Metabonomics Reveals that Aristolochic Acid I Affects β-oxidation of Fatty Acids, Glucose Metabolism and the TCA Cycle in the Mice Liver

Abstract

Abstract: Objective To reveal the differential endogenous substances generated via hepatic metabolism stimulated by aristolochic acid I and the most relevant metabolic pathways using metabonomics combined with molecular biotechnology. Furthermore, to systematically explore the mechanism by which aristolochic acid I affects hepatic metabolic functions in mice. Methods Six-week-old male C57BL/6 mice were randomly divided into four groups of different doses of aristolochic acid I: 0.2, 2, 10 and 20 mg·kg^-1, and one untreated control group. The drug was administrated by gavage, 5 days/week for 4 consecutive weeks. Metabonomics technology combined with physiology, pathology, molecular biology, enzymology, drug metabolism and systems biology were used to explore the mechanism by which aristolochic acid I affects hepatic metabolic functions in mice. Results Aristolochic acid I affected hepatic metabolism by promoting glycolysis in hepatocytes, improving the fatty acid uptake function of hepatocytes, inhibiting gluconeogenesis and β oxidation of fatty acid, impeding the TCA cycle, and finally leading to hepatic microenvironment metabolic disorder. Conclusion Based on metabonomics combined with bioinformatics, the mechanism by which aristolochic acid I affected hepatic metabolic functions was illuminated from a new perspective.

Key words: aristolochic acid I, metabonomics, metabolic pathway, mitochondrion, TCA cycle

CLC Number:

R965

CUI Yuan, LI Haishan, SONG Naining, LI Bin, SUI Feng, LI Yingfei, GUO Jiabin, JIA Qiang, LI Hua, GAO Yue, SHEN Guolin. Metabonomics Reveals that Aristolochic Acid I Affects β-oxidation of Fatty Acids, Glucose Metabolism and the TCA Cycle in the Mice Liver[J]. Chinese Journal of Pharmacovigilance, 2019, 16(8): 449-466.

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