银杏叶提取物对三氯乙烯诱导的人角质形成细胞凋亡的影响

目的研究体外培养条件下银杏叶提取物(ginkgo biloba leaf extracts,EGb)对三氯乙烯(trichloroethylene,TCE)诱导的正常人表皮角质形成细胞(normal human epidernis keratinocyte,NHEK)凋亡的影响。方法体外培养条件下,用中性红吸附试验(NRU)测定TCE对NHEK的中性红吸附减少50%的质量浓度(NR50值)和EGb的最低有效保护质量浓度。用透射电子显微镜(transmission electron microscope,TEM)观察细胞凋亡形态学改变,流式细胞仪(flow cytometer,FCM)测定细胞DNA含量并计算凋亡发生率。结果TCE对NHEK的NR50值为4.53(3.92~5.13)mmol/L;用10、50、100、150和200 mg/L EGb预孵育NHEK 2 h时,由2.0 mmol/L TCE引起的细胞活力的下降随EGb剂量的增加逐渐恢复,且150 mg/L为最低有效保护剂量。TCE可引起NHEK的超微结构呈凋亡改变,凋亡发生率呈剂量依赖式增加。与0.125、0.5和2.0 mmol/LTCE暴露组相比,150 mg/L EGb预孵育组,细胞超微结构恢复到正常对照组水平,凋亡发生率明显减少。结论体外培养条件下,EGb可以抑制TCE诱导的NHEK的细胞凋亡。     

银杏叶提取物的胃粘膜保护作用(英文)

目的:研究银杏叶提取物的胃粘膜保护作用.方法:采用大鼠束缚-冷冻应激(RCS)模型和小鼠无水乙醇损伤模型观察GbE对胃粘膜损伤指数的影响;采用幽门结扎法收集胃液,观察GbE对胃液分泌量,胃液酸度和胃蛋白酶活性的影响;采用硫代巴比妥酸(TBA)法测定胃粘膜及血清中丙二醛(MDA)含量.结果:GbE(25,50,100 mg/kg,bid×5 d,ig)剂量依赖性地抑制RCS和无水乙醇引起的胃粘膜损伤.用药组应激后的胃粘膜损伤指数分别为对照组的58％,43％和31％;用药组乙醇诱发的胃粘膜损伤指数降至对照组的62％,36％和26％;GbE尚能增强西米替丁对胃粘膜的保护作用,但对大鼠胃液分泌量、胃液酸度及胃蛋白酶活性GbE并无明显影响.小鼠经无水乙醇ig后1 h,胃粘膜和血清中的MDA含量显著升高(P<0.01),而GbE(25,50,100 mg/kg,ig)预处理则可以明显抑制MDA的升高.结论:GbE具有胃粘膜保护作用,并且与西米替丁在治疗急性胃粘膜损伤方面具有协同作用.     

银杏叶提取物对脑缺血再灌注大鼠的保护作用

目的探讨银杏叶提取物(GbE)对缺血性脑卒中神经元保护作用机制。方法SD大鼠60只随机分为假手术组、再灌注组及银杏叶组。脑缺血再灌注损伤模型以脑中动脉建立。银杏叶组在术前给予口服GbE,再灌注组给予生理盐水,用免疫组化染色检测海马CA1区凋亡细胞数。结果再灌注组各时段的细胞凋亡数明显高于假手术组(P<0.05),银杏叶组各时段的细胞凋亡数明显低于再灌注组(P<0.05)。结论银杏叶可能对海马神经元有保护作用。     

Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers

AIMS

To assess the effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers.

METHODS

Fourteen healthy male volunteers (age range 19–25 years) received orally administered bupropion (150 mg) alone and during treatment with G. biloba 240 mg day⁻¹ (two 60-mg capsules taken twice daily) for 14 days. Serial blood samples were obtained over 72 h after each bupropion dose, and used to derive pharmacokinetic parameters of bupropion and its CYP2B6-catalysed metabolite, hydroxybupropion.

RESULTS

Ginkgo biloba extract administration resulted in no significant effects on the AUC_0–∞ of bupropion and hydroxybupropion. Bupropion mean AUC_0–∞ value was 1.4 µg·h ml⁻¹[95% confidence interval (CI) 1.2, 1.6] prior to G. biloba treatment and 1.2 µg·h ml⁻¹ (95% CI 1.1, 1.4) after 14 days of treatment. Hydroxybupropion mean AUC_0–∞ value was 8.2 µg·h ml⁻¹ (95% CI 6.5, 10.4) before G. biloba administration and 8.7 µg·h ml⁻¹ (95% CI 7.1, 10.6) after treatment. The C_max of hydroxybupropion increased from 221.8 ng ml⁻¹ (95% CI 176.6, 278.6) to 272.7 ng ml⁻¹ (95% CI 215.0, 345.8) (P = 0.038) and the t_1/2 of hydroxybupropion fell from 25.0 h (95% CI 22.7, 27.5) to 21.9 h (95% CI 19.9, 24.1) (P = 0.000).

CONCLUSIONS

Ginkgo biloba extract administration for 14 days does not significantly alter the basic pharmacokinetic parameters of bupropion in healthy volunteers. Although G. biloba extract treatment appears to reduce significantly the t_1/2 and increase the C_max of hydroxybupropion, no bupropion dose adjustments appear warranted when the drug is administered orally with G. biloba extract, due to the lack of significant change observed in AUC for either bupropion or hydroxybupropion.     

银杏叶提取物的免疫调节作用研究进展

银杏叶提取物是一种具有广泛生物学功能的活性物质。该文从免疫器官重量、单核巨噬细胞与自然杀伤细胞、体液免疫、细胞免疫、细胞因子以及红细胞免疫、粘膜免疫等方面综述了银杏叶提取物的免疫调节作用。     

银杏叶提取物对CYP酶的影响及与其他药物的相互作用

综述了近年来银杏叶提取物(Ginkgo biloba extract)与其他药物相互作用的研究进展。研究表明银杏叶提取物在大鼠体内和人体内外对CYP酶的影响不一致。人体内银杏叶提取物对药物代谢酶CYP 2C19和CYP 2E1有诱导作用,分别增强了美芬妥因、奥美拉唑和氯唑沙宗的代谢。银杏叶提取物通过降低血中超氧化物歧化酶水平而发挥抗氧化作用,提高了抗精神病药物的疗效。银杏叶提取物还可能与阿司匹林、华法林和曲唑酮等发生药效学方面的相互作用,在临床应用中要引起重视。因此,需要进一步在人体内研究银杏叶提取物与其他药物的相互作用。     

Effect of an extract of Ginkgo biloba on rat brain energy metabolism in hypoxia

Summary The purpose of the present investigation was to determine brain energy metabolism under hypoxic conditions as influenced by an extract of Ginkgo biloba (EGB). Male Sprague-Dawley rats treated with EGB were exposed to hypobaric or hypoxic hypoxia, and at various time points during or after hypoxia the levels of high-energy phosphates and some substrates of glycolysis were measured in brain cortical tissue. Rats treated with EGB (100 mg/kg, intraperitoneally) survived hypobaric hypoxia for a much longer period than controls (e.g. controls: 3.9±1.8 min, EGB-treated: 23.6±10.5 min). The brain glucose level was elevated by EGB in most experimental series, and the lactate concentration was slightly lower than in control brains. The lowering of lactate/pyruvate ratio was due to the decreased level of lactate and to the enhanced concentration of pyruvate as well. When hypoxia was sufficiently severe the breakdown of high-energy phosphates was less pronounced in EGB-treated animals. After oral application of EGB for 14 days the rats survived hypobaric hypoxia for 25.7± 2.5 min whereas controls survived for 11.5±5.1 min. However, brain energy metabolism was not significantly influenced by this oral treatment. It is suggested that changes in brain energy metabolism and blood flow may contribute to the protective effect of EGB against hypoxia.     

银杏叶提取物用于治疗神经系统疾病的研究进展

目的：为进一步研究银杏叶提取物用于治疗神经系统疾病提供参考。方法：查阅近年来国内外有关银杏叶提取物治疗神经系统疾病的文献,对研究结果及作用机制进行分析。结果：银杏叶提取物治疗急性脑梗死、蛛网膜下腔出血、帕金森病和周围神经病时具有清除氧自由基、抗血小板和扩张脑部血管等作用且不良反应少,但对阿尔茨海默病的治疗价值尚存争议。结论：银杏叶提取物治疗多种神经系统疾病的效果较好,但用于阿尔茨海默病治疗尚需进一步研究。     

Effect of Ginkgo biloba extract on lopinavir,midazolam and fexofenadine pharmacokinetics in healthy subjects

ABSTRACT

Objective: Animal and in vitro data suggest that Ginkgo biloba extract (GBE) may modulate CYP3A4 activity. As such, GBE may alter the exposure of HIV protease inhibitors metabolized by CYP3A4. It is also possible that GBE could alter protease inhibitor pharmacokinetics (PK) secondary to modulation of P-glycoprotein (P?gp). The primary objective of the study was to evaluate the effect of GBE on the exposure of lopinavir in healthy volunteers administered lopinavir/ritonavir. Secondary objectives were to compare ritonavir exposure pre- and post-GBE, and assess the effect of GBE on single doses of probe drugs midazolam and fexofenadine.

Methods: This open-label study evaluated the effect of 2 weeks of standardized GBE administration on the steady-state exposure of lopinavir and ritonavir in 14 healthy volunteers administered lopinavir/ritonavir to steady-state. In addition, single oral doses of probe drugs midazolam and fexofenadine were administered prior to and after 4 weeks of GBE (following washout of lopinavir/ritonavir) to assess the influence of GBE on CYP3A and P?gp activity, respectively.

Results: Lopinavir, ritonavir and fexofenadine exposures were not significantly affected by GBE administration. However, GBE decreased midazolam AUC_0–∞ and C_max by 34% (?p = 0.03) and 31% (?p = 0.03), respectively, relative to baseline. In general, lopinavir/ritonavir and GBE were well tolerated. Abnormal laboratory results included mild elevations in hepatic enzymes, cholesterol and triglycerides, and mild-to-moderate increases in total bilirubin.

Conclusions: Our results suggest that GBE induces CYP3A metabolism, as assessed by a decrease in midazolam concentrations. However, there was no change in the exposure of lopinavir, likely due to ritonavir's potent inhibition of CYP3A4. Thus, GBE appears unlikely to reduce the exposure of ritonavir-boosted protease inhibitors, while concentrations of unboosted protease inhibitors may be affected. Limitations to our study include the single sequence design and the evaluation of a ritonavir-boosted protease inhibitor exclusively.