NS-5 Resveratrol Quercetin d-Tocotrienol   # Cytokines‡ Pre-dose Post-dose Post-dose Post-dose Post-dose¶ Functions       % % % %   I Cardiovascular disease: 1 Resistin§ 100 71 ± 1.4** 84 ± 1.5** 88 ± 1.8** 81 ± 1.6** Regulatory role in insulin resistance, diabetes, atherosclerosis. 2 IL-2 100 67 ± 2.7** 51 ± 1.9** 65 ± 1.6** 75 ± 0.7** For growth, proliferation, & differentiation of T cells to (Effector T) cells. 3 IL-6 100 75 ± 1.2** 77 ± 1.4** 83 ± 2.4** 83 ± 1.2** Regulates the immune response, hematopoiesis and inflammation. 4 IL-8 100 68 ± 2.9** 69 ± 3.3** 77 ± 2.2* 75 ± 0.3** Produced by macrophages & epithelial cells, potent angiogenic factor. 5 IL-12 100 74 ± 2.9** 82 ± 2.8* 84 ± 2.7* 75 ± 2.9** It plays a key role in the activities of natural killer cells and T lymphocytes. 6 1L-17a 100 44 ± 3.3** 60 ± 2.4** 74 ± 3.1** 49 ± 3.4** This gene is a pro-inflammatory cytokine produced by activated T cells. 7 IL-18 100 72 ± 1.4** 85 ± 1.7** 50 ± 3.9** 85 ± 1.8* It acts as an angiogenic factor in many diseases. 8 COX-2 100 68 ± 3.2** 76 ± 1.5** 75 ± 3.6** 74 ± 2.9** It is an enzyme, which is responsible for the production of prostanoids. 9 GAPDH 100 70 ± 1.1** 73 ± 2.3** 77 ± 2.8** 80 ± 2.5** Key role in glycolysis & new host defense mechanism against HIV. 10 IP-10 100 58 ± 1.7** 83 ± 2.9* 82 ± 2.6* 57 ± 2.1** It acts as potent inhibitor of angiogenesis in vivo. II Inflammation: 11 TNF-a 100 63 ± 1.2** 71 ± 1.3* 68 ± 2.1* 42 ± 2.7* Cytokines produced by macrophages/monocytes during inflammation. 12 INF-g 100 67 ± 2.4** 75 ± 3.3** 73 ± 2.1** 67 ± 2.9** Potent mediators of host defense and homoeostasis. 13 MIP-1a 100 62 ± 1.8** 70 ± 2.3** 73 ± 3.5** 68 ± 1.9** A subfamily of chemokines that exhibit pro-inflammatory activities. 14 NOS-2 100 65 ± 1.8** 75 ± 1.5** 63 ± 3.9** 65 ± 2.4** It is involved significantly in many vascular functions. 15 VCAM-1 100 61 ± 1.7** 68 ± 2.7** 63 ± 4.1** 50 ± 3.8** It is involved in inflammatory-linkage. 16 MCP-1 100 78 ± 1.5** 87 ± 1.7** 80 ± 2.9* 75 ± 1.4** It is a chemokine. III Cancer             17 IGF-1 100 78 ± 1.1** 84 ± 2.2** 86 ± 2.7* 75 ± 3.1* It is a potent mitogen. 18 P-53 100 197 ± 4.2** 135 ± 3.2** 156 ± 3.9* 141 ± 4.1* It regulates the cell-cycle and acts as a tumor suppressor. 19 FAS-1 100 231 ± 6.7* 123 ± 3.4* 127 ± 2.1* 135 ± 3.2* It forms death-inducing signaling complex (DISC) upon ligand binding 20 VEGF 100 66 ± 2.3* 71 ± 2.4* 79 ± 3.1* 73 ± 3.6* Role in stabilizing the endothelial cell adhesion & signal transduction. 21 CCND-1 100 62 ± 1.8** 76 ± 2.3* 68 ± 3.5* 65 ± 1.5** Controls progression of cells by activating cyclin-dependent kinase. IV Diabetes 22 PAI-1 100 22 ± 2.2** 46 ± 2.3** 70 ± 1.6** 63 ± 2.8** Associated with atherosclerosis and have increased levels in diabetics. V Aging             23 IL-1a 100 57 ± 2.1** 75 ± 2.6** 76 ± 2.9** 77 ± 1.7** Agonist mediating inflammatory and immuno-modulatory effects. 24 IL-10 100 72 ± 2.6** 73 ± 4.1** 66 ± 1.5** 62 ± 1.6** Cytokine with pleiotropic effects in immuno-regulation & inflammation. * - **Values in a row sharing a common asterisk are significantly different at *P<0.01; **P<0.001. ¶The effect of δ-tocotrienol on resistin, IL-2, IL-6, IL-8, IL-10, IL-12, TNF-α and IFN-γ has been reported recently (AAQ et al. BJMMR. 6(4): 351-366, JCEC. 2015; 6:4. 1000367. ‡The cytokines IL-12, IL-17α, IL-18 (inflammation); IL-2 (cancer); and resistin, IL-6, IL-17α (diabetes) also involved in these diseases. §Resistin = Obesity-mediated insulin resistance and Type 2 diabetes Mellitus; IL-2: Interleukin-2; IL-6: Interleukin-6, 8, 12, 17α, 18; COX-2: Cyclooxygenase-2; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; TNF-α: Tumor Necrosis Factor-α; INF-γ: Interferon-γ; MIP-1α: Macrophage Inflammatory Protein-1α; NOS-2: Nitric Oxide Synthase-2; VCAM-1: Vascular Cell Adhesion Molecule-1; MCP-1: Monocyte Chemotactic Protein-1; IGF-1: Insulin-like Growth Factor-1; P-53: P-53 tumor suppressor protein; FAS-1: Fatty Acid Synthetase-1; VGEF: Vascular Endothelial Growth Factor; CCND-1: Cyclin D-1; PAI-1: Plasminogen Activator Inhibitor-1; IL-1α: Interleukin-1α; IL-10: Interleukin-10.

Table 2: Effects of NS- 5, resveratrol, quercetin, and δ-tocotrienol (Pre-dose vs Post-dose) on plasma cytokines/proteins of normal cholesterolemic humans.