocytes via cholesterol-accumulated HepG2 cells, and indicated that the newly synthesized multi-Lac-β-CD had an average degree of substitution of lactose (DSL) of 5.6. This newly synthesized multi-Lac-β-CD was found to significantly decrease the concentration of intracellular cholesterol with negligible cytotoxicity as compared to HP-β-CD. An increased internalization of TRITC-multi-Lac-β-CD (DSL 5.6) as compared to TRITC-HP-β-CD was observed in NPC-like HepG2 cells. Further, the dissociation constant of peanut lectin with multi-Lac-β-CD (DSL5.6) was found to be extremely low (2.5 × 10−8 M). These results indicate that multi-Lac-β-CD (DSL5.6) diminished intracellular cholesterol levels in NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis.

scholarly journals Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols

2015 ◽  
Vol 18 (4) ◽  
pp. 344 ◽  
Author(s):  
Dhiaa A Taha ◽  
Ellen K Wasan ◽  
Kishor M Wasan ◽  
Pavel Gershkovich
Keyword(s):  
Ascorbic Acid ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Plasma Cholesterol ◽  
Plant Sterols ◽  
Water Soluble ◽  
Lipid Lowering ◽  
Cholesterol Lowering ◽  
Cholesterol Levels ◽  
Lowering Activity

Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

2015 ◽  
Vol 11 ◽  
pp. 2079-2086 ◽  
Author(s):  
Keiichi Motoyama ◽  
Yumi Hirai ◽  
Rena Nishiyama ◽  
Yuki Maeda ◽  
Taishi Higashi ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Cholesterol Content ◽  
High Dose ◽  
Dependent Manner ◽  
Lysosomal Storage ◽  
Concentration Dependent Manner ◽  
Cholesterol Lowering ◽  
Type C ◽  
Intracellular Cholesterol ◽  
Niemann Pick

The Niemann–Pick type C disease (NPC) is one of inherited lysosomal storage disorders, emerges the accumulation of unesterified cholesterol in endolysosomes. Currently, 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) has been applied for the treatment of NPC. HP-β-CyD improved hepatosplenomegaly in NPC patients, however, a high dose of HP-β-CyD was necessary. Therefore, the decrease in dose by actively targeted-β-CyD to hepatocytes is expected. In the present study, to deliver β-CyD selectively to hepatocytes, we newly fabricated mono-lactose-appended β-CyD (Lac-β-CyD) and evaluated its cholesterol lowering effects in NPC-like HepG2 cells, cholesterol accumulated HepG2 cells induced by treatment with U18666A. Lac-β-CyD (degree of substitution of lactose (DSL) 1) significantly decreased the intracellular cholesterol content in a concentration-dependent manner. TRITC-Lac-β-CyD was associated with NPC-like HepG2 cells higher than TRITC-β-CyD. In addition, TRITC-Lac-β-CyD was partially localized with endolysosomes after endocytosis. Thus, Lac-β-CyD entered NPC-like HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis and decreased the accumulation of intracellular cholesterol in NPC-like HepG2 cells. These results suggest that Lac-β-CyD may have the potential as a drug for the treatment of hepatosplenomegaly in NPC disease.

scholarly journals Activity Test of Suji Leaf Extract (Dracaena angustifolia Roxb.) on in vitro cholesterol lowering

2018 ◽  
Vol 21 (2) ◽  
pp. 54-58 ◽  
Author(s):  
Devina Ingrid Anggraini ◽  
Lily Fathrah Nabillah
Keyword(s):  
Leaf Extract ◽  
Ethanol Extract ◽  
The Body ◽  
Flavonoid Content ◽  
Cholesterol Lowering ◽  
Cholesterol Levels ◽  
Method Of Extraction ◽  
Lowering Activity ◽  
Solvent Analysis

Cholesterol is a natural substance with physical characteristic similar to fat but has a steroidal group. The body requires cholesterol in normal amount; however, it will harm the body in excess amount. High cholesterol levels in the blood are dangerous because of the precipitation of cholesterol and other fatty substances resulting in atherosclerosis. Suji leaf (Dracaena angustifolia Roxb.) used as a natural dye has a high flavonoid content that is inferred to have cholesterol-lowering activity. This study aims to test the in vitro activity of suji leaf (Dracaena angustifolia Roxb.) extract in decreasing cholesterol level with various concentrations and to find the effective concentration (EC50). The method of extraction used was remaceration method with 70% ethanol solvent. Analysis of cholesterol-lowering activity was done by Lieberman-Burchard method by making variation of ethanol extract 400 ppm, 500 ppm, 600 ppm, 700 ppm, and 800 ppm. The results showed the percentage of cholesterol-lowering activity by 33.62%, 36.15%, 46.61%, 56.39% and 64.05% respectively. Value of EC50 activity of suji leaf extract is 632.50 ppm.

scholarly journals Screening for Cholesterol-Lowering Probiotics from Lactic Acid Bacteria Isolated from Corn Silage Based on Three Hypothesized Pathways

2019 ◽  
Vol 20 (9) ◽  
pp. 2073 ◽  
Author(s):  
Changlu Ma ◽  
Shuwen Zhang ◽  
Jing Lu ◽  
Cai Zhang ◽  
Xiaoyang Pang ◽  
...  
Keyword(s):  
Bile Salt ◽  
Down Regulation ◽  
Cholesterol Removal ◽  
Cholesterol Lowering ◽  
Probiotic Potential ◽  
Cholesterol Levels ◽  
Bile Salt Deconjugation ◽  
Lowering Activity

A total of 85 strains of lactic acid bacteria were isolated from corn silage in this study and analyzed in vitro for their cholesterol removal, NPC1L1 protein down-regulation and bile salt deconjugation ability, respectively. Nineteen strains were selected for further analysis for their probiotic potential. Finally, 3 strains showing better probiotic potential were evaluated for their cholesterol-lowering activity in hamsters. The strains showing the greater cholesterol removal and NPC1L1 protein down-regulation activity had no significant effects on serum and hepatic cholesterol levels in hamsters (p > 0.05). However, Lactobacillus plantarum CAAS 18008 (1 × 109 CFU/d) showing the greater bile salt deconjugation ability significantly reduced serum low-density lipoprotein cholesterol, total cholesterol, and hepatic total cholesterol levels by 28.8%, 21.7%, and 30.9%, respectively (p < 0.05). The cholesterol-lowering mechanism was attributed to its bile salt hydrolase activity, which enhanced daily fecal bile acid excretion levels and thereby accelerated new bile acid synthesis from cholesterol in liver. This study demonstrated that the strains showing greater cholesterol removal and NPC1L1 protein down-regulation activity in vitro hardly reveal cholesterol-lowering activity in vivo, whereas the strains showing greater bile salt deconjugation ability in vitro has large potential to decrease serum cholesterol levels in vivo.

Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?

2021 ◽  
pp. 107424842110236
Author(s):  
Ruihai Zhou ◽  
George A. Stouffer ◽  
Sidney C. Smith
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Outcomes ◽  
Mechanism Of Action ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Lowering ◽  
Cholesterol Levels

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.

Sign in / Sign up

Export Citation Format

Share Document