Loffredo L, Baratta F, Ludovica P, Battaglia S, Carnevale R, Nocella C, Novo M, Pannitteri G, Ceci F, Angelico F, Violi F, Del Ben M
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
Department of Internal Medicine and Medical Specialties, I Clinica Medica, Sapienza University of Rome, Rome, Italy.
Nutr Metab Cardiovasc Dis. 2017 Nov 13;28(2):143-149. doi: 10.1016/j.numecd.2017.10.027.
Oxidative stress plays a pivotal role in inducing endothelial dysfunction and progression from simple fatty liver steatosis (FLD) to non-alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide-phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess endothelial function and oxidative stress in a population affected by simple FLD and NASH. Furthermore, we analysed the effect of high vs low content of cocoa polyphenols on endothelial function and oxidative stress in patients with NASH.
In a cross-sectional study we analysed endothelial function, as assessed by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2 activation, serum isoprostanes and nitric oxide bioavailability (NOx), in patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we performed a randomized, cross-over study in 19 subjects with NASH comparing the effect of 14-days administration of 40 g of chocolate at high (dark chocolate, cocoa >85%) versus low content (milk chocolate, cocoa <35%) of polyphenols on FMD and oxidative stress. Compared to controls, NASH and FLD patients had higher Nox2 activity and isoprostanes levels and lower FMD and NOx, with a significant gradient between FLD and NASH. The interventional study showed that, compared to baseline, FMD and NOx increased (from 2.9 ± 2.4 to 7.2 ± 3.0% p < 0.001 and from 15.9 ± 3.6 to 20.6 ± 4.9 μM, p < 0.001, respectively) in subjects given dark but not in those given milk chocolate. A simple linear regression analysis showed that Δ (expressed by difference of values between before and after 14 days of chocolate assumption) of FMD was associated with Δ of Nox2 activity (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs: 0.557; p < 0.001).
Cocoa polyphenols improve endothelial function via Nox2 down-regulation in NASH patients.
氧化应激在诱导内皮功能障碍以及促使单纯性脂肪肝（FLD）进展为非酒精性脂肪性肝炎（NASH）的过程中起关键作用。多酚类物质可通过抑制烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶亚型Nox2来减轻氧化应激并恢复内皮功能。本研究旨在评估受单纯性FLD和NASH影响人群的内皮功能和氧化应激。此外，我们分析了高含量与低含量可可多酚对NASH患者内皮功能和氧化应激的影响。
在一项横断面研究中，我们分析了NASH患者（n = 19）、FLD患者（n = 19）和对照组（n = 19）的内皮功能（通过血流介导的血管舒张功能（FMD）评估）以及氧化应激（通过Nox2激活、血清异前列腺素和一氧化氮生物利用度（NOx）评估）。然后，我们对19名NASH受试者进行了一项随机交叉研究，比较给予40克高含量（黑巧克力，可可含量>85%）与低含量（牛奶巧克力，可可含量<35%）多酚巧克力14天对FMD和氧化应激的影响。与对照组相比，NASH和FLD患者的Nox2活性和异前列腺素水平更高，FMD和NOx更低，且FLD和NASH之间存在显著梯度。干预研究表明，与基线相比，给予黑巧克力的受试者FMD和NOx增加（分别从2.9±2.4增加到7.2±3.0%，p<0.001；从15.9±3.6增加到20.6±4.9μM，p<0.001），而给予牛奶巧克力的受试者则没有。简单线性回归分析表明，FMD的变化量（以摄入巧克力14天前后的值的差值表示）与Nox2活性的变化量（Rs = -0.323；p = 0.04）、血清异前列腺素（Rs：-0.553；p<0.001）和NOx（Rs：0.557；p<0.001）相关。
可可多酚通过下调NASH患者的Nox2来改善内皮功能。
