NS-5 Resveratrol Quercetin d-Tocotrienol   # Cytokines‡ Pre-dose Post-dose Post-dose Post-dose Post-dose¶ Functions       % % % %   I Cardiovascular disease: 1 Resistin 100 86 ± 1.6** 91 ± 1.7* 88 ± 2.1* 93 ± 2.7* Regulatory role in insulin resistance, diabetes, atherosclerosis. 2 IL-2 100 89 ± 1.8* 94 ± 2.2* 89 ± 4.2* 92 ± 2.9* For growth, proliferation, & differentiation of T cells. 3 IL-6 100 63 ± 1.8** 69 ± 2.4** 85 ± 1.3** 78 ± 1.3** Cytokine regulates immune response, hematopoiesis & inflammation. 4 IL-8 100 75 ± 2.4** 80 ± 1.4** 79 ± 2.4** 75 ± 3.0** Chemokine produced by macrophages, epithelial cells, &angiogenic factor. 5 IL-12 100 73 ± 2.4** 80 ± 1.2** 92 ± 1.3* 76 ± 0.9** Plays a role in the activities of natural killer cells & T lymphocytes. 6 1L-17a 100 69 ± 2.1** 72 ± 2.1** 62 ± 0.8** 72 ± 1.5** Pro-inflammatory cytokine produced by activated T cells. 7 IL-18 100 70 ± 3.4** 83 ± 1.1** 82 ± 2.3** 76±1.3** It acts as an angiogenic factor in many diseases. 8 COX-2 100 73 ± 2.5** 82 ± 2.8** 81 ± 5.6** 70 ± 1.5** It is an enzyme, which is responsible for the production of prostanoids. 9 GAPDH 100 85 ± 7.8* 65 ± 3.3** 71 ± 4.3** 74 ± 1.7** Plays a role in glycolysis & new host defense mechanism against HIV. 10 IP-10 100 80 ± 1.1** 93 ± 0.9** 84 ± 0.7** 84 ± 2.7** It acts as potent inhibitors of angiogenesis in vivo. II Inflammation 11 TNF-a 100 75 ± 1.7** 85 ± 2.4** 81 ± 1.8** 86 ± 2.6** Cytokine produced by macrophages/monocytes during inflammation. 12 INF-g 100 75 ± 1.7** 93 ± 1.9* 80 ± 3.1** 82 ± 2.5** Potent mediators of host defense and homoeostasis. 13 MIP-1a 100 82 ± 2.1** 93 ± 0.7* 85 ± 2.2** 90 ± 2.3* Chemokines that exhibit a variety of pro-inflammatory activities. 14 NOS-2 100 72 ± 2.8** 75 ± 1.7** 71 ± 1.2** 75 ± 1.9** It is involved significantly in many vascular functions. 15 VCAM-1 100 51 ± 2.7** 64 ± 4.1** 60 ± 2.4** 60 ± 3.1** It is involved in inflammatory-linkage. 16 MCP-1 100 71 ± 3.8** 82 ± 3.3* 73 ± 2.8** 79 ± 3.3* It is a chemokine III Cancer             17 IGF-1 100 79 ± 2.7** 90 ± 1.5* 79 ± 1.2** 79 ± 1.1** It is a potent mitogen. 18 P-53 100 135 ± 2.2** 126 ± 4.1** 120 ± 5.1** 150 ± 2.9** It regulates the cell-cycle & acts as a tumor suppressor. 19 FAS-1 100 145 ± 4.0** 140 ± 4.5** 141 ± 1.9** 164 ± 4.9** It forms death-inducing signaling complex (DISC) upon ligand binding 20 VEGF 100 79 ± 2.4** 79 ±4.0** 82 ± 4.1** 78 ± 2.4** Role in stabilizing the endothelial cell adhesion & signal transduction. 21 CCND-1 100 65 ± 2.7** 69 ± 1.6** 68±3.8** 68±1.3** Controls progression of cells by activating cyclin-dependent kinase. IV Diabetes 22 PAI-1 100 82±1.3** 86±4.6** 59 ±3.1** 84±1.2* Involved in atherosclerosis & diabetes. V Aging             23 IL-1a 100 60 ±1.3** 68±3.5** 82±1.5** 75±3.2** It is an agonist mediating inflammatory and immuno-modulatory effects. 24 IL-10 100 34±1.7** 69±3.0** 52±3.7** 65±1.2** Pleiotropic effects in immuno-regulation and 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. ‡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 3: Effects of NS-5, resveratrol, quercetin, and  δ-tocotrienol (Pre-dose vs Post-dose) on plasma cytokines/proteins in hypercholesterolemic humans.