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British Journal of Medicine and Medical Research, ISSN: 2231-0614,Vol.: 6, Issue.: 4


Dose-dependent Modulation of Lipid Parameters, Cytokines and RNA by δ-tocotrienol in Hypercholesterolemic Subjects Restricted to AHA Step-1 Diet


Asaf A. Qureshi1*, Dilshad A. Khan 2, Wajiha Mahjabeen2 and Nilofer Qureshi1,3

1Department of Basic Medical Sciences, University of Missouri–Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.
2Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, National University of Medical Science, Rawalpindi, Pakistan.
3Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.

Article Information
(1) Sinan Ince, Department of Pharmacology and Toxicology, University of Afyon Kocatepe, Turkey.
(2) Jimmy T. Efird, Department of Public Health, Epidemiology and Outcomes Research, East Carolina Heart Institute, Brody School of Medicine, Greenville, North Carolina, USA.
(1) Anonymous, Hungary.
(2) Sahar Mohamed Kamal Shams El-Dine, Pharmacology Department, Ain Shams University, Egypt.
(3) Anonymous, India.
(4) Anonymous, USA.
(5) Anonymous, Chile.
(6) Anonymous, Finland.
(7) Anonymous, USA.
Complete Peer review History: http://www.sciencedomain.org/review-history/7349


Aims: Evaluate the consumption of δ-tocotrienol (free from tocopherols) on serum lipid parameters, and several cytokines (TNF-α, IL-4, IL-6, IL-8, IL-10), including gene expression and circulating microRNAs (miRNAs) in hypercholesterolemic subjects.
Study Design: The present preliminary dose-response study consisted of six phases. All hypercholesterolemic subjects took increasing doses of δ-tocotrienol (125, 250, 500,750 mg/d) plus AHA Step-1 diet for 4 weeks during the 30 weeks study period.
Methodology: Hypercholesterolemic (n = 31; serum cholesterol > 5.2 mmol/L) subjects (males-26/females 5; age range 50-71 years) were enrolled in the study from WahCantonment, Pakistan. Serum lipid parameters were measured by auto analyzers. Various plasma cytokines, cDNA, and miRNAs were estimated by Signosis kits.
Results: All participants (n = 31) completed all phases of study. The δ-tocotrienol plus AHA Step-1 diet caused reductions in lipid parameters in a dose-dependent manner with maximum effects on serum total cholesterol (15%), LDL-cholesterol (18%), triglycerides (14%) with 250 mg/d dose (P< 0.001). Doses above 500 mg/d resulted ininduction in levels of all lipid parameters, except HDL-cholesterol. The cytokines associated with cardiovascular disease (plasma TNF-α, IL-2, IL-4, IL-6, IL-8, IL-10) were all down-regulated 39%-64% by δ-tocotrienol treatment (P< 0.01). Similar results were obtained with gene expression of these cytokines using whole blood messenger-RNA. In contrast, circulating miRNA-7a, miRNA-15a, miRNA-20a (anti-angiogenic), miRNA-21, miRNA-29a, miRNA-92a, miRNA-200, miRNA-206 (skeletal muscle regeneration) down-regulated in hypercholesterolemic subjects, were up-regulated by δ-tocotrienol treatment as compared to baseline (P< 0.01).
Conclusions: The present results confirm that consumption of δ-tocotrienol plus AHA Step-1 diet causes significant reduction in serum lipid parameters and several cytokines (TNF-α, IL-2, IL-4, IL-6, IL-8, IL-10) at a low optimal dose (250 mg/d). The capacity of δ-tocotrienol to modulate inflammation is partly attributable to dose-dependent properties of inhibition/activation, which may play a major role in future treatment of cardiovascular diseases.

Keywords :

DeltaGold-90% δ-tocotrienol + 10% γ-tocotrienol; lipid parameters; inflammatory biomarkers; cytokines; TNF-α; gene expression; circulatory miRNAs.

Full Article - PDF    Page 351-366

DOI : 10.9734/BJMMR/2015/13820

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