MORINGA LEAF OR SEED EXTRACT

辣木叶或种子提取物

• 批准号: 7604638
• 负责人: PAUL TALALAY
• 金额: $ 0.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604638
• 关键词: Advocate; Afghanistan; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibiosis; Antibiotics; Antihypertensive Agents; Area; Ascorbic Acid; Asia; Bangladesh; Benzyl Compounds; Biopsy; Botanicals; Broccoli - dietary; Burkitt Lymphoma; Cabbage - dietary; Carcinogens; Caribbean natives; Caribbean region; Caring; Carotenoids; Cell Line; Cells; Chemical Agents; Chemoprotection; Chemoprotective Agent; Church; Comet Assay; Computer Retrieval of Information on Scientific Projects Database; Consumption; Cultured Cells; Cytochrome P450; DNA; Data; Development; Dietary Isothiocyanate; Dietary Phytochemical; Dose; Drug Kinetics; Eating; Edible Plants; Effectiveness; Enzymes; Epstein-Barr virus early antigen; Ethiopia; Ethnobotany; European; Exudate; Familiarity; Family; Fever; Flocculation; Florida; Folk Medicine; Food; Funding; Glucosinolates; Glucuronosyltransferase; Glutathione; Glutathione Metabolism Pathway; Glutathione Reductase; Glutathione S-Transferase; Goals; Grant; Greek; Hair; Horseradish; Human; Human Volunteers; Hunger; Hypoglycemia; Hypoglycemic Agents; India; Indigenous; Infant; Institution; Isothiocyanates; Kale - dietary; Kinetics; Knowledge; Laboratories; Latin America; Left; Literature; Liver; Location; Lubrication; Lymphocyte; Malignant Neoplasms; Malnutrition; Measurable; Measures; Methods; Modeling; Moringa; Moringa oleifera; Mothers; Mus; NAD(P)H Dehydrogenase (Quinone); Numbers; Nurses; Nutritional; Oils; Organ; Pacific Islands; Pakistan; Perfume; Peripheral; Pharmacology; Phase; Philippines; Phorbol Esters; Phytochemical; Plant Leaves; Plant Preparations; Plant Roots; Plasma; Powder dose form; Predisposition; Preparation; Preventive; Proteins; Purpose; Quinone Reductases; Recording of previous events; Refrigeration; Relative (related person); Research; Research Personnel; Resources; Risk; Rodent; Sampling; Schistosoma; Scientist; Seasons; Sedimentation process; Seeds; Services; Site; Skin; Source; South Africa; Spasmolytics; Staging; Sudan; Sulforaphane; Tea; Testing; Therapeutic; Tissues; Topical application; Traditional Medicine; Trees; Tumor Promotion; United States National Institutes of Health; Urine; Validation; Vegetables; Water Purification; Weight; base; benzyl isothiocyanate; cancer risk; cooking; cruciferous vegetable; desire; detoxication; drinking water; healthy volunteer; indexing; inhibitor/antagonist; keratinocyte; member; milligram; neoplastic; nutrition; oral tolerance; reactive oxygen intermediate; response; tumor; uptake; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The development of strategies to reduce the risk of cancer by administration of dietary phytochemicals that elevate the activities of Phase 2 detoxication enzymes and the tissue levels of glutathione has been a long-standing goal of this laboratory (1). We have designated this strategy as "chemoprotection." A large body of evidence demonstrates that the susceptibility of animals and their cells to the toxic and neoplastic effects of electrophilic carcinogens and reactive oxygen intermediates can be substantially reduced by raising cellular glutathione (GSH) levels and the activities of Phase 2 enzymes (e.g., glutathione transferases, glucuronosyltransferases, and quinone reductase) (2). Our laboratory has shown that a variety of chemical agents induce Phase 2 enzymes and raise GSH levels without significantly influencing the activities of Phase 1 cytochromes P450 (3). A substantial number of these inducers are present in edible plants, especially in cruciferous vegetables (e.g., broccoli, cabbage, Brussels sprouts, kale) and their widely distributed, close botanical relatives (e.g. Moringa sp.) (4-6). There is mounting evidence that the capacity of these phytochemicals to raise Phase 2 enzymes may be in part responsible for the well-recognized protection against cancer afforded by consumption of large quantities of vegetables (7). As described in RPN # 03-05-28-03, broccoli contains an isothiocyanate, known as sulforaphane, which is one of the most potent naturally occurring Phase 2 inducers (8) and it inhibits chemically induced tumor formation in response to several carcinogens (9-12). More recently, we discovered that Moringa sp. contain an isothiocyanate, 4-(rhamnopyranosyloxybenzyl) isothiocyanate [4RBITC], which is at least as potent an inducer of Phase 2 enzymes as sulforaphane in multiple animal cell lines (13). We have developed analytical and preparative methods for producing this isothiocyanate and its cognate glucosinolate (14) and we have shown that it is taken up by cultured animal cells with similar uptake kinetics to those of sulforaphane (J.W. Fahey, unpublished observation). Moreover, and in contrast to broccoli, topical application of Moringa sp. preparations (e.g. root exudates, seed oil, bark, and leaf homogenates and extracts) have been utilized for medicinal purposes for centuries (15-19). We now wish to apply extracts of leaves of the Moringa tree to the skin of normal volunteers to establish whether Phase 2 enzymes are induced and glutathione levels are elevated in biopsies of the skin. Ethnobotany, Pharmacology, and Nutritional Value. The most common species is Moringa oleifera. All parts of the Moringa tree are edible and have long been consumed by humans, this tree has recently been advocated as an outstanding indigenous source of highly digestible protein, Ca, Fe, Vitamin C, and carotenoids in many undernourished "developing" regions of the world (17). Moringa trees also have a long history of traditional medicinal use in these areas of the tropics (17,18). We propose to develop the chemoprotective potential of [1] and closely related glucosinolates from Moringa species. Since familiarity with Moringa is quite limited among scientists, we summarize the present state of knowledge below. Moringa oleifera, the most widely cultivated species, is a member of a monogeneric family, the Moringaceae, that is native to the sub-Himalayan tracts of India, Pakistan, Bangladesh and Afghanistan. This rapidly-growing tree (also known as the horseradish, drumstick, or Ben oil tree), was cultivated and utilized by the ancient Romans, Greeks and Egyptians; it is now widely cultivated and has become naturalized in many locations in the tropics. It is a perennial softwood tree with timber of low quality, but which for centuries has been advocated for traditional medicinal and industrial uses. It is already an important crop in India, Ethiopia, the Philippines and the Sudan, and is being grown in West, East and South Africa, tropical Asia, Latin America, the Caribbean, Florida and the Pacific islands. Moringa trees have been used to combat malnutrition, especially among infants and nursing mothers. Non-governmental organizations such as Church World Service (CWS) and Educational Concerns for Hunger Organization (ECHO) have advocated Moringa as "natural nutrition for the tropics." Leaves can be eaten fresh, cooked, or stored as dried powder for many months without refrigeration, and apparently without loss in nutritional value. Moringa is especially promising as a food source in the tropics because the tree is in full leaf at the end of the dry season when other foods are typically scarce. Moringa seed oil (yield 30-40%, by weight), also known as Ben oil, is a sweet non-sticking, non-drying oil, that resists rancidity, and has been used in salads, for fine machine lubrication, and in the manufacture of perfume and hair care products (20). Powdered seeds are used to flocculate contaminants and purify drinking water (21-23). Seeds are also eaten green, roasted, powdered and steeped for tea or used in curries, and used by Europeans to treat fever (21). Widespread claims for the medicinal effectiveness of various Moringa tree preparations support our desire to concentrate on the potential cancer preventive activity of this family and its glucosinolates. A plethora of traditional medicine references attest to its curative power, and scientific validation of these popular uses is developing to support at least some of the claims. Moringa preparations have been cited in the scientific literature as having antibiotic (24-28), antitrypanosomal (29), hypotensive (30-32), antispasmodic (33), antiulcer (34), anti-inflammatory (33,35), hypocholesterolemic (36), and hypoglycemic (37) activities as well as having considerable efficacy in water purification by flocculation, sedimentation, antibiosis and even reduction of schistosome cercariae titer (21,23,26). Specific components of these Moringa preparations that were active as hypotensives include 4-[(4'-O-acetyl-?-L-rhamnopyranosyloxy)benzyl] isothiocyanate [2] (30). Moringa species have long been recognized by folk medicine practitioners as a tumor therapeutic (26,35). Recently, 4-(?-L-rhamnopyranosyloxy)-benzyl isothiocyanate, [3] 4-[(4'-O-acetyl-?-L-rhamnopyranosyloxy)benzyl] isothiocyanate and the related 4-(?-L-rhamnopyranosyloxy)benzyl compound, niazimicin, were shown to be potent inhibitors of phorbol ester (TPA)-induced Epstein-Barr virus-early antigen activation in lymphoblastoid (Burkitt's lymphoma) cells (38,39). In one of these studies, niazimicin also inhibited tumor promotion in the mouse two-stage DMBA-TPA model but the cognate isothiocyanate was not tested (38). We have previously conducted a pharmacokinetic study at Johns Hopkins on healthy volunteers to obtain pilot data on the effects of dietary isothiocyanates on Phase 2 enzymes and on indicators of oxidative damage (oxidized DNA bases and Comet assays of DNA) in lymphocytes (RPN 98-12-03-01). We have also obtained data on oral tolerance of repetitive doses of isothiocyanates on healthy human volunteers (40,41). The findings are summarized under "Risks" and give no cause for concern about tolerance. We have however been concerned that isothiocyanates may not reach the target tissues. These compounds may be metabolized by the gut and liver before they reach the compartments we are sampling (plasma, lymphocytes, urine) (42,43). Thus, plant preparations rich in isothiocyanates (e.g. Moringa leaf or seed extracts) may enhance detoxication capacity in organs of first defense (gut, liver), but their effects may not be apparent in peripheral sites. We have therefore searched for more direct methods for assessing effects on Phase 2 activities. We have shown that primary human skin culture cells (obtained commercially) as well as cultured rodent and human keratinocytes are induced by low levels of an isothiocyanate with respect to quinone reductase activity and glutathione levels (unpublished observations). These are parameters that are easily measurable on a few milligrams of tissue. These findings encourage us to examine the feasibility of measuring these indices of Phase 2 activity as well as enzymes concerned with glutathione metabolism (glutathione reductase and glutathione transferases) in human skin biopsies, following topical application of Moringa leaf or seed extracts containing 4RBITC.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 通过饮食中植物化学物质的给药来降低癌症风险的策略，从而提高了2阶段解毒酶的活性和谷胱甘肽的组织水平一直是该实验室的长期目标（1）。我们将此策略指定为“化学保护”。大量证据表明，通过提高细胞谷胱甘肽（GSH）水平以及2阶段2酶的活性，可以大大降低动物及其细胞对亲电癌和活性氧中间体的毒性和肿瘤作用的敏感性（例如，谷胱甘肽，谷胱甘肽转移酶，Glucuronysylsyltrases，quinaneseanseffersefferase，quinaneseanseants＆quinorese asseferase），可以大大降低。我们的实验室表明，多种化学剂会诱导2期酶并提高GSH水平，而不会显着影响1期细胞色素P450的活性（3）。这些诱导剂中有大量的可食用植物存在，尤其是十字花科蔬菜（例如西兰花，白菜，布鲁塞尔芽菜，羽衣甘蓝）及其广泛分布的，近亲的亲戚（例如，莫林加sp。）（4-6）（4-6）。有越来越多的证据表明，这些植物化学物质升高2期酶的能力可能部分是由于消费大量蔬菜所提供的公认的保护良好的保护（7）。如RPN＃03-05-28-03中所述，西兰花含有异硫氰酸酯，称为硫烷，它是最有效的自然发生的2期2诱导剂（8），它抑制了对几种致癌物（9-12）响应的化学诱导肿瘤形成。 最近，我们发现了Moringa sp。含有异硫氰酸盐，4-（hamnopyranosyloxybenzyl）异硫氰酸酯[4RBITC]，至少在多个动物细胞系中，至少是2期酶的诱导剂（13）。 我们已经开发了产生这种异硫氰酸酯及其同源葡萄糖苷的分析和制备方法（14），并且我们表明，它是由具有与硫磷酸盐相似摄取动力学的培养的动物细胞所采用的（J.W. Fahey，未发表的观察结果）。 此外，与西兰花相比，辣木sp的局部应用。几个世纪以来，已经将制剂（例如根渗出液，种子油，树皮和叶子匀浆和提取物）用于药用目的（15-19）。 现在，我们希望将辣木树叶子的叶子提取到正常志愿者的皮肤上，以确定是否诱导了2期酶，并且在皮肤活检中，谷胱甘肽水平升高。 民族植物学，药理学和营养价值。最常见的物种是Moringa oleifera。 辣木树的所有部分都是可食用的，长期以来一直被人类食用，最近被提倡是许多不足的世界“发展中”地区的高度消化蛋白，CA，FE，VETAMIN C和类胡萝卜素的杰出土著来源（17）。辣木树在热带地区的这些领域也有悠久的传统药用历史（17,18）。我们建议从辣木物种发展[1]和密切相关的葡萄糖醇的化学保护潜力。由于科学家中对辣木的熟悉程度非常有限，因此我们总结了 以下知识状态。 莫林加·奥利法拉（Moringa oleifera）是一种最广泛的种植物种，是一个单基因家族的成员，是辣木科，它原产于印度，巴基斯坦，孟加拉国和阿富汗的亚马里亚山脉。这棵快速生长的树（也称为辣根，鼓槌或本油树）被古罗马人，希腊人和埃及人种植和利用。现在，它已被广泛培养，并且已经在热带地区的许多地方归化。这是一棵多年生的软木树，具有低品质的木材，但几个世纪以来一直倡导传统的药用和工业用途。它已经是印度，埃塞俄比亚，菲律宾和苏丹的重要作物，并且正在西，东非和南非，热带亚洲，拉丁美洲，加勒比海，佛罗里达州和太平洋群岛种植。 辣木已被用来打击营养不良，尤其是在婴儿和护理母亲中。非政府组织，例如教会世界服务（CWS）和饥饿组织（ECHO）的教育问题，已主张莫林加作为“热带地区的自然营养”。 叶子可以新鲜，煮熟或作为干粉储存多个月而无需制冷，显然没有营养价值损失。在热带地区，辣木作为食物来源尤其有希望，因为在干旱季节结束时，当其他食物通常稀少时，树在全叶中。 辣木种子油（重量为30-40％），也称为Ben Oil，是一种甜美的非粘液，非干燥油，可抵抗腐烂的味道，并已用于沙拉中，用于精细的机器润滑，并用于制造香水和护发产品（20）。粉状种子用于絮凝污染物并净化饮用水（21-23）。 种子也被食用绿色，烤，粉末，浸泡在茶或咖喱中，并由欧洲人用来治疗发烧（21）。 关于各种辣木制剂的药物有效性的广泛主张，支持我们专注于该家族及其葡萄糖醇的潜在癌症预防活性的愿望。大量传统医学参考证明了其治愈能力，对这些流行用途的科学验证正在发展，以支持至少某些主张。在科学文献中引用了辛加的制剂为具有抗生素（24-28），抗丙糖体（29），降压（30-32），抗痉挛性（33），抗溶剂（34），抗炎（34），抗炎症（33,35），抗炎（33,35），次降低（36）和次型（36），并具有较高的（37），并有效地促进了效果（37）。通过絮凝，沉积，抗抗病，甚至还原黑素尾cercariae滴度（21,23,26）。 这些作为低敏性活性的这些辣木制剂的特定组成部分包括4 - [（4'-o-o-acetyl - ？ - l-rhamnopyranosyoxy）苄基]异硫氰酸酯[2]（30）。 辣木物种长期以来被民间医学认可 从业者作为肿瘤治疗（26,35）。 最近，4-（？ - l-rhamnopyranosyoxy） - 异硫氰酸酯，[3] 4-- [（（4'-o-乙酰基 - ？ - l-rhamnopyranosyolxy）苯甲酰氧基]苄烯酸）]异硫氰酸盐和相关的4-（ - ？佛波尔酯（TPA）诱导的爱泼斯坦 - 巴尔病毒 - 早期抗原活化的抑制剂在淋巴母细胞（伯基特的淋巴瘤）细胞中（38,39）。 在其中一项研究中，niazimicin还抑制了小鼠两阶段DMBA-TPA模型中的肿瘤促进，但未测试异硫氰酸酯（38）。 我们以前曾在约翰·霍普金斯（Johns Hopkins）对健康志愿者进行一项药代动力学研究，以获取有关饮食异硫氰酸酯对2阶段酶的影响以及氧化损伤指标（氧化DNA碱基和DNA的彗星分析）在淋巴细胞中（RPN 98-12-03-03-03-01）的影响。我们还获得了关于健康人类志愿者的重复剂量异硫氰酸盐的口服耐受性的数据（40,41）。这些发现是在“风险”下总结的，没有引起人们对容忍度的关注。 但是，我们一直担心异硫氰酸盐可能无法到达目标组织。 这些化合物可以通过肠道和肝脏代谢，然后它们到达我们要采样的室（血浆，淋巴细胞，尿液）（42,43）。因此，富含异硫氰酸酯（例如辣木或种子提取物）的植物制剂可能会增强第一防御器官（肠道，肝脏）的解毒能力，但它们的作用在外周部位可能并不明显。因此，我们已经搜索了更直接的方法来评估对2阶段活动的影响。我们已经表明，原发性人类皮肤培养细胞（商业上获得）以及培养的啮齿动物和人角质形成细胞是由低水平的异硫氰酸盐诱导的，相对于奎诺酮还原酶活性和谷胱甘肽水平（未发表的观察结果）。这些是在几毫克组织上易于测量的参数。这些发现鼓励我们检查与谷胱甘肽代谢（谷胱甘肽还原酶和谷胱甘肽转移酶）在人类皮肤活检中相关的酶的可行性以及与谷胱甘肽代谢（谷胱甘肽还原酶和谷胱甘肽转移酶）有关的酶，此外是借助莫林加叶或含有4rbitc的种子提取物的局部应用。