Qureshi Asaf A, Khan Dilshad A, Mahjabeen Wajiha, Papasian Christopher J, Qureshi Nilofer
Department of Basic Medical Science, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.
J Clin Exp Cardiolog. 2013 Mar 2;4(3). doi: 10.4172/2155-9880.1000238.
Age-associated altered redox imbalances and dysregulated immune function, contribute to the development of a variety of age associated diseases. Inflammatory markers and lipid profiles are useful prognostic indicators of a variety of age-associated and cardiovascular diseases. We have previously studied the impact of several proteasome inhibitors on several markers of inflammation and lipid profiles , in cell lines, animal models, and in human subjects. The current study represents an extension of this work. Our main hypothesis is that a combination of various naturally-occurring proteasome inhibitors, which inhibits nitric oxide (NO), and C-reactive protein (CRP) mediated inflammation, will have better efficacy in the prevention and treatment of age-associated disorders including cardiovascular disease.
Two double blind, randomized, placebo-controlled cross-over trials were conducted to determine the impact of a mixture of NS-5 (resveratrol, pterostilbene, quercetin, δ-tocotrienol, nicotinic acid) on serum NO, CRP, γ-glutamyl-transferase (γ-GT) activity, total antioxidant status (TAS), total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides levels. Healthy seniors (Group-1; = 32) free-living (A, B; 16/group), and hypercholesterolemic (Group-2; = 64) subjects on AHA-Step-1-diet were divided into two groups (C, D; 32/group). Baseline levels were established for parameters as mentioned above. Groups A, C were administered 4-capsules/d of NS-5 and groups B, D, placebo (starch) for 6-weeks. Groups were crossed-over, followed by a 2-week wash-out period. Groups A, C were given 4-capsules/d of placebo and groups B, D, 4-capsules/d of NS-5 for 6-weeks. Groups C, D were continued on AHA-Step-1-diet.
All the subjects completed each phase in both studies without any complaints. There were significant ( < 0.01 - 0.05) decreases in the serum levels of NO (30%, 26%), CRP (29%, 21%), γ-GT activity (14%, 17%), and blood pressure (systolic/diastolic, 3/6%, 3/3%) of Groups A and B, respectively, of free-living healthy seniors without affecting the total, HDL-, LDL-cholesterol or triglycerides compared to their respective baseline values. However, serum levels of NO (36%, 43%), CRP (31%, 48%), γ-GT (17%, 20%), total cholesterol (19%, 15%), LDL-cholesterol (28%, 20%), triglycerides (11%, 18%) of Groups C and D were significantly ( < 0.01-0.05) decreased with NS-5 treatment of hypercholesterolemic subjects compared to baseline values, without affecting the serum HDL-cholesterol levels. The serum levels of total antioxidant status (TAS) were increased (10%, 14%; < 0.05) in Groups A and B, increased (19%, 24%; < 0.02), and blood pressure (systolic/diastolic, 5/6%, 3/5%) in Groups C and D with NS-5 treatment, compared to respective baseline values.
The consumption of NS-5 mixture decreased significantly serum NO, CRP and γ-GT levels, improved TAS and lipid profiles at risk cardiovascular and hold promise for delaying onset of age-associated diseases.
与年龄相关的氧化还原失衡改变和免疫功能失调，促成了多种与年龄相关疾病的发生。炎症标志物和血脂谱是多种与年龄相关疾病和心血管疾病的有用预后指标。我们之前在细胞系、动物模型和人类受试者中研究了几种蛋白酶体抑制剂对炎症和血脂谱的多种标志物的影响。当前研究是这项工作的扩展。我们的主要假设是，多种天然存在的蛋白酶体抑制剂的组合，可抑制一氧化氮（NO）和C反应蛋白（CRP）介导的炎症，在预防和治疗包括心血管疾病在内的与年龄相关的疾病方面将具有更好的疗效。
进行了两项双盲、随机、安慰剂对照的交叉试验，以确定NS - 5（白藜芦醇、紫檀芪、槲皮素、δ - 生育三烯酚、烟酸）混合物对血清NO、CRP、γ - 谷氨酰转移酶（γ - GT）活性、总抗氧化状态（TAS）、总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和甘油三酯水平的影响。健康老年人（第1组；n = 32）自由生活（A、B组；每组16人），以及接受美国心脏协会第一步饮食的高胆固醇血症患者（第2组；n = 64）被分为两组（C、D组；每组32人）。建立上述参数的基线水平。A、C组每天服用4粒NS - 5胶囊，B、D组服用安慰剂（淀粉），持续6周。两组进行交叉，随后有2周的洗脱期。A、C组每天服用4粒安慰剂，B、D组每天服用4粒NS - 5胶囊，持续6周。C、D组继续接受美国心脏协会第一步饮食。
所有受试者均完成了两项研究的每个阶段，且无任何不适主诉。自由生活的健康老年人A组和B组的血清NO水平（分别降低30%、26%）、CRP水平（分别降低29%、21%）、γ - GT活性（分别降低14%、17%）和血压（收缩压/舒张压，分别降低3/6%、3/3%）显著（P < 0.01 - 0.05）下降，与各自的基线值相比，未影响总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇或甘油三酯水平。然而，高胆固醇血症患者C组和D组经NS - 5治疗后，血清NO水平（分别降低36%、43%）、CRP水平（分别降低31%、48%）、γ - GT（分别降低17%、20%）、总胆固醇（分别降低19%、15%）、低密度脂蛋白胆固醇（分别降低28%、20%）、甘油三酯（分别降低11%、18%）与基线值相比显著（P < 0.01 - 0.05）下降，未影响血清高密度脂蛋白胆固醇水平。与各自的基线值相比，NS - 5治疗后A组和B组的总抗氧化状态（TAS）血清水平升高（分别升高10%、14%；P < 0.05），C组和D组的血压（收缩压/舒张压，分别升高5/6%、3/5%）升高（分别升高19%、24%；P < 0.02）。
食用NS - 5混合物可显著降低血清NO、CRP和γ - GT水平，改善处于心血管疾病风险中的TAS和血脂谱，并有望延缓与年龄相关疾病的发病。
