Fahey Jed W, Kensler Thomas W
Department of Medicine, Division of Clinical Pharmacology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, United States.
Front Nutr. 2021 Apr 29;8:648788. doi: 10.3389/fnut.2021.648788. eCollection 2021.
Broccoli sprouts are a convenient and rich source of the glucosinolate glucoraphanin, which can generate the chemopreventive agent sulforaphane through the catalytic actions of plant myrosinase or β-thioglucosidases in the gut microflora. Sulforaphane, in turn, is an inducer of cytoprotective enzymes through activation of Nrf2 signaling, and a potent inhibitor of carcinogenesis in multiple murine models. Sulforaphane is also protective in models of diabetes, neurodegenerative disease, and other inflammatory processes, likely reflecting additional actions of Nrf2 and interactions with other signaling pathways. Translating this efficacy into the design and implementation of clinical chemoprevention trials, especially food-based trials, faces numerous challenges including the selection of the source, placebo, and dose as well as standardization of the formulation of the intervention material. Unlike in animals, purified sulforaphane has had very limited use in clinical studies. We have conducted a series of clinical studies and randomized clinical trials to evaluate the effects of composition (glucoraphanin-rich [± myrosinase] vs. sulforaphane-rich or mixture beverages), formulation (beverage vs. tablet) and dose, on the efficacy of these broccoli sprout-based preparations to evaluate safety, pharmacokinetics, pharmacodynamic action, and clinical benefit. While the challenges for the evaluation of broccoli sprouts in clinical trials are themselves formidable, further hurdles must be overcome to bring this science to public health action.
西兰花芽是硫代葡萄糖苷萝卜硫苷的便捷且丰富的来源，萝卜硫苷可通过植物黑芥子酶或肠道微生物群中的β-硫代葡萄糖苷酶的催化作用生成化学预防剂萝卜硫素。反过来，萝卜硫素是一种通过激活Nrf2信号传导来诱导细胞保护酶的物质，并且在多种小鼠模型中是一种有效的致癌作用抑制剂。萝卜硫素在糖尿病、神经退行性疾病和其他炎症过程的模型中也具有保护作用，这可能反映了Nrf2的其他作用以及与其他信号通路的相互作用。将这种功效转化为临床化学预防试验，尤其是基于食物的试验的设计和实施，面临着诸多挑战，包括来源、安慰剂和剂量的选择以及干预材料配方的标准化。与动物不同，纯化的萝卜硫素在临床研究中的应用非常有限。我们进行了一系列临床研究和随机临床试验，以评估成分（富含萝卜硫苷[±黑芥子酶]与富含萝卜硫素或混合饮料）、配方（饮料与片剂）和剂量对这些基于西兰花芽的制剂的功效、安全性、药代动力学、药效学作用和临床益处的影响。虽然在临床试验中评估西兰花芽本身面临着巨大挑战，但要将这一科学转化为公共卫生行动，还必须克服更多障碍。
