Zhang Yuan, Ding Ting, Diao Tingting, Deng Mengjiao, Chen Suhong
Pharmazie. 2015 Jan;70(1):47-54.
Polygonum multiflorum is a traditional Chinese medicinal herb used in clinical medicine to nourish the liver and kidney. However, in recent years, there have been increased reports of clinical adverse reactions associated with Polygonum multiflorum preparations, especially due to liver injury. The cocktail method can be used to assess the influence of Polygonum multiflorum on the activity of cytochrome P450 (CYP450) isoforms CYP2B6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, and CYP2D6, which were reflected by changes in pharmacokinetic parameters in six specific probe drugs: bupropion, omeprazole, tolbutamide, phenacetin, midazolam, and metoprolol. Comprised the experimental rats were randomly divided into five groups: control group, alcohol extraction A group, alcohol extraction B group, water extraction A group, and water extraction B group. Each group five male rats and five female rats. Each of the groups received treatments by gavage as follows: control group was given normal saline, alcohol extraction A group was given 15 g/kg alcohol extract of Polygonum multiflorum (E15), alcohol extraction B group was given with 30 g/kg alcohol extract (E30), water extraction A group was given 15 g/kg water extract (W15), and water extraction B group was given 30 g/kg water extract (W30). The extract solution was orally administered once a day for 28 consecutive days. The mixture of six probe drugs was given by gavage, and blood samples were collected through the tail vein at different time points. Probe drug concentration in rat plasma was measured by liquid chromatography-mass spectrometry (LC-MS). In the treatment and control groups, Polygonum multiflorum alcoholic extract inhibited the activity of CYP2C19 and CYP2C9 and induced the activity of CYP1A2. Polygonum multiflorum aquous extract inhibited the activity of CYP2B6, CYP2C19, CYP2C9, CYP1A2, and CYP2D6. Pathological sections showed that in the alcohol extract group the liver was degenerated inconspicuously, and in the water extract group, the cytoplasm had vacuoles and particulate matter. The arrangement of liver cells was irregular.
何首乌是一种用于临床医学中滋补肝肾的传统中草药。然而，近年来，何首乌制剂临床不良反应的报道有所增加，尤其是肝损伤方面。鸡尾酒法可用于评估何首乌对细胞色素P450（CYP450）同工酶CYP2B6、CYP2C19、CYP2C9、CYP1A2、CYP3A4和CYP2D6活性的影响，这通过六种特定探针药物（安非他酮、奥美拉唑、甲苯磺丁脲、非那西丁、咪达唑仑和美托洛尔）药代动力学参数的变化得以体现。将实验大鼠随机分为五组：对照组、乙醇提取物A组、乙醇提取物B组、水提取物A组和水提取物B组。每组各有五只雄性大鼠和五只雌性大鼠。各组经口给予以下处理：对照组给予生理盐水，乙醇提取物A组给予15 g/kg何首乌乙醇提取物（E15），乙醇提取物B组给予30 g/kg乙醇提取物（E30），水提取物A组给予15 g/kg水提取物（W15），水提取物B组给予30 g/kg水提取物（W30）。提取物溶液每天经口给药一次，连续给药28天。通过灌胃给予六种探针药物的混合物，并在不同时间点通过尾静脉采集血样。采用液相色谱-质谱联用（LC-MS）法测定大鼠血浆中探针药物浓度。在治疗组和对照组中，何首乌乙醇提取物抑制了CYP2C19和CYP2C9的活性，并诱导了CYP1A2的活性。何首乌水提取物抑制了CYP2B6、CYP2C19、CYP2C9、CYP1A2和CYP2D6的活性。病理切片显示，乙醇提取物组肝脏退变不明显，而水提取物组细胞质有液泡和颗粒物质。肝细胞排列不规则。
