Asaf A Qureshi, Dilshad A Khan, Wajiha Mahjabeen, Neerupma Silswal and Nilofer Qureshi
Background: Inhibitory effects of NS-5 mixture of resveratrol, quercetin, δ-tocotrienol, nicotinic acid on several inflammatory and cardiovascular risk factors have been reported in normal cholesterolemic and hypercholesterolemic humans. The hypothesis was that combination of cholesterol-lowering and inflammatory-reducing properties of NS-5 mixture would be more effective than its individual components in reducing the serum levels of several biomarkers of cardiovascular disease in humans. However, effects of NS-5 mixture and its components did not report effects on cytokines, gene expression, and microRNAs were not reported in previous publication. As this area is gaining importance in the understanding of various transcriptional factors and signal pathways, which regulate several biomarkers in various diseases.
Aims: Modulation of NS-5 mixture, and its components were evaluated on superoxide production in HUVEC in vitro, and on serum levels of total cholesterol, NO, CRP, TAS, plasma cytokines, gene expression, miRNAs in vivo in normal cholesterolemic and hypercholesterolemic humans.
Study design: Study was carried out as double-blind randomized, trial of NS-5 mixture, resveratrol, quercetin, and δ-tocotrienol in free-living healthy and hypercholesterolemic humans.
Results: The NS-5 mixture, resveratrol, quercetin, δ-tocotrienol, or nicotinic acid treatments caused reduction in superoxide production (11% to 24%; P<0.01) in HUVEC. These reductions were more pronounced with LPSstimulated HUVEC (26% to 40%; P<0.01) compared to predose values. These findings were further supported by decreases (P<0.01) in serum total cholesterol levels of NS-5 treated group (24%) versus resveratrol (18%), quercetin (20%), and δ-tocotrienol (22%) in hypercholesterolemic humans, followed by reduction of NO, CRP and increases in TAS in normal cholesterolemic and hypercholesterolemic humans. There was significant (P<0.001) down-regulation in pro-inflammatory cytokines and gene expression of resistin, IL-2α, IL-6, IL-12, IL-18, TNF-α, and others, that are normally involved in pathogenesis of atherosclerosis, diabetes, and aging processes. The plasma inflammatory miRNAs (miR-101a, miR-125a, miR-155, miR-223) were down-regulated as compared to predose values. The elevated levels of miRNA-146a during senescence were down-regulated after treatment with these compounds.
Conclusions: This is the first report that describes the effects of NS-5 mixture, its components on proteomics, gene expression and levels of miRNAs in normal cholesterolemic and hypercholesterolemic humans. Results suggest that NS-5 mixture and its components are potent agents in the reduction of superoxide production, cardiovascular risk factors and inflammatory biomarkers, which are modulated by NF-κB. Maximum inhibition in superoxide production and other risk factors was observed with NS-5 mixture as compared with its individual components, thus supporting our hypothesis.