Systematic investigation on the chemical basis of anti‐NAFLD Qushi Huayu Fang. Part 1: A study of metabolic profiles in vivo and in vitro by high‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry

Abstract

Qushi Huayu Fang (QHF) is a clinic-empirical prescription for treating non-alcoholic fatty liver disease (NAFLD) in China, which is composed of five herbs. However, the bioactive constituents responsible for the efficacy of QHF remain unclear. Thus, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was established and adopted to identify the constituents of QHF, and profile its metabolism in vivo and in vitro. Among the 66 constituents in QHF, only 14 compounds of six structural types were absorbed, and 34 metabolites were generated through eight metabolic pathways. A total of 20 metabolites were first reported, including four organic acids, one iridoid, two flavones, five naphthols, three anthraquinones, and five stilbenes. Glucuronidation and sulfation were the main metabolic pathways, and the intestinal metabolism played an important role in the biotransformation of QHF. Many compounds, especially those detected in the liver, the target organ of QHF, were reported to display the anti-NAFLD activity. This is the first study to explore the constituents of QHF and its metabolism in vivo and in vitro, thus realizing the first step to clarify the chemical basis of QHF qualitatively, and laying the foundation for further research on the anti-NAFLD mechanism of QHF. K E Y W O R D S HPLC-Q-TOF, intestinal bacteria, liver, metabolism, Qushi Huayu FangAbbreviations: HPLC-Q-TOF, high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry; IRE1α, inositol-requiring transmembrane kinase/endoribonuclease 1α; NAFLD, non-alcoholic fatty liver disease; Nrf-2, nuclear erythroid 2-related factor 2; PI3K, phosphatidylinositol 3-kinase; PPARα, peroxisomal proliferator-activated receptor α; QHF, Qushi Huayu Fang; SD, Sprague Dawley; SREBP-1c, sterol regulatory element-binding protein-1c; TCM, traditional Chinese medicines; TNF-α, tumor necrosis factor-α; XBP1s, X-box binding protein 1; YCHD, Yinchenhao Decoction. # Huan Liu and Zhaolin Sun contributed equally to this study.

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