Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl4-intoxicated liver injury rats. Part 1: Metabolic profiles from the liver-centric perspective

Huan Liu; Mingcang Chen; Hao Yin; Pei Hu; Yangyang Wang; Fang Liu; Xiaoting Tian; Chenggang Huang

doi:10.1016/j.jep.2019.03.044

Exploration of the hepatoprotective chemical base of an orally administered herbal formulation (YCHT) in normal and CCl₄-intoxicated liver injury rats. Part 1: Metabolic profiles from the liver-centric perspective

J Ethnopharmacol. 2019 Jun 12:237:81-91. doi: 10.1016/j.jep.2019.03.044. Epub 2019 Mar 20.

Authors

Huan Liu¹, Mingcang Chen¹, Hao Yin¹, Pei Hu¹, Yangyang Wang¹, Fang Liu¹, Xiaoting Tian², Chenggang Huang³

Affiliations

¹ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
² Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: zhghydxtxt@163.com.
³ Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: cghsimm@126.com.

PMID: 30904705
DOI: 10.1016/j.jep.2019.03.044

Abstract

Ethnopharmacological relevance: 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.

Aim of this study: 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.

Materials and methods: 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 CCl₄-induced liver injury rats.

Results: 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.

Conclusions: Sulfation and glucuronidation were the predominant biotransformations, and intestinal metabolism, prior to hepatic metabolism, occurred for most compounds. CCl₄-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.

Keywords: Carbon tetrachloride; HPLC-Q-TOF; Liver; Liver injury; Metabolites; Yin-chen-hao tang.

MeSH terms

Administration, Oral
Animals
Biotransformation
Carbon Tetrachloride
Chemical and Drug Induced Liver Injury / metabolism*
Chemical and Drug Induced Liver Injury / pathology
Drugs, Chinese Herbal / pharmacology*
Liver / drug effects
Liver / metabolism*
Liver / pathology
Male
Metabolome
Protective Agents / pharmacology*
Rats
Rats, Sprague-Dawley

Substances

Drugs, Chinese Herbal
Protective Agents
yin-chen-hao-tang
Carbon Tetrachloride