Effect of a traditional Chinese medicine Liu Wei Di Huang Wan on the activities of CYP2C19, CYP2D6 and CYP3A4 in healthy volunteers

1. Liu Wei Di Huang Wan (LDW), a well-known traditional Chinese medicine, is widely used for the treatment of various diseases in China. This study was designed to investigate the potential herb–drug interactions of LDW in healthy volunteers and attempted to ascertain whether the interaction might be affected by genotypes.

2. We assessed the effect of LDW on the activities of CYP2C19, CYP2D6 and CYP3A4 in 12 Chinese healthy subjects in a single-center, controlled, non-blinded, two-way crossover clinical trial. The subject pool consisted of six extensive metabolizers with CYP2C19*1/*1 and six poor metabolizers with CYP2C19*2/*2. Placebo or 4.8?g LDW (12 pills, 0.2?g/pill, twice daily) was given to each participant for 14 continuous days with a wash-out period of 2 weeks after an oral administration of 30?mg omeprazole, 30?mg dextromethorphan hydrobromide and 7.5?mg midazolam. The activities of CYP2C19, CYP2D6 and CYP3A4 were ascertained by their respective plasma or urinary metabolic ratios on day 14 post-treatment.

3. There is no difference in the activities of the three tested enzymes before or after a 14-day administration of LDW. LDW had no effect on the pharmacokinetic parameters of the substrates and their metabolites.

4. A 14-day administration of LDW did not affect the activities of CYP2C19, CYP2D6 and CYP3A4. LDW is unlikely to cause pharmacokinetic interaction when it is combined with other medications predominantly metabolized by these enzymes.

     

Antinociceptive activity and chemical composition of Wei–Chang–An–Wan extracts

Abstract

Context: Currently, famous traditional Chinese medicine formulas have undergone re-evaluation and development in China. Wei–Chang–An–Wan (WCAW) as one of them has been used for treating various gastrointestinal diseases for several decades. The secondary development of WCAW is in progress so as to interpret the effective material basis or find new pharmacological activity.

Objective: To evaluate the antinociceptive effect of methanol extract of WCAW (ME) as well as four fractions (P.E., EtOAc, n-BuOH, H₂O) and obtain information on the correlation between the contents of the fractions and antinociceptive effect.

Materials and methods: ME was divided into four parts extracted by petroleum ether, ethyl acetate and n-butanol. Antinociceptive activity was evaluated by three models of acetic acid–induced writhing, formalin and hot-plate test in mice after repetitive administration of ME at 200, 400 or 800?mg/kg, P.E. 132?mg/kg, EtOAc 106?mg/kg, n-BuOH 176?mg/kg and H₂O 176?mg/kg for six days. The chemical compounds were analyzed by HPLC-ESI-MS.

Results: ME at 800?mg/kg inhibited acid-induced writhing by 84.69%, and reduced the licking time of second phase in formalin test by 53.23%. The inhibition rates in acid-induced writhing of P.E., EtOAc, n-BuOH and H₂O were 27.79, 33.85, 38.97 and 37.69%, respectively, and in formalin test about 50%. They had no effect on the hot-plate test. HPLC-ESI-MS analysis showed that 68 chemical compounds were detected and 41 compounds were identified from ME.

Discussion and conclusion: The results obtained herein indicate that WCAW possesses the antinociceptive activity that provides a new aspect in clinical application.     

藏药——三味檀香散药理学研究进展

三味檀香散由广枣、檀香、肉豆蔻3味药组成,是藏医及蒙医治疗心热病的常用方。对其进行深入研究具有现实的临床及开发意义。本文从药效学、药代动力学、毒理学三方面综述三味檀香散的研究进展。     

渭良伤科油手法按摩对膝关节僵硬功能康复的临床观察

目的观察渭良伤科油手法按摩对膝关节僵硬功能康复的作用。方法选取108例膝关节僵硬患者为观察对象,随机分为两组,每组各54例,实验组行渭良伤科油手法按摩,对照组单纯予手法按摩,10天为一疗程,共3个疗程。结果治疗3个疗程后,实验组患者临床显效率为92．6％,对照组临床有效率81．5％,P〈0．05,有统计学意义。结论渭良伤科油手法按比单纯手法按摩对膝关节僵硬患者关节功能康复的疗效更显著。     

卫气营血理论在成人斯蒂尔病辨证中的应用

成人斯蒂尔病临床表现复杂多样,且易反复发作,整个病程多徘徊于气、营之间,鲜有动血耗血之血分证征象。卫气营血理论根据邪气侵袭人体部位的深浅,将病程分为卫、气、营、血4个阶段。运用"卫气营血"理论辨证治疗成人斯蒂尔病,可根据其发热特点及伴随症状辨证论治,常用疏风散热、宣肺透邪法,和解少阳、透邪外出法,清气凉营、泻火解毒法,清营解毒、透热养阴法及养阴清热法。     

蒙药胃舒安对束缚-水浸应激致胃溃疡的预防作用及对TGF-β1表达的影响

[目的]评价蒙药胃舒安对束缚-水浸应激所致大鼠胃溃疡的预防作用。[方法]将Wistar实验大鼠,分正常组、给药组和对照组3组,正常组不给药,无束缚-水浸应激压力,对照组给淀粉,给药组灌胃给蒙药胃舒安,给药剂量为0．9～1．3mL／只（82．5g／L）,连续给胃舒安7d后,停食24h,建立3h束缚-水浸应激性胃溃疡模型,取胃,肉眼观察胃黏膜损伤,用Image J图像分析法测定胃黏膜溃疡面积,并进行比较。用酶联免疫吸附测定法检测胃溃疡大鼠血清转化生长因子（TGF-β1）含量并进行比较。[结果]蒙药胃舒安对3h束缚-水浸应激所致大鼠胃溃疡形成有抑制作用。胃舒安组大鼠血清TGF-β1含量明显低于对照组。[结论]蒙药胃舒安对实验大鼠束缚-水浸应激3h所致胃溃疡的形成有显著抑制作用。     

魏氏伤科治疗膝骨关节炎的经验

膝骨关节炎属于中医"痹证"的范畴,著名骨伤科流派魏氏伤科历经几代人的传承与发展,在治疗膝骨关节炎方面积累了丰富经验,强调"内外并重、气血兼顾",创立了"气血为要、筋骨并重,肝肾为重、调摄脾胃,注重手法、调护平衡"的治伤学术思想.形成了集药物内治外治、手法诊治以及导引疗法等的综合疗法.结合临床病案对魏氏伤科治疗膝骨关节炎...     

蒙药当归-4味散联合消炎痛治疗痛经疗效观察

目的：研究蒙西医治疗原发性痛经的临床疗效。方法：60例原发性痛经患者随机分为治疗组和对照组,治疗组用消炎痛联合用蒙药当归-4味散,对照组用消炎痛。结果：治疗组原发性痛经的总有效率为90%,对照组原发性痛经的总有效率为83.3%,治疗组优于对照组P<0.05。结论：经系统临床观察,蒙西医治疗原发性痛经疗效显著。     

基于药物代谢组学的中药及方剂中组分间协同增效作用

针对中药及方剂中多组分间配伍协同作用的特点,提出了利用药物代谢组学解析多组分间协同增效作用的机制的假说,并介绍了作者近期利用药物代谢组学研究方剂及组成药物相互关系的成果。     

六味地黄丸防治大鼠糖尿病肾病的实验研究

目的:观察足细胞裂孔隔膜蛋白nephrin和podocin在糖尿病肾病发病机制中的作用,探讨六味地黄丸(LWDHW)保护糖尿病肾病大鼠肾脏的机制。方法:SD大鼠腹腔注射链脲佐菌素复制糖尿病模型,1周后,按血糖浓度将成模的糖尿病大鼠随机分为:模型组(STZ,8只)、治疗组(STZ+LWDHW,8只),另设正常组(Control,8只)。治疗组给予六味地黄丸灌胃,模型组、正常组给予等量生理盐水,持续观察8周。治疗第8周末,称大鼠体重,计算肾系数,观察肾脏病理改变;检测24h尿蛋白总量、血尿素氮、血肌酐;免疫印迹检测nephrin和podocin在肾组织中的表达。结果:与正常组比较,模型组大鼠血糖,体重明显下降(P<0.01),肾系数,24h尿蛋白总量,血尿素氮,血肌酐明显升高(P<0.01);模型组大鼠肾小球肥大、毛细血管基底膜增厚,系膜基质增生,肾小管上皮细胞空泡样变,见蛋白管型;nephrin和podocin蛋白表达减少(P<0.01)。治疗组血糖、体重无明显改变;肾系数,24h尿蛋白总量,血尿素氮,血肌酐明显降低(P<0.05);病理改变明显减轻;大鼠肾组织nephrin和podocin表达明显增加(P<0.05)。结论:六味地黄丸可能通过增加足细胞nephrin和podocin表达发挥保护糖尿病肾病大鼠肾脏的作用。