Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
J Ethnopharmacol. 2019 Jun 12;237:81-91. doi: 10.1016/j.jep.2019.03.044. Epub 2019 Mar 20.
Yin-Chen-Hao Tang (YCHT), derived from "Treatise on Febrile Diseases" in ancient China, has been a very popular hepatoprotective three-herb formula in China and Japan, although its chemical base remains unclear.
As the first step in revealing the hepatoprotective chemical base of YCHT, we aimed to clarify the absorbed ingredients and associated metabolic pathways for orally dosed YCHT in both normal and liver injury rats from a liver-centric perspective.
With the aid of 10 reference compounds, the absorbed ingredients and generated metabolites were systematically characterized by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF) in the portal vein plasma (the plasma before hepatic disposition) - liver - systemic plasma (the plasma after hepatic disposition), following oral administration of YCHT in normal and CCl-induced liver injury rats.
A total of 38 compounds with six chemical structures, consisting of 10 prototypes and 28 metabolites generated through 9 biotransformations, were absolutely or tentatively identified, and 25 compounds were first reported on YCHT treatments. Among them, 8 compounds were absolutely confirmed by comparing with standard substances, and some had published hepatoprotective activities. Compared with the 35, 15, and 29 compounds identified in the portal vein plasma, liver, and systemic plasma of normal rats, respectively, the corresponding numbers of characterized compounds were 37, 13 and 29 in the liver injury rats.
Sulfation and glucuronidation were the predominant biotransformations, and intestinal metabolism, prior to hepatic metabolism, occurred for most compounds. CCl-induced liver injury caused only slight changes in the metabolic profiles of rats orally administered YCHT. These results provided the precondition for further quantitative analysis and pharmacodynamic screening of compounds in YCHT.
茵陈蒿汤（YCHT）源自中国古代的《伤寒论》，是中、日两国非常流行的一种护肝三味药方剂，但其化学基础仍不清楚。
作为揭示 YCHT 护肝化学基础的第一步，我们旨在从肝脏角度阐明正常和肝损伤大鼠口服 YCHT 的吸收成分及其相关代谢途径。
借助 10 种对照化合物，通过高效液相色谱-四极杆飞行时间质谱联用（HPLC-Q-TOF），在正常和 CCl4 诱导的肝损伤大鼠口服 YCHT 后，于门静脉血浆（肝脏处置前的血浆）-肝脏-系统血浆（肝脏处置后的血浆）中系统地对吸收成分和生成代谢物进行了表征。
共鉴定出 38 种化合物，其中 6 种化学结构，包括 10 种原型和 28 种通过 9 种生物转化生成的代谢物，并绝对或推测鉴定出 25 种化合物在 YCHT 治疗中首次报道。其中，8 种化合物通过与标准物质比较得到绝对确认，其中一些具有已发表的护肝活性。与正常大鼠门静脉血浆、肝脏和系统血浆中分别鉴定出的 35、15 和 29 种化合物相比，肝损伤大鼠中鉴定出的相应化合物数分别为 37、13 和 29。
硫酸化和葡萄糖醛酸化是主要的生物转化，大多数化合物在进入肝脏代谢之前先在肠道中代谢。CCl4 诱导的肝损伤仅使口服 YCHT 的大鼠代谢谱发生轻微变化。这些结果为进一步对 YCHT 中化合物进行定量分析和药效筛选提供了前提条件。
