Marrubium vulgare extract inhibits human-LDL oxidation and enhances HDL-mediated cholesterol efflux in THP-1 macrophage

Life Sciences ◽  
2006 ◽  
Vol 80 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Hicham Berrougui ◽  
Maxim Isabelle ◽  
Mounia Cherki ◽  
Abdelouahed Khalil
2007 ◽  
Vol 85 (9) ◽  
pp. 918-927 ◽  
Author(s):  
Hicham Berrougui ◽  
Mounia Cherki ◽  
Geremy Abdull Koumbadinga ◽  
Maxim Isabelle ◽  
Jasmin Douville ◽  
...  

Prevention of lipoprotein oxidation by natural compounds may prevent atherosclerosis via reducing early atherogenesis. In this study, we investigated for the first time the beneficial properties of methanolic extract of argania pericarp (MEAP) towards atherogenesis by protecting human low-density lipoprotein (LDL) against oxidation while promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. By measuring the formation of malondialdehyde (MDA) and conjugated diene as well as the lag phase and the progression rate of lipid peroxidation, the MEAP was found to possess an inhibitory effect. In addition, MEAP reduced the rate of disappearance of α-tocopherol as well as the apoB electrophoretic mobility in a dose-dependent manner. These effects are related to the free radical scavenging and copper-chelating effects of MEAP. In terms of cell viability, MEAP has shown a cytotoxic effect (0–40 μg/mL). Incubation of3H-cholesterol-loaded J774 macrophages with HDL in the presence of increasing concentrations of MEAP enhanced HDL-mediated cholesterol efflux independently of ABCA1 receptor pathways. Our findings suggest that argania seed pericarp provides a source of natural antioxidants that inhibit LDL oxidation and enhance cholesterol efflux and thus can prevent development of cardiovascular diseases.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Debi Swertfeger ◽  
Hailong Li ◽  
Sandra Rebholz ◽  
Amy S Shah ◽  
W S Davidson ◽  
...  

HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, inhibition of oxidation, and stimulation of endothelial function. It has been proposed that various HDL sub-particles exist, each with distinct protein and lipid compositions. We hypothesized that fractionation of plasma would separate HDL particles with different protein compositions into distinct populations responsible for different HDL functions. Plasma from 10 healthy adults was fractionated by gel filtration and the protein composition of phospholipid containing fractions was analyzed by mass spectrometry. Each fraction was assessed for its ability to efflux cholesterol from macrophages, as well as its ability to inhibit LDL oxidation. Correlations were made between individual proteins in the HDL fractions and their ability to participate in both functional assays. One peak of activity was found in the cholesterol efflux assay when analyzing fractions in the HDL range. Cholesterol efflux activity did not correlate strongly with any protein in the HDL range of fractions, though there was a weak correlation with Protein S (r=0.337, p<0.01). However, the phospholipid (PL) and cholesterol (CH) concentration of the fractions correlated strongly with efflux (r=0.75. and r=0.61 respectively, both p<0.00001) across all fractions (both LDL and HDL). In contrast, the PL or CH content were not correlated with anti-oxidation activity. However, there were 2 strong peaks of anti-oxidation activity in the HDL range that did correlate with specific proteins (all values of r>0.3 and p<0.05). Activity in the first peak, fraction 25, in the small HDL range, correlated most strongly with ceruloplasmin and inter-α-trypsin inhibitor 4, while activity in the second peak, fraction 28, in the minimally lipidated/free protein range, correlated with gelsolin and albumin. In conclusion, we have shown that PL and CH correlate more strongly with cholesterol efflux than any protein in the HDL sub-fractions, while the protein composition of particular HDL sub-fractions is a better indicator of its anti-oxidative capacity than the PL or CH concentration.


2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.


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