Tocotrienols: Exciting Biological and Pharmacological Properties of Tocotrienols and Naturally Occurring Compounds, Part II.

δ-Tocotrienol plus AHA Step-1 diet in hypercholesterolemic subjects caused reductions in lipid parameters (14% to 18%) with 250 mg/d dose, and 500 mg/d resulted induction in these parameters. Although, α-tocopherol is the most bioavailable form of vitamin E. There are few reports on bioavailability of tocotrienols in humans. Pharmacokinetics and bioavailability of δ-tocotrienol was quantified on plasma levels of tocol isomers, cytokines, and microRNAs. Subjects were fed doses of 125 mg/d to 500 mg/d. Plasma samples collected between 0 h to 10 h, levels of tocols estimated by HPLC, which resulted dose-dependent increases in AUC0-10, Cmax0-∞, Tmaxh, t1/2h, Cl-T 1/h, Vd/f, keh-1. Maximum plasma levels of δ-tocotrienol were at 3 h (125 mg/d to 250 mg/d), 6 h (500 mg/d). Effects of 32 compounds were evaluated on TNF-α secretion, nitric oxide production, and gene expression (TNF-α, IL-1β, IL-6, iNOS activity) in PPAR-α knockout mice. Anticancer activities of thiostrepton, dexamethasone, 2-methoxyestradiol, δ-tocotrienol, quercetin, amiloride, quinine sulfate showed significant anti-proliferative properties in Hela cells, pancreatic, prostate, breast, lungs, melanoma, B-lymphocytes, T-cells (40% to 95%). Results of plasma total mRNAs after δ-tocotrienol feeding to hepatitis C patients revealed significant down-regulated gene expression of pro-inflammatory cytokines. A mixture of δ-tocotrienol, resveratrol, vitamin D3 (NS-3) were given two capsules/d or cellulose/olive oil as placebo to individuals with T2DM (24-weeks). Significant down-regulation (15% to 74%) of gene expression in diabetes biomarkers and decreases i n serum levels of fasting-glucose, HbA1c, hs-CRP, fasting-insulin, HOMA-IR, MDA (9% to 23%) were observed with NS-3 treated T2DM. Pure plasma mRNAs and miRNAs of pre-dose vs. post-dose of NS-3 treated samples were analyzed by Next Generation Sequencing (NGS). Venn diagrams have established genetic regulatory network images and canonical signaling pathways for mRNA, miRNA, and paired mRNA-miRNA.