Tea catechin auto-oxidation dimers are accumulated and retained by Caco-2 human intestinal cells

Despite the presence of bioactive catechin B-ring auto-oxidation dimers in tea, little is known regarding their absorption in humans. Our hypothesis for this research is that catechin auto-oxidation dimers are present in teas and are absorbable by human intestinal epithelial cells. Dimers (theasinensins [THSNs] and P-2 analogs) were quantified in commercial teas by high-performance liquid chromatography-mass spectrometry. (−)-Epigallocatechin (EGC) and (−)-epigallocatechin gallate (EGCG) homodimers were present at 10 to 43 and 0 to 62 μmol/g leaf, respectively. The EGC-EGCG heterodimers were present at 0 to 79 μmol/g. The potential intestinal absorption of these dimers was assessed using Caco-2 intestinal cells. Catechin monomers and dimers were detected in cells exposed to media containing monomers and preformed dimers. Accumulation of dimers was significantly greater than monomers from test media. Three-hour accumulation of EGC and EGCG was 0.19% to 0.55% and 1.24% to 1.35%, respectively. Comparatively, 3-hour accumulation of the EGC P-2 analog and THSNs C/E was 0.89% ± 0.28% and 1.53% ± 0.36%, respectively. Accumulation of P-2 and THSNs A/D was 6.93% ± 2.1% and 10.1% ± 3.6%, respectively. The EGCG-EGC heterodimer P-2 analog and THSN B 3-hour accumulation was 4.87% ± 2.2% and 4.65% ± 2.8%, respectively. One-hour retention of P-2 and THSNs A/D was 171% ± 22% and 29.6% ± 9.3% of accumulated amount, respectively, suggesting intracellular oxidative conversion of THSNs to P-2. These data suggest that catechin dimers present in the gut lumen may be readily absorbed by intestinal epithelium.     

Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent Metabolic Syndrome

Obesity and being overweight are linked with a cluster of metabolic and vascular disorders that have been termed the metabolic syndrome. This syndrome promotes the incidence of cardiovascular diseases that are an important public health problem because they represent a major cause of death worldwide. Whereas there is not a universally-accepted set of diagnostic criteria, most expert groups agree that this syndrome is defined by an endothelial dysfunction, an impaired insulin sensitivity and hyperglycemia, dyslipidemia, abdominal obesity and hypertension. Epidemiological studies suggest that the beneficial cardiovascular health effects of diets rich in green tea are, in part, mediated by their flavonoid content, with particular benefits provided by members of this family such as epigallocatechin gallate (EGCG). Although their bioavailability is discussed, various studies suggest that EGCG modulates cellular and molecular mechanisms of various symptoms leading to metabolic syndrome. Therefore, according to in vitro and in vivo model data, this review attempts to increase our understanding about the beneficial properties of EGCG to prevent metabolic syndrome.     

Structure-activity relationships for inhibition of human 5alpha-reductases by polyphenols

The enzyme steroid 5 alpha-reductase (EC 1.3.99.5) catalyzes the NADPH-dependent reduction of the double bond of a variety of 3-oxo-Delta(4) steroids including the conversion of testosterone to 5 alpha-dihydrotestosterone. In humans, 5 alpha-reductase activity is critical for certain aspects of male sexual differentiation, and may be involved in the development of benign prostatic hyperplasia, alopecia, hirsutism, and prostate cancer. Certain natural products contain components that are inhibitors of 5 alpha-reductase, such as the green tea catechin (-)-epigallocatechin gallate (EGCG). EGCG shows potent inhibition in cell-free but not in whole-cell assays of 5 alpha-reductase. Replacement of the gallate ester in EGCG with long-chain fatty acids produced potent 5 alpha-reductase inhibitors that were active in both cell-free and whole-cell assay systems. Other flavonoids that were potent inhibitors of the type 1 5alpha-reductase include myricetin, quercitin, baicalein, and fisetin. Biochanin A, daidzein, genistein, and kaempferol were much better inhibitors of the type 2 than the type 1 isozyme. Several other natural and synthetic polyphenolic compounds were more effective inhibitors of the type 1 than the type 2 isozyme, including alizarin, anthrarobin, gossypol, nordihydroguaiaretic acid, caffeic acid phenethyl ester, and octyl and dodecyl gallates. The presence of a catechol group was characteristic of almost all inhibitors that showed selectivity for the type 1 isozyme of 5 alpha-reductase. Since some of these compounds are consumed as part of the normal diet or in supplements, they have the potential to inhibit 5 alpha-reductase activity, which may be useful for the prevention or treatment of androgen-dependent disorders. However, these compounds also may adversely affect male sexual differentiation.     

EGCG逆转肝癌耐多药差异基因表达

目的 探讨表没食子儿茶素没食子酸酯(EGCG)逆转人肝癌细胞耐多药的机制,为进一步在基因转录水平上高通量筛选逆转肝癌耐多药天然药物提供一定的参考依据。方法 采用人肝癌细胞Bel-7402及其耐5-氟尿嘧啶Bel-FU细胞,甲基四唑蓝法检测耐药Bel-FU细胞的耐多药性及对EGCG进行体外细胞毒性试验;选择与肝癌发生发展相关途径的42个功能基因作为检测基因,采用实时定量PCR微阵列技术检测Bel-7402组、Bel-FU组、Bel-FU+EGCG作用组基因表达;实时定量PCR检测相同条件下处理的基因Hras、MDR1表达变化以验证微阵列技术结果。结果 耐药细胞Bel-FU对5-氟尿嘧啶、阿糖胞苷、长春新碱、阿霉素、柔红霉素的耐药指数分别为:89.6、3.9、37.2、16.5、3.7;EGCG对细胞Bel-FU的IC50、IC10值分别为587.4、73.1μg/mL;实时定量PCR微阵列检测结果显示:与Be-7402组比较,Bel-FU组中有5个基因上调;与Bel-FU组比较,Bel-FU+EGCG作用组有5个基因下调,其中有3个基因为Bel-7402组与Bel-FU组之间的差异基因;实时定量PCR验证结果:Bel-FU组中基因Hras、MDR1表达为Bel-7402组中的2.84、2.74倍,与Bel-FU组比较,Bel-FU+EGCG组作用中基因Hras、MDR1表达分别下调3.21、3.74倍。结论 EGCG对人肝癌耐多药细胞Bel-FU具有一定逆转作用。     

A new stilbene glucoside gallate from the roots of Polygonum multiflorum

A new stilbenoid (1) was isolated from the root extract of Polygonum multiflorum together with eight known constituents (2∼9). The chemical structure of 1 was established as the 6″-O-monogalloyl ester of (E)-2,3,4′,5-β-tetrahydroxystilbene-2-β-D-glucopyranoside based on physicochemical and spectroscopic analyses, particularly by NMR spectroscopic data, i.e., COSY, HMQC and HMBC. Compound 1 weakly inhibited acetylcholinesterase in vitro.     

(-)-Epigallocatechin Gallate Inhibits the Pacemaker Activity of Interstitial Cells of Cajal of Mouse Small Intestine

The effects of (-)-epigallocatechin gallate (EGCG) on pacemaker activities of cultured interstitial cells of Cajal (ICC) from murine small intestine were investigated using whole-cell patch-clamp technique at 30℃ and Ca²⁺ image analysis. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. The treatment of ICC with EGCG resulted in a dose-dependent decrease in the frequency and amplitude of pacemaker currents. SQ-22536, an adenylate cyclase inhibitor, and ODQ, a guanylate cyclase inhibitor, did not inhibit the effects of EGCG. EGCG-induced effects on pacemaker currents were not inhibited by glibenclamide, an ATP-sensitive K⁺ channel blocker and TEA, a Ca²⁺-activated K⁺ channel blocker. Also, we found that EGCG inhibited the spontaneous [Ca²⁺]_i oscillations in cultured ICC. In conclusion, EGCG inhibited the pacemaker activity of ICC and reduced [Ca²⁺]_i oscillations by cAMP-, cGMP-, ATP-sensitive K+ channel-independent manner.     

培丙酯治疗缺血性心肌病疗效观察

目的 研究培丙酯对缺血性心肌病的治疗作用.方法 选择缺血性心肌病患者80例,随机分为培丙酯治疗组及5-单硝酸异山梨酯对照组.治疗2周,分别比较心功能、血液流变学、炎症指标变化情况.结果 2周后,2组患者病情均有改善,治疗组疗效更佳.结论 培丙酯治疗缺血性心肌病可以明显改善心肌缺血及心功能不全表现,疗效显著,是治疗缺血性心肌病的有效方法之一.     

没食子酸丙酯对脑缺血大鼠神经元SAPK/JNK及p38MAPK激活的抑制作用

目的探讨没食子酸丙酯对大鼠脑缺血再灌注模型缺血区周边组织神经元损伤的保护作用及其可能机制。方法通过Nissl和TUNEL染色法检测阳性神经元数量，蛋白免疫印迹、免疫组化法观察活化型Caspase-3，SAPK/JNK，p38MAPK及其磷酸化组分的表达。结果没食子酸丙酯干预后，SAPK/JNK，p-SAPK/JNK(1 h)，p38MAPK，p-p38MAPK(6 h)及活化型Caspase-3(12 h)表达均减弱，TUNEL阳性神经元减少(24 h)，Nissl阳性神经元增多(24 h)，神经元凋亡率明显降低。结论没食子酸丙酯保护缺血再灌注后神经元损伤的机制可能与抑制SAPK/JNK及p38MAPK的激活有关。     

Bioactive nutrients - Time for tolerable upper intake levels to address safety

There is increasing interest by consumers, researchers, and regulators into the roles that certain bioactive compounds, derived from plants and other natural sources, can play in health maintenance and promotion, and even prolonging a productive quality of life. Research has rapidly emerged suggesting that a wide range of compounds and mixtures in and from plants (such as fruits and vegetables, tea and cocoa) and animals (such as fish and probiotics) may exert substantial health benefits. There is interest in exploring the possibility of establishing recommended intakes or dietary guidance for certain bioactive substances to help educate consumers. A key aspect of establishing dietary guidance is the assessment of safety/toxicity of these substances. Toxicologists need to be involved in both the development of the safety framework and in the evaluation of the science to establish maximum intake/upper limits.