Center for Research and Development of Herbal Health Products, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
J Nat Med. 2012 Jul;66(3):468-75. doi: 10.1007/s11418-011-0607-x. Epub 2011 Nov 20.
Curcuma comosa is widely used as a traditional herbal medicine for gynecological diseases in South East Asia. Previous studies reported that it has phytoestrogenic activity, and several diarylheptanoids were found to be the active constituents. In this study, the pharmacokinetics profile and organ distribution of three active compounds of C. comosa hexane extract were investigated. Rats were separately administered C. comosa hexane extract intravenously at the dose of 125 mg/kg and orally at the doses of 125 and 250 mg/kg body weight, after which blood and target organs were collected at specified time intervals from 0 to 24 h. HPLC was used to measure the concentration of three major compounds, (6E)-1,7-diphenylhept-6-en-3-one (DPH1), (4E,6E)-1,7-diphenylhepta-4,6-dien-3-ol (DPH2), and (6E)-1,7-diphenylhept-6-en-3-ol (DPH3), which were found to be present in the blood and tissues and were subsequently used as markers. In the intravenous study, the volumes of distribution (V(d)) were 1.06, 8.57, and 6.56 L/kg and clearance values (CL(s)) were 0.28, 5.56, and 3.39 L/kg/h for DPH1, DPH2, and DPH3, respectively. After oral administration, the three major compounds of both doses reached a maximum systemic concentration at 2 h with maximum concentration (C(max)) of 0.85, 0.17, and 0.53 mg/L for the lower dose and 1.46, 0.17, and 0.61 mg/L for the higher dose. The bioavailabilities were 31.2, 24.01, and 31.56% for lower dose and 22.61, 17.66, and 17.73% for higher dose with a terminal half-life (t(1/2)) of 10.86, 6.3, and 4.62 h for lower dose and 3.85, 2.77, and 2.10 h for higher dose for DPH1, DPH2, and DPH3, respectively. These three major compounds are all found distributed in the brain, liver, kidneys, ovaries, and uterus after oral and intravenous administration and their related pharmacokinetic parameters are described. This study provides the essential pharmacokinetic data for diarylheptanoid phytoestrogenic compounds of C. comosa extract which are required for clinical dose and dosage design.
莪术在东南亚被广泛用作治疗妇科疾病的传统草药。先前的研究表明，它具有植物雌激素活性，并且发现几种二芳基庚烷类化合物是其活性成分。在这项研究中，研究了莪术正己烷提取物中三种活性化合物的药代动力学特征和器官分布。大鼠分别以 125mg/kg 的剂量静脉内给予莪术正己烷提取物，以 125 和 250mg/kg 的剂量口服给予，之后在 0 至 24 小时的指定时间间隔内从血液和靶器官中采集。使用 HPLC 测量三种主要化合物（6E）-1,7-二苯基庚-6-烯-3-酮（DPH1），（4E，6E）-1,7-二苯基庚-4,6-二烯-3-醇（DPH2）和（6E）-1,7-二苯基庚-6-烯-3-醇（DPH3）的浓度，这些化合物在血液和组织中均有发现，随后被用作标志物。在静脉内研究中，DPH1、DPH2 和 DPH3 的分布容积（V（d））分别为 1.06、8.57 和 6.56 L/kg，清除率（CL（s））分别为 0.28、5.56 和 3.39 L/kg/h。口服给药后，两种剂量的三种主要化合物均在 2 小时达到最大全身浓度，较低剂量的最大浓度（C（max））为 0.85、0.17 和 0.53mg/L，较高剂量的 C（max）为 1.46、0.17 和 0.61mg/L。较低剂量的生物利用度分别为 31.2、24.01 和 31.56%，较高剂量的生物利用度分别为 22.61、17.66 和 17.73%，DPH1、DPH2 和 DPH3 的半衰期（t（1/2））分别为 10.86、6.3 和 4.62 h 和 3.85、2.77 和 2.10 h。这三种主要化合物在口服和静脉内给药后均分布在大脑、肝脏、肾脏、卵巢和子宫中，并描述了其相关的药代动力学参数。本研究为莪术提取物中二芳基庚烷类植物雌激素化合物的临床剂量和剂量设计提供了必要的药代动力学数据。
