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

Asaf A. Qureshi *

Department of Basic Medical Sciences, University of Missouri–Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.

Dilshad A. Khan

Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, National University of Medical Science, Rawalpindi, Pakistan.

Wajiha Mahjabeen

Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, National University of Medical Science, Rawalpindi, Pakistan.

Nilofer Qureshi

Department of Basic Medical Sciences, University of Missouri–Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA. and Division of Pharmacology and Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.

*Author to whom correspondence should be addressed.


Abstract

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


How to Cite

Qureshi, A. A., Khan, D. A., Mahjabeen, W., & Qureshi, N. (2014). Dose-dependent Modulation of Lipid Parameters, Cytokines and RNA by δ-tocotrienol in Hypercholesterolemic Subjects Restricted to AHA Step-1 Diet. Journal of Advances in Medicine and Medical Research, 6(4), 351–366. https://doi.org/10.9734/BJMMR/2015/13820

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