Marotta Francesco, Marcellino Massimiliano, Solimene Umberto, Cuffari Biagio, Yadav Hariom, Khokhlov Alexander N, Lorenzetti Aldo, Mantello Amelie, Cervi Joseph, Catanzaro Roberto
ReGenera Research Group for Aging Intervention, San Babila Clinic, Milano, Italy.
WHO-Center for Traditional Medicine and Biotechnology, University of Milano, Italy.
Clin Pharmacol Biopharm. 2017;6. doi: 10.4172/2167-065X.1000170. Epub 2017 May 18.
In recent years a number of studies have reported the significant relationship between metabolic syndrome and neurodegenerative disease. There is accumulating evidence that the interplay of combined genetic and environmental risk factors (from diet to life style to pollutants) to intrinsic age-related oxi-inflammatory changes may be advocated for to explain the pandemic of neurodegenerative diseases. In recent years a specific Fermented Papaya Preparation (FPP) has been shown to significantly affect a number of redox signalling abnormalities in a variety of chronic diseases and as well in aging mechanisms either on experimental and on clinical ground. The aim of the present study was to evaluate FPP use in impending metabolic disease patients with potentially neurodegenerative disease clustered risk factors. The study population consisted of 90 patients aged 45-65 years old, with impending metabolic syndrome and previously selected as to be ApoE4 genotype negative. By applying a RCT, double-blind method, one group received FPP 4.5 g twice a day (the most common dosage utilized in prior clinical studies) while the other received an oral antioxidant cocktail (trans-resveratrol, selenium, vitamin E, vitamin C). Then, after 21 month treatment period, a selected heavy metal chelator was added at the dosage of 3 g/nocte for the final 3 months study treatment. The parameters tested were: routine tests oxidized LDL-cholesterol, anti-oxidised LDL, Cyclophilin-A (CyPA), plasminogen activator inhibitor-1 and CyPA gene expression. From this study it would appear that FPP, unlike the control antioxidant, significantly decreased oxidized-LDL and near normalizing the anti-Ox-LDL/Ox-LDL ratio (p<0.001) although unaffecting the lipid profile . Moreover, only FPP decreased cyclophilin-A plasma level and plasminogen activator-inhibitor (p<0.01) together with downregulating cyclophilin-A gene expression (p<0.01). Insulin resistance was only mildly improved. Heavy metals gut clearance proved to be effectively enhanced by the chelator (p<0.01) and this was not affected by any of the nutraceuticals, nor it added any further benefit to the biological action of FPP.
近年来，多项研究报告了代谢综合征与神经退行性疾病之间的显著关系。越来越多的证据表明，综合遗传和环境风险因素（从饮食到生活方式再到污染物）与内在的与年龄相关的氧化炎症变化之间的相互作用，可能有助于解释神经退行性疾病的流行。近年来，一种特定的发酵木瓜制剂（FPP）已被证明在实验和临床方面均能显著影响多种慢性疾病以及衰老机制中的一些氧化还原信号异常。本研究的目的是评估FPP在具有潜在神经退行性疾病聚集风险因素的即将发生代谢疾病患者中的应用。研究人群包括90名年龄在45至65岁之间、即将发生代谢综合征且先前被选定为ApoE4基因型阴性的患者。通过采用随机对照试验、双盲方法，一组患者每天两次服用4.5克FPP（先前临床研究中最常用的剂量），而另一组患者服用口服抗氧化剂鸡尾酒（反式白藜芦醇、硒、维生素E、维生素C）。然后，在21个月的治疗期后，在最后3个月的研究治疗中添加剂量为3克/每晚的选定重金属螯合剂。测试的参数包括：常规测试氧化型低密度脂蛋白胆固醇、抗氧化型低密度脂蛋白、亲环蛋白A（CyPA）、纤溶酶原激活物抑制剂-1以及CyPA基因表达。从这项研究来看，与对照抗氧化剂不同，FPP显著降低了氧化型低密度脂蛋白，并使抗氧化型低密度脂蛋白/氧化型低密度脂蛋白比值接近正常（p<0.001），尽管对血脂谱没有影响。此外，只有FPP降低了亲环蛋白A的血浆水平和纤溶酶原激活物抑制剂（p<0.01），同时下调了亲环蛋白A基因表达（p<0.01）。胰岛素抵抗仅得到轻微改善。螯合剂被证明有效增强了重金属的肠道清除能力（p<0.01），这不受任何营养保健品的影响，也没有给FPP的生物学作用带来任何进一步的益处。
