三羟异黄酮对正常和辐射损伤小鼠骨髓造血细胞周期的影响

目的 三羟异黄酮（genistein,GEN）对正常和辐射损伤小鼠骨髓造血细胞（bone marrow hematopoietic cell,BMHC）的细胞周期、增殖能力及bc1-2基因表达的影响,以期阐明其防护放射性造血损伤的分子机制.方法 照射前24h,GEN以160 mg/kg体重剂量给予小鼠灌胃,流式细胞仪观察BMHCs细胞周期及增殖能力变化,RT-PCR及Western blot方法分析BMHCs bcl-2 mRNA和蛋白表达情况.结果 ①GEN可诱导正常小鼠BMHCs细胞周期一过性改变,即给药后1 d,BMHCs增殖抑制,大量细胞阻滞于G0/G1期;给药后2 d,GEN诱导BMHCs由G0/G1期向S期转换,S期细胞明显增多;4d后逐渐恢复正常.②照射前24 h给药,GEN可减少射线导致的BMHCs增殖抑制,使照后阻滞于G0/G1期细胞减少;S期和G2/M期细胞增多,细胞增殖能力较强.同时,GEN预处理组bcl-2 mRNA及蛋白的表达均较高.结论 改变BMHCs细胞周期、降低BMHCs的辐射敏感性、抑制BMHCs凋亡和提高残留BMHCs的增殖分化能力可能是GEN防护放射线造血损伤的分子机制之一.     

三羟基异黄酮对卵巢去势大鼠延髓神经元保护作用的研究

目的 :观察植物雌激素三羟基异黄酮 (GST)对卵巢去势大鼠延髓神经元的保护作用。　方法 :行双侧卵巢切除术的雌性大鼠造模 ,手术 1 0天后皮下注射GST 2 0 0 μg/ (kg·d)治疗。连续给药 6周后 ,取动物脑的延髓部位检测丙二醛 (MDA)含量、超氧化物歧化酶 (SOD)活性 ,并作超薄切片电镜分析。　结果 :GST组与去卵巢对照组 (OVX组 )比较 ,MDA含量减少、SOD活性增加 (P <0 .0 1 ) ,形态学观察OVX组延髓神经元超微结构有明显的病理变化 ,而GST组能明显改善神经元的损伤 ,维持神经元结构的完整性。　结论 :GST对延髓神经元有明显的保护作用 ,其机制可能与清除氧自由基有关     

三羟基异黄酮对增生性瘢痕成纤维细胞增殖与胶原合成作用的影响

目的探讨5,7,4′-三羟基异黄酮对体外培养的人增生性瘢痕成纤维细胞增殖及胶原合成作用的影响。方法以不同浓度三羟基异黄酮处理体外培养的人增生性瘢痕成纤维细胞分为25、50、100μmol/L三组,以加DMSO溶剂为对照组,MTT法测定成纤维细胞的增殖,3H-脯氨酸掺入法测定细胞胶原合成情况,逆转录聚合酶链式反应（RT-PCR）检测Ⅰ、Ⅲ型前胶原mRNA的表达。结果三羟基异黄酮能有效抑制增生性瘢痕成纤维细胞的增殖及胶原合成（P〈0.05）,且具有剂量-效应关系;100μmol/L浓度组作用后,与对照组相比,差异有显著意义（P〈0.01）;三羟基异黄酮作用后成纤维细胞Ⅰ、Ⅲ型前胶原mRNA的表达显著下调（P〈0.05）。结论三羟基异黄酮能抑制增生性瘢痕成纤维细胞的增殖与活性,可能成为治疗瘢痕及纤维化疾病的有效药物。     

Pharmaceutical evaluation of genistein-loaded pluronic micelles for oral delivery

The purpose of the present study was to determine whether Pluronic F127 polymeric micelles could improve the oral bioavailability of a poor water-soluble drug, such as genistein. Genistein is a phytoestrogen that has estrogenic activity. F127 triblock copolymer consists of PEO100-PPO65-PEO100. Genistein was incorporated in the Pluronic F127 polymeric micelles by a solid dispersion method. The genistein release of genistein-loaded polymeric micelles was studied in vitro (in pH 1.2 and pH 6.8). And the oral bioavailabilities of genistein powder and genistein-loaded micelles were estimated at a dose of 4.0 mg/kg as genistein in rats. Drug loading amount and drug loading efficiency were 11.18% and 97.41%, respectively. The average size of the genistein-loaded polymeric micelles was 27.76 nm. And genistein release of the genistein-loaded polymeric micelles in vitro was 58% (pH 1.2) and 82% (pH 6.8). The bioavailability of genistein-loaded polymeric micelles was better than genistein powder. Consequently, Pluronic F127 polymeric micelles are an effective delivery system for the oral administration of genistein.     

染料木素对大鼠髁突软骨改建影响的初步研究

目的初步探讨染料木素对大鼠TM J髁突软骨改建的影响。方法 30只8周龄雌性大鼠,随机分为操作对照组、去势组和去势+染料木素组,去势组和去势+染料木素组大鼠行双侧卵巢切除术,术后每天给予去势+染料木素组大鼠20mg/kg的染料木素,6周后取材。HE染色观察组织形态变化,通过免疫组化和实时定量PCR分别检测Ⅱ型胶原、蛋白聚糖、ERα和ERβ的蛋白和mRNA水平变化。结果①去势组髁突软骨前部、中部厚度对显著高于操作对照组和去势+染料木素组;②去势组髁突软骨中Ⅱ型胶原及ERα、ERβ的平均阳性面积百分比显著低于操作对照组和去势+染料木素组;③去势组髁突软骨中Ⅱ型胶原、aggrecan的mRNA水平显著低于操作对照组和去势+染料木素组;④去势组髁突软骨中ERβ的mRNA水平显著低于操作对照组和去势+染料木素组,但ERα在各组之间无显著差异。结论①卵巢切除所引起大鼠髁突软骨增厚过程中新合成的软骨基质成分可能不同于正常大鼠髁突软骨;②一定剂量的染料木素可以基本恢复系统雌激素缺乏所造成的髁突软骨组织形态及软骨基质成分的改变,在此过程中染料木素可能主要通过ERβ发挥作用。     

金雀异黄素对高级蛋白氧化产物刺激大鼠系膜细胞转化生长因子β_1分泌的影响

目的观察金雀异黄素（Gen）对高级蛋白氧化产物（AOPPs）刺激下SD大鼠肾小球系膜细胞（MC）分泌TGF-β1的影响。方法以体外培养的SD大鼠MC为研究对象,分为对照组、AOPPs组和Gen组。检测细胞培养液中TGF-β1的浓度,并明确量效关系。结果AOPPs刺激的MC与对照组比较,细胞培养液中TGF-β1的浓度升高,而Gen能抑制上述效应,且具有时间和浓度依赖性。结论在体外培养条件下,Gen能抑制AOPPs刺激下MCTGF-β1表达的增加,且作用具有时间和浓度依赖性,其机制可能均与Gen灭活氧化应激有关,提示Gen对AOPPs刺激下的MC具有保护作用。     

Age decreased steady-state concentrations of genistein in plasma, liver, and skeletal muscle in Sprague-Dawley rats

Soy isoflavones are associated with low incidence of cardiovascular diseases (CVD) and hormone-dependent cancers, but no solid information is available on the relative deposition of isoflavones in the body as a function of age. One-year-old (adult) male Sprague-Dawley rats were fed control diet or one of three high-genistein isoflavone (HGI) diets at a dose of 62, 154, or 308 genistein mg/kg (ppm) diet for 5 weeks; 2-year-old (old) were fed a dose of 154 or 308 ppm. Steady-state genistein concentrations in plasma, liver, and gastrocnemius muscle of the adult rats after 12 h fast revealed a linear dose-dependent manner (P < or = 0.0001). However, there was no such relationship in the old rats. Nevertheless, old rats fed the 308 ppm genistein diet had significantly lower steady-state genistein concentrations in plasma and liver than the adult rats did (P < or = 0.05); but similar genistein concentration in muscle. The results of this study indicate that steady-state genistein concentrations in tissues of adult rats after 12 h fast exhibited a dose-dependent fashion and were diminished in specific tissues by age.     

Effect of genistein on the activities of cytochrome P450 3A and P-glycoprotein in Chinese healthy participants

1. To determine the effect of genistein on cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) function using the probe substrates midazolam and talinolol, respectively. Eighteen healthy adult male participants were enrolled in a two-phase randomized crossover design. In each phase, the participants received placebo or genistein for 14 days. On the 15th day, midazolam and talinolol were administered and blood samples were obtained. Midazolam and talinolol pharmacokinetic parameter values were calculated and compared before and after genistein administration.

2. Co-administration of genistein decreased the area under the concentration–time curve from 0 to 36?h (AUC 0-36) (143.65?±?55.40?ng h/mL versus 126.10?±?40.14?ng h/mL, p?<?0.05), and the area under the concentration–time curve from zero to infinity (AUC 0-∞) (209.18?±?56.61?ng h/mL versus 180.59?±?43.03?ng h/mL, p?<?0.05), and also maximum concentration (Cmax) of midazolam (48.86?±?20.21?ng/mL versus 36.25?±?14.35?ng/mL p?<?0.05). Similarly, AUC 0-36 (2490.282?±?668.79?ng h/mL versus 2114.46?±?861.11?ng h/mL, p?<?0.05), AUC 0-∞ (2980.45?±?921.09?ng h/mL versus 2626.92?±?1003.78?ng h/mL, p?<?0.05) and Cmax of talinolol (326.58?±?197.67?ng/mL versus 293.42?±?127.19?ng/mL, p?<?0.05) were reduced by genistein co-administration. The oral clearance of midazolam (1.68?±?0.85 h-1 versus 3.98?±?0.59 h-1, p?<?0.05) and talinolol (3.34?±?1.24 h-1 versus 3.79?±?1.55 h-1, p<0.05) were increased by genistien significantly.

3. Administration of genistein can result in a modest induction of CYP3A and possibly P-gp activity in healthy volunteers.

     

Two new isoflavone triglycosides from the small branches of Sophora japonica

Two new isoflavone triglycosides, genistein 4′-O-(6″-O-α-l-rhamnopyranosyl)-β-sophoroside (1), and genistein 4′-O-(6?-O-α-l-rhamnopyranosyl)-β-sophoroside (2), together with five known compounds, namely, sophorabioside, genistin, rutin, quercetin 3-O-β-d-glucopyranoside, and kaempferol 3-O-β-d-glucopyranoside, were isolated from the small branches of Sophora japonica L. Their structures were elucidated on the basis of spectroscopic analyses and chemical evidence.