Effect of butylated hydroxytoluene,curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes

1.?The objective of this study was to investigate the effects of four food chemicals, namely butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG) and thiabendazole (TB), on cytochrome P450 (CYP) forms in cultured human hepatocytes.

2.?Treatment of human hepatocytes for 72 h with 2–200 µM TB produced concentration-dependent increases in CYP1A2, CYP2B6 and CYP3A4 mRNA levels, whereas treatment with BHT increased CYP2B6 and CYP3A4 mRNA levels. CYP1A2, CYP2B6 and CYP3A4 mRNA levels were induced around 48-, 21- and 9-fold, respectively, by 200 µM TB, with CYP2B6 and CYP 3A4 mRNA levels being induced around 12- and 7-fold, respectively, by 200 µM BHT.

3.?In contrast, the treatment of human hepatocytes for 72 h with PG and CC had little or no effect on CYP mRNA levels.

4.?The treatment of human hepatocytes with TB also induced CYP1A-dependent 7-ethoxyresorufin O-deethylase activity, whereas BHT induced CYP3A-dependent testosterone 6β-hydroxylase activity.

5.?In summary, the results demonstrate that TB is a mixed inducer of CYP forms in human hepatocytes inducing CYP1A, CYP2B and CYP3A forms, whereas BHT is an inducer of CYP2B and CYP3A forms.     

Role of Epigallocatechin Gallate in Glucose,Lipid, and Protein Metabolism and L-Theanine in the Metabolism-Regulatory Effects of Epigallocatechin Gallate

Epigallocatechin gallate (EGCG) and L-theanine (LTA) are important bioactive components in tea that have shown promising effects on nutrient metabolism. However, whether EGCG alone or combined with LTA can regulate the glucose, lipid, and protein metabolism of healthy rats remains unclear. Therefore, we treated healthy rats with EGCG or the combination of EGCG and LTA (EGCG+LTA) to investigate the effects of EGCG on nutrient metabolism and the role of LTA in the metabolism-regulatory effects of EGCG. The results showed that compared with the control group, EGCG activated insulin and AMP-activated protein kinase (AMPK) signals, thus regulating glucose, lipid, and protein metabolism. Compared with EGCG, EGCG+LTA enhanced hepatic and muscle glycogen levels and suppressed phosphorylation of AMPK, glycogen synthase 2, mammalian target of rapamycin, and ribosomal protein S6 kinase. In addition, EGCG+LTA inhibited the expression of liver kinase B1, insulin receptor and insulin receptor substrate, and promoted the phosphorylation level of acetyl-CoA carboxylase. Furthermore, both EGCG and EGCG+LTA were harmless for young rats. In conclusion, EGCG activated AMPK and insulin pathways, thereby promoting glycolysis, glycogen, and protein synthesis and inhibiting fatty acid (FA) and cholesterol synthesis. However, LTA cooperated with EGCG to promote glycogen metabolism and suppressed the effect EGCG on FA and protein synthesis via AMPK signals.     

表没食子儿茶素没食子酸酯对雨蛙素导致的小鼠急性胰腺炎肺损伤的作用

目的研究表没食子儿茶素没食子酸酯(EGCG)对急性胰腺炎相关性肺损伤的作用及机制。方法用随机数表法将balb/c小鼠分为3组:空白对照组腹腔注射0.9%NaC l(10 mL·kg^-1);模型组腹腔注射雨蛙素50μg·kg^-1建立小鼠急性胰腺炎肺损伤模型,这2组均每小时注射1次,共7次;实验组在造模后1,3,6 h,分别腹腔给予EGCG 25 mg·kg^-1。于造模后24 h,用脱颈法处死小鼠。眼球取血,切取肺,取胰腺,进行病理学检查;用全自动生化分析仪测定血清中淀粉酶,以硫代巴比妥酸法检测丙二醛(MDA)水平,以酶联免疫吸附法(ELISA)测定肿瘤坏死因子(TNF-α)的含量,以免疫组化SP法检测肺组织核因子(NF-κB)水平,用苏木精-尹红(HE)染色法进行肺组织学观察及组织病理学评分。结果实验组、模型组与对照组的血清淀粉酶分别为(3613.21±351.87),(4720.43±672.24),(895.41±107.18)U·L^-1;这3组的MDA分别为(13.06±0.11),(15.49±0.40),(4.26±0.69)mmol·mL^-1;这3组的TNF-ɑ分别为(59.83±14.74),(83.29±24.10),(24.76±10.24)pg·L^-1;这3组的肺组织NF-κB表达分别为0.38±0.14,0.55±0.12,0.14±0.09;这3组的肺组织病理学评分分别为(3.47±1.20),(6.54±0.51),(0.21±0.07)分;模型组与对照组比较,以上指标差异均有统计学意义(均P<0.05);实验组与模型组比较,以上指标差异均有统计学意义(均P<0.05)。结论 EGCG可通过抑制NF-κB的表达和提高对氧自由基的清除,从而减轻实验小鼠胰腺炎症相关肺组织损伤。     

表没食子儿茶素没食子酸酯对大鼠创伤性脑水肿保护作用的研究

目的：观察表没食子儿茶素没食子酸酯（EGCG）对大鼠创伤性脑损伤继发脑水肿的抑制作用及其机制。方法选择Wistar大鼠200只,按随机数字表法分为假手术组（20只）、模型组（90只）和EGCG组（90只）,采用Feeney自由落体坠击法制备大鼠创伤性脑损伤模型;EGCG组于制模后即刻腹腔注射EGCG生理盐水溶液100 mg/kg（10 mL/kg）;模型组给予等量生理盐水;均每24 h注射1次,连用2 d。于给药后24、48、72 h测定各组大鼠脑组织含水量、超氧化物歧化酶（SOD）、丙二醛（MDA）的变化,根据脑组织中伊文思蓝（EB）含量评价脑血管通透性,采用免疫组化法和蛋白质免疫印迹试验（Western Blot）测定大鼠脑组织水通道蛋白-4（AQP4）和胶质纤维酸性蛋白（GFAP）表达的变化,并观察各组大鼠脑组织病理学改变。结果与假手术组比较,模型组给药后各时间点脑组织含水量、MDA水平均明显增加,SOD水平明显降低,脑血管通透性增加;模型组制模后24 h、72 h AQP4、GFAP阳性细胞表达评分（IHC评分）均明显升高;AQP4和GFAP蛋白表达水平〔积分吸光度（IA）〕明显升高,以制模后72 h变化更显著〔脑组织含水量：（89.71±0.94）%比（78.34±0.87）%, EB的含量（μg/g）：9.13±0.66比2.71±0.72,SOD（U/mg）：63.53±12.57比130.85±9.91,MDA（nmol/mg）：10.19±1.47比4.57±0.74,AQP4 IHC评分（分）：8.81±1.75比2.76±0.82,GFAP的IHC评分（分）：9.47±1.32比6.71±0.52,AQP4蛋白表达（IA值）：1.53±0.05比0.42±0.05,GFAP蛋白表达（IA值）：1.45±0.05比0.62±0.04,均P＜0.01〕。与模型组比较,EGCG组大鼠脑组织含水量、MDA水平和AQP4、GFAP的IHC评分及蛋白表达均显著下降,SOD水平显著提高,血管通透性明显下降,以制模后72 h变化更显著〔脑组织含水量：（86.59±0.89）%, EB的含量（μg/g）：7.82±0.32,SOD（U/mg）：107.58±10.87,MDA（nmol/mg）：5.61±1.64,AQP4 IHC评分（分）：6.92±0.71,GFAP的IHC评分（分）：6.71±0.52,AQP4蛋白表达（IA值）：1.14±0.06,GFAP蛋白表达（IA值）：1.21±0.07,均P＜0.01〕;免疫组化法检测EGCG组大鼠AQP4和GFAP的阳性细胞数减少,颜色变浅。结论 EGCG对大鼠创伤性脑损伤继发脑水肿的抑制作用与降低血管通透性、增加SOD水平,降低MDA水平及AQP4和GFAP的表达有关。     

粗根老鹳草化学成分的研究

老鹳草为传统中药,有祛风湿、通经络、止泄痢的功效,其单味制剂老鹳草软膏有消炎解毒、收敛生肌的作用［１］。粗根老鹳草作为老鹳草的药材来源之一,分布较广,使用较多［２］,但其化学成分却不清楚,本文对其化学成分进行系统研究,从中分离到５个化合物,其中２个为新化合物。现报道如下：化合物Ｉ　黄色粉末,ｍｐ１１９～１２０℃。ＦＡＢＭＳ（ｍ／ｅ）：３４７（Ｍ＋１）＋,１８５（Ｍ＋１－１６２）＋,１５３。结合１ＨＮＭＲ和１３ＣＮＭＲ确定该化合物的分子组成为Ｃ１４Ｈ１８Ｏ１０,并由葡萄糖、没食子酰基、甲基组成。…     

蛇葡萄根化学成分的研究

从蛇葡萄根中分离出8种单体化合物,鉴定为β-香树脂醇、白桦脂醇、香草酸、没食子酸乙酯、山奈酚、3,5-二甲氧基-4-羟基苯甲酸、香橙素和藜芦醇,均为首次从该植物中分离得到。     

L-(-)-表没食子儿茶素没食子酸酯对二甲基胂酸促小鼠肺肿瘤发生的抑制与其抑制氧化应激

目的探讨抗氧化茶多酚L-(-)-表没食子儿茶素没食子酸酯[(-)epigallocatechin gallate,EGCG]对二甲基胂酸(dimethylarsinic acid,DMA(V))促小鼠肺肿瘤发生的抑制作用与氧化应激关系。方法利用4-硝基喹啉-1-氧化物(4-nitroquinoline 1-oxide,4NQO)作为始动剂,DMA(V)作为促进剂的致小鼠肺肿瘤两阶段动物模型。观察绿茶提取物中最有效的EGCG对DMA(V)致肿瘤发生的作用,同时通过高效液相色谱法(HPLC)测量小鼠肺中DNA氧化损伤的生物标志物8-氧-2’-脱氧鸟嘌呤核苷(8-oxo-2’-deoxyguanosine,8-oxodG)的变化。结果EGCG明显抑制4NQO与DMA(V)诱发小鼠肺肿瘤数(P<0.05)和肺组织中8-oxodG的生成(P<0.05)。结论EGCG对DMA(V)促肺肿瘤的抑制作用可能与其抑制氧化应激有关。     

没食子酸丙酯对脑缺血再灌注所致脂质过氧化损伤的保护作用

目的：研究没食子酸丙酯对脑缺血再灌注所致脂质过氧化损伤的保护作用。方法：采用结扎双侧颈总动脉及迷走神经方法,造成大鼠脑缺血９０ｍｉｎ,随后再灌注４５ｍｉｎ,结果：没食子酸丙酯能不同程度地降低脑缺血再灌注大鼠脑组织含水量和ＭＤＡ含量,提高ＳＤＯ、ＣＡＴ和ＧＳＨ－Ｐｘ活性,保护Ｎａ＾＋,Ｋ＾＋－ＡＴＰ酶活性。结论：没食子酸丙酯可通过保护脑组织抗氧的活性,抑制脂质过氧化反应,减轻自由基对脑组织的损害,对     

Epigallocatechin gallate modulates CYP450 isoforms in the female Swiss-Webster mouse.

This study was designed to determine the effect of the in vivo administration of epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on enzymes involved in the synthesis and metabolism of estradiol. EGCG (12.5, 25, or 50 mg/kg/day, i.p.) or ECG (12.5 or 25 mg/kg/day, i.p.) was administered to female Swiss-Webster mice for 7 days. The chemicals were well tolerated by the mice with the exception of EGCG given at 50 mg/kg, which resulted in severe hepatic necrosis and a 67% mortality rate. Following the administration of nontoxic doses of EGCG and ECG, aromatase (CYP19), CYP3A, CYP1A, and catechol O-methyltransferase (COMT) were measured. Additionally, the activity of CYP2E1 was determined, since this CYP450 isoform is important in the bioactivation of numerous carcinogens. The results demonstrated that ovarian aromatase activity was inhibited 56% by EGCG (25 and 12.5 mg/kg), but not ECG, while hepatic CYP3A catalytic activity and polypeptide levels were increased 31 +/- 4 and 47 +/- 2%, respectively, by 25 mg/kg of EGCG. However, ECG (but not EGCG) inhibited CYP1A catalytic activity and polypeptide levels (31 +/- 5 and 47 +/- 5%, respectively). Hepatic and renal COMT, as well as renal CYP3A remained unchanged following catechin dosing. Hepatic CYP2E1 catalytic activity and polypeptide levels were significantly increased (37 +/- 3 and 22 +/- 3%) following administration of EGCG (25 mg/kg). These results indicate that EGCG modulates enzymes responsible for both the synthesis and metabolism of estradiol, which may provide a potential mechanism for the reported action of EGCG, reported action as an inhibitor of breast tumor growth.