营养失调与治疗杂志

抽象的

2020 年食品峰会：浆果可预防癌症 - Gary D Stoner - 威斯康星医学院

加里·斯托纳

过去二十年，人们开展了大量研究，以评估浆果的抗癌潜力。几个世纪以来，野生浆果一直是人类饮食中不可或缺的一部分。它们的主要用途是提供营养，但有些品种也用于药用。最重要的可销售浆果种类包括越橘属（蓝莓、越橘、蔓越莓、欧洲山桑子）、悬钩子属（黑莓、红树莓、黑帽莓、云莓）、草莓属（草莓）和接骨木属（接骨木、红接骨木）。这些浆果含有大量的植物化学物质，其中许多对人类健康具有潜在重要性。植物化学物质是非营养性化合物，主要由次级代谢产生，可保护植物免受紫外线、捕食者和寄生虫的侵害，调节化学途径，并为浆果提供风味和颜色。浆果中最有趣的植物化学物质可能是多酚，它赋予浆果大部分的抗氧化潜力。多酚可分为酚酸和黄酮类化合物，前者由具有至少一个羟基的芳香环结构组成，后者是更复杂的分子。酚酸约占人类每日多酚摄入量的 30%，黄酮类化合物约占 70%。黄酮类化合物种类繁多，包括花青素、香草醇、黄酮醇、异黄酮、黄酮和黄酮。这些类别在基本化学结构上羟基的数量和分布上有所不同。Seeram 和实验室的最新评论对浆果中包括黄酮类化合物在内的植物化学物质类别进行了更完整的描述。

 

Maximum studies have used black raspberries, though, other berry types such as strawberries, blackberries, blueberries, red raspberries, acai and others are also accomplished of preventing cancer. Initially, a series of berry extracts were shown to decrease the production rate of cancer cells in vitro and/or to stimulate apoptosis. The inhibitory potential of these extracts was frequently attributed to their content of ellagitannins or anthocyanins. Preclinical studies confirmed that freezedried berry powders were effective in avoiding chemical carcinogen-induced cancer in the rodent oral cavity, esophagus, and colon, and an anthocyanin-rich extract inhibited UV-induced skin cancer in mice. Mechanistic studies showed that the berries prevented the conversion of premalignant lesions in rodent tissues to malignancy by reducing cell proliferation, inflammation, and angiogenesis and by stimulating apoptosis and cell differentiation. Multiple genes associated with all of these cellular functions are protectively modulated by berries. For example, berries down-regulate the expression levels of genes in the P13K/Akt, MAPK, ERK ½, AP-1 and mTOR signaling pathways (proliferation), COX-2, iNOS, NF-κB, IL-1β and IL-12 (inflammation), VEGF and HIF-1α (angiogenesis), and up regulate caspase 3/7 and Bax (apoptosis), and both keratin and mucus-associated genes for squamous and glandular differentiation, respectively. Bio-fractionation studies indicate that the most active inhibitory compounds in berries are the anthocyanins and ellagitannins. The fiber fraction of berries is also active in preventing cancer in rodents and study is needed to recognise the active polysaccharides in this fraction. Human clinical trials indicate that freeze-dried berry formulations elicit little or no toxicity in humans when administered in the diet at concentrations as high as 60g/day for as long as nine months. The endorsement of berry anthocyanins and ellagic acid into blood is rapid but minimal; i.e., less than 1% of the controlled dosage. Almost 70% of the ordered anthocyanins are metabolized by the enteric bacteria into protocatechuic acid (PCA) that has substantial cancer preventative activity. Black raspberry formulations have exposed to cause histologic regression of oral leukoplakic lesions in the oral cavity, dysplastic lesions in the esophagus, and polyps in the rectum of patients with familial adenomatous polyposis. These results are very promising and the mechanisms for these effects will be discussed.

 

Strawberry, blackberry, and blueberry powders are also tested for their capability to inhibit NMBA tumorigenesis in the rat esophagus when added at 5 and 10% of the diet. Strawberries and blackberries were approximately as active in preventing tumors as BRB. However, blueberries were inactive. Both straw-berries and blackberries reduced the formation of NMBA induced O -MeGua adducts in esophageal DNA; whereas blueberries had no effect on adduct formation. The reason(s) for the inactivity of blueberries is unknown. Apart from the other three berry types, there are too low levels of ellagitannins in blueberries. In addition, blueberry anthocyanins have a delphinid in skeleton whereas the anthocyanins in BRB and blackberries have a cyanidin skeleton and those in strawberries have both pelaro-gonidin and cyanidin skeletons. These alterations in chemical arrangement may be responsible for the different biological activities of the berry types. A second bioassay using blueberries is now being utilized to confirm the previous results and further determines the basis for the inactivity of blueberries.

 

Effects of Freeze-Dried Strawberries, Blackberries, and Blueberries on NMBA-Induced Rat Esophageal Tumorigenesis when Administered in the Diet Before, During, and 712 Part IV / Other Bioactive Food Components in Cancer Prevention and/or Treatmentusing blueberries is currently being utilized to confirm the previous results and furtherdetermine the basis for the inactivity of blueberries.

 

事实证明，无论是啮齿类动物还是人类，肺癌的化学预防都很困难。因此，含有 10% 冻干草莓的饮食无法减少由 4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁酮 (NNK) 或苯并 (a) 芘 (B(a)P) 诱发的小鼠的肺癌，这也许并不奇怪。在这项研究中，从初始致癌物治疗前一周开始，并在整个研究过程中，A/J 品系小鼠开始食用草莓饮食。从生物测定的第 2 周开始，在 2 周内腹腔内施用 NNK 和 B(a)P。在 24 周时，任何组的肺癌发病率或多发性均无差异。浆果成分直接与组织接触，成功减少了口腔、食道和结肠中致癌物诱发的癌症，但未能抑制小鼠的肺癌，这表明浆果中的活性成分未能以足够的量到达肺部以引起保护。研究支持了这一推论，研究表明，浆果汁中的花青素和鞣花单宁在啮齿动物中吸收不良，其血浆水平迅速下降。然而，膳食 BRB 粉对大鼠雌激素介导的乳腺癌的屏蔽作用表明，通过全身输送，足够量的保护性化合物到达乳腺。因此，膳食浆果粉的保护作用似乎取决于器官和部位。此外，还将讨论利用浆果预防癌症的临床应用的收益和遭遇，并为未来的试验提出建议。

 

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斯托纳是威斯康星医学院 (MCW) 血液学和肿瘤学系的医学教授，专攻化学致癌作用和癌症化学预防领域。他担任新成立的癌症中心分子致癌作用和化学预防项目主任。斯托纳在加入 MCW 之前，曾在俄亥俄州立大学医学院工作近 20 年，担任癌症研究和治疗 Lucius Wing 特聘教授、癌症中心基础研究副主任和化学预防项目主任，以及环境健康科学系主任和公共卫生学院研究副院长。

注：该研究部分在 2015 年 10 月 26 日至 28 日在美国伊利诺伊州芝加哥举行的第四届国际营养会议和展览会上展示。