植物化学物与健康

1、植物化学物与健康,朱俊东 教授 第三军医大学营养与食品安全研究中心,2020/7/9,五颜六色的果蔬,2020/7/9,神奇的植物色素,叶绿素类：主要有叶绿素a、叶绿素b 类胡萝卜素类：主要有类胡萝卜素和叶黄素 类黄酮类色素：主要有花青素类色素和花黄素类色素,2020/7/9,法国悖论（French paradox）,上世纪80年代科学家们发现尽管法国人同其他发达国家的居民一样，通过食物摄取了大量的高脂肪、高蛋白、高能量的食物，但他们的心血管病发病率却比美国、英国等其他发达国家低得多。,Renaud S, de Lorgeril M. Wine, alcohol, platelets, and

2、 the French paradox for coronary heart disease. Lancet，1992；339(8808):1523-1526.,2020/7/9,Oyebode O, Gordon-Dseagu V, Walker A, Mindell JS. Fruit and vegetable consumption and all-cause, cancer and CVD mortality: analysis of Health Survey for England data. J Epidemiol Community Health. 2014;68(9):85

3、6-862. Bellavia A, Larsson SC, Bottai M, Wolk A, Orsini N. Fruit and vegetable consumption and all-cause mortality: a dose-response analysis. Am J Clin Nutr. 2013;98(2):454-459,蔬菜水果降低慢性病风险的作用成分有哪些？,维生素 矿物质 膳食纤维 ？,What food is required for me? Nutritional deficiency: Iron - Anemia Iodine Thyroid goit

4、er Vitamin D - Rickets Identifying essential nutrients required for promoting growth and sustaining life. Vitamins Essential minerals Calcium Essential amino acids,1920s-1980s,What does food do to me? Nutritional excess and imbalances Calories - obesity Fiber Colon cancer Identifying nutrients and c

5、omponents that contribute to premature death Saturated fat Cholesterol Sodium,1950s-1990s,What does food do for me? Nutritional optimization of quality of life Identification of physiological active components to prevent or delay premature onset of chronic disease Phytochemicals Prebiotics Fiber,199

6、0s-Today!,植物化学物（phytochemicals） -第八类营养素？,对植物化学物的研究是全球范围内发展最快速的一个领域，同样，植物化学物质在营养学界也是非常令人兴奋的一个新兴领域。 -美国营养学家David Richardson博士,内容提要 1. 植物化学物概述 2. 植物化学物的健康效应 3. 膳食建议,一、植物化学物概述 植物化学物的概念和分类,2020/7/9,初级代谢 (primary metabolism ) 是一类发生在生长繁殖期的普遍存在于一切生物中的代谢类型。 初级代谢产物 (Primary metabolites) 主要是碳水化合物、蛋白质和脂肪。它们是机体生

7、存必不可少的营养物质。,次级代谢 (secondary metabolism) 生物为避免在初级代谢过程中某些中间积累所造成不利作用或外环境因素胁迫而产生的一类有利于生存的代谢类型。 次级代谢产物 (Secondary metabolites) 是生物进化过程中植物维持其与周围环境（包括紫外线)相互作用的生物活性分子。,2020/7/9,植物化学物的作用： 保护其不受杂草、昆虫、及微生物侵害 作为植物生长调节剂 形成植物色素 维系植物与其生长环境之间的相互作用 植物化学物的特点： 种类多，数量少（6-10万种，摄入量1.5g/d） 对人体健康具有双重作用,2020/7/9,植物化学物分类,二、

8、植物化学物的健康保护效应,1.天然抗氧化剂,自由基的产生,2020/7/9,机体抗氧化系统,2020/7/9,2020/7/9,癌症 心血管疾病 糖尿病 衰老 高血压 老年性痴呆 白内障 类风湿性关节炎,植物化学物是机体抗氧化的强力外援,人体每天摄入的传统抗氧化营养素大约为100mg 人体每天摄入的抗氧化植物化学物超过1g 外源抗氧化摄入水平：植物化学物是营养素的10倍,原花青素（OPC） 抗氧化能力约是VE的50倍、VC的20倍 蕃茄红素 抗氧化能力是VE的100倍，-胡萝卜素的3.2倍,吃葡萄不吐葡萄皮,一些水果的抗氧化力比较,FRAP(Ferric reducing antioxidan

9、t potential Assay),一些蔬菜的抗氧化作用比较,ORAC（Oxgen Radical Absorbance Capacity）,2020/7/9,每天吃8份果蔬（约700克）可以使心脏病死亡率降低22%； 每天吃3个苹果可以使心脏病发病率降低14，冠心病的死亡率降低27。,2.保护心脑血管健康,2020/7/9,Zhou X, Chen M, Zeng X, et al. Resveratrol regulates mitochondrial reactive oxygen species homeostasis through Sirt3 signaling pathway

10、in human vascular endothelial cells. Cell Death Dis. 2014;5:e1576.,2020/7/9,Jin X, Yi L, Chen ML, et al. Delphinidin-3-glucoside protects against oxidized low-density lipoprotein-induced mitochondrial dysfunction in vascular endothelial cells via the sodium-dependent glucose transporter SGLT1. PLoS

11、One. 2013;8(7):e68617.,3.抗肿瘤作用 每天吃5份不同的果蔬可以使肺癌的发病率降低23%！ 一天吃一个番茄可以使前列腺癌发生率降低26%！ 每天吃2份水果和5份蔬菜，可大大降低患肠癌的几率。,进食水果与肺癌死亡的危险度,*美国癌症协会100万人前瞻观察十年研究结果,2020/7/9,藤茶，葡萄科葡萄属显齿蛇葡萄科的嫩茎叶。主要生长在中国江南山区各地。其味甘甜性凉，具有清热解毒、抗菌消炎、降血糖、降血脂、保肝护肝等功效。,2020/7/9,2020/7/9,2020/7/9,2020/7/9,4.抗辐射作用 1945年8月，一颗原子弹使广岛10万多人丧生，若干年后大多数人患

12、上白血病或其他癌症，先后死亡。但研究却发现茶农、茶商、茶癖者侥幸无恙。这种特殊的关联性被称为“广岛现象”。,5.雌激素样作用 美国女性的乳腺肿瘤发生率历来是中国和日本妇女的4-7倍，大豆饮食在其中发挥了不可低估的作用。,雌激素女性的保护伞,化学结构：属于黄酮类化合物 食物来源：大豆及豆制品 生物学性质：属于植物雌激素 种类：染料木黄酮、大豆苷元、黄豆黄素,（一）改善更年期综合症,明显改善潮热等症状（19项 RCT-Meta分析）,（二）改善骨质疏松,补充富含大豆异黄酮的食物或提取物（苷元80mg/d）1年以上，腰椎骨密度有明显改善；更年期和绝经后女性补充大豆异黄酮后可以抑制骨吸收和促进骨形成（

13、 10项 RCT-Meta分析）。,（三）降低乳腺癌和前列腺癌的发病风险,与亚洲女性乳腺癌的发病率存在负相关，而在西方女性不存在相关性；与绝经后女性乳腺癌的发病率和复发率较低有关，而在绝经前女性不存在相关性（前瞻性流行病学研究Meta分析）。,2020/7/9,6、抑制微生物作用,大蒜素杀菌能力是青霉素的1/10，对多种致病菌如葡萄球菌、脑膜炎、肺炎、链球菌及白喉、痢疾杆菌等都有明显的抑制和杀灭作用。,2020/7/9,姜黄（姜黄素，curcumin）,生姜,姜黄素对葡萄球菌有较好的抑制和杀灭作用,2020/7/9,植物化学物主要作用,植物化学物运动模拟剂？,营养促进肌纤维类型转换？,线粒体动

14、力加工厂,Lin et al. (2002,Nature) generated transgenic mice that overexpressed PGC-1 in their muscles. In the figures, WT refers to the wildtype and TG to the transgenic mice. The transgenic muscles have more cytochrome c, an enzyme found in mitochondria. These data show that PGC-1 can induce mitochondr

15、ial biogenesis in vivo.,WT TG,PGC-1与线粒体生物合成,Overexpression of PGC-1 did not only affect mitochondrial biogenesis.The transgenic muscles appear red due to the high myoglobin content. The mitochondrial content is increased as expected and surprisingly also motor proteins such as slow troponin (TnI) an

16、d slow myosin are upregulated (Lin et al. 2002).,Fig1.Peroxisome proliferator-activated receptor (PPAR)- coactivator-1 (PGC-1) transgenic mice exhibit greater exercise capacity during multiple exercise paradigms.,Calvo JA,et al.Muscle-specific expression of PPARgamma coactivator-1alpha improves exer

17、cise performance and increases peak oxygen uptake. J Appl Physiol.2008,104(5):1304-12.,Fig2. PGC-1 transgenic mice exhibit greater peak Vo2 and decreased respiratory exchange ratio (RER) values during exercise.,Calvo JA,et al.Muscle-specific expression of PPARgamma coactivator-1alpha improves exerci

18、se performance and increases peak oxygen uptake. J Appl Physiol.2008,104(5):1304-12.,Wang YX,et al. Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol.2004,2(10):e294.,Fig1. Increased Oxidative Type I Fibers in the Transgenic Mice (A and B) Muscles in transgenic mice (TG)

19、are redder than those in wild-type mice (WT). (C) Metachromatic staining of the type II plantaris muscle. Type I fibers are stained dark blue.,Fig2. PPAR Regulates Exercise Endurance (A) Enhanced exercise performance in the transgenic mice. Fourteen-week-old male transgenic and wild-type littermates

20、 with similar body weights (n= 4 for each group) were subjected to a forced treadmill exercise test. (B) Compromised exercise performance in PPAR-null mice. Two-month-old male PPAR-null mice and wild-type controls with similar body weights (n= 6 for each group) were subjected to a forced treadmill e

21、xercise test. (C) Functions of PPAR in skeletal muscle.,耐力训练与PGC-1,PGC-1,AMPK,CamK,p38,Endurance exercise,AMP-activated protein kinase (AMPK; Terada et al. 2003) and Calcium/calmodulin-activated kinase (CamK IV; Wu et al. 2003) have been shown to stimulate PGC-1 expression. The action of p38 MAPK le

22、ads to an increased phosphorylation of PGC-1 (Puigserver et al. 2003).,The following figure shows that swimming and AICAR, an AMPK activator, increase PGC-1 (Terada et al. 2002).,Fig1.AICAR increases running endurance C57Bl/6J mice were treated with vehicle (open bars/thin lines) or AICAR (500mg/kg/

23、day, 4 weeks) (closed bar/thick lines).(D)Oxygen consumption rates (mg/kg/hr) measured over 12 hr period.(E)Data in(D)is represented as AUC.(F)Running endurance measured as a function of time (upper panel) and distance (lower panel).(G)Representative oxidative genes induced by AICAR treatment (250 m

24、g/kg/day, 6 days).,Narkar VA,et al.AMPK and PPARdelta agonists are exercise mimetics. Cell.2008,134(3):405-15.,Fig2 . PPAR activation in mice (C)Representative meta-chromatically stained frozen gastrocnemius cross-sections from vehicle-treated sedentary(V), GW1516-treated sedentary(GW), vehicle-trea

25、ted exercised(Tr)and GW-treated exercised(Tr+GW)mice. Type I fibers are stained dark blue.(D)Type I fiber quantification (N=3).(E)Fold change in mitochondrial DNA to nuclear DNA ratio (N=9).,Wu et al. (2002) generated transgenic mice that overexpressed calmodulin-dependent kinase IV (CaMk IV) in the

26、ir muscles. In the figures, WT refers to the wildtype, the normal mouse and TG to the transgenic mouse. The transgenic mice had more mitochondria in their muscles. In addition they measure the cytochrome B gene DNA which is a marker for the mitochondrial DNA content.,?,PGC-1,NRF,mtTFA,AMPK,CamK,p38,Mitochondrial biogenesis,Endurance exercise,PGC-1,An increased PGC-1 concentration then expression of NRF-1, NRF-2 and mtTFA, i.e. transcription factors that regulat