Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changlexi Street, Xi'an 710032, China.
Department of Pharmacy, 455 Hospital of PLA, Shanghai 200052, China.
Phytomedicine. 2019 Mar 15;56:64-73. doi: 10.1016/j.phymed.2018.09.239. Epub 2018 Oct 11.
Acacia catechu (L.f.) Willd (ACW) and Scutellaria baicalensis Georgi (SBG) are two famous herbs and often used in many traditional Chinese compound prescriptions. In clinical practice, ACW-SBG couple as a famous traditional herb couple, was widely used for treating infantile cough, phlegm and fever which caused by pulmonary infection. Meanwhile, a standardized bioflavonoid composition-UP446 with ACW extract and SBG extract has been used in both special nutritional products and joint care dietary supplements. However, its herb-herb interactions based on absorption, distribution, metabolism and excretion (ADME) study had not been investigated.
The aim of this study was to evaluate potential pharmacokinetic, tissue distribution and excretion interactions between ACW and SBG, and to provide useful information for the development of suitable dosage forms and clinical applications.
A sensitive and reliable LC-MS/MS method was established to the quantification of four major bioactive components in rat biological samples. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. Based on this, we obtained and compared the parameters about pharmacokinetics, tissue distribution and excretion of four major bioactive components in this study.
This work revealed that the parameters including plasma pharmacokinetics, tissue distribution and excretion of (+)-catechin (C), (-)-epicatechin (EC), baicalin (BL) and baicalein (BLE) in single administration had significant differences compared co-administration. The results illustrated that interactions between two herbs are related to the effect of competitive gastrointestinal absorption inhibition and drug metabolism by liver metabolic enzymes. Moreover, the alteration of C and EC in the tissue of lung maybe could enhance the pharmacological activity for treating pulmonary infection.
This is the first report to evaluate the pharmacokinetics, tissue distribution and excretion of co-administration of ACW or SBG to rats and compared its properties of four major bioactive components. The results demonstrate that herb -herb interactions occurred in this herb couple.
金合欢（L.f.）威尔德（ACW）和黄芩（SBG）是两种著名的草药，常用于许多中药复方制剂。在临床实践中，ACW-SBG 作为一种著名的传统草药组合，被广泛用于治疗由肺部感染引起的小儿咳嗽、痰热等。同时，一种标准化的生物类黄酮组合物 UP446 已用于特殊营养产品和关节保健膳食补充剂，其由 ACW 提取物和 SBG 提取物组成。然而，其基于吸收、分布、代谢和排泄（ADME）的草药相互作用研究尚未得到研究。
本研究旨在评价 ACW 和 SBG 之间潜在的药代动力学、组织分布和排泄相互作用，为开发合适的剂型和临床应用提供有用的信息。
建立了一种灵敏、可靠的 LC-MS/MS 方法，用于定量测定大鼠生物样品中的四种主要生物活性成分。该方法经过准确度、精密度、线性、范围、选择性、定量下限（LLOQ）、回收率和基质效应的验证，均符合法规指南的验收标准。在此基础上，我们获得并比较了本研究中四种主要生物活性成分的药代动力学、组织分布和排泄参数。
本工作表明，与单次给药相比，（+）-儿茶素（C）、（-）-表儿茶素（EC）、黄芩苷（BL）和黄芩素（BLE）的血浆药代动力学、组织分布和排泄参数均有显著差异。结果表明，两种草药之间的相互作用与竞争性胃肠道吸收抑制和肝脏代谢酶对药物代谢的影响有关。此外，肺组织中 C 和 EC 的变化可能增强其治疗肺部感染的药理活性。
这是首次评价 ACW 或 SBG 联合给药后大鼠体内药代动力学、组织分布和排泄的相互作用，并比较了其四种主要生物活性成分的性质。结果表明，该草药组合存在草药相互作用。
