Metabolomic analysis identifies the regulation of lipid metabolism pathway as potential mechanisms of Jiangzhi decoction against non-alcoholic fatty liver disease

J Pharm Pharmacol. 2023 Oct 5;75(10):1366-1377. doi: 10.1093/jpp/rgad067.

Abstract

Objectives: To illustrate the metabolic regulatory mechanisms of Jiangzhi decoction (JZD) against non-alcoholic fatty liver disease (NAFLD).

Methods: High-fat diet (HFD)-induced NAFLD rats were treated with JZD. The pathological morphology, lipid indexes and liver function were detected. Metabolic profiles were examined by liquid chromatography-mass spectrometry (LC-MS). Multivariate and univariate statistical analysis were used to search the differential metabolites. Pathway enrichment analysis was carried out using Kyoto Encyclopedia of Genes and Genomes database. Compound-gene networks were built by Cytoscape software.

Results: JZD significantly alleviated the pathological conditions and improved lipid index levels. Multivariate analysis showed a good separation among different groups. Three hundred and twenty-seven metabolites in HFD versus control and 301 metabolites in JZD versus HFD were identified to be significantly different. Pathway enrichment analysis showed that lipid metabolism pathways were prominent altered pathways. Importantly, the relationships were more distant between JZD and HFD groups in all five lipid metabolism pathways, including arachidonic acid metabolism, linoleic acid metabolism, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism and sphingolipid metabolism, while those were obviously closer between JZD and control groups. Simultaneously, JZD treatment restored the levels of disturbed differential metabolites in HFD group.

Conclusion: JZD had an effect on alleviating NAFLD via regulating relevant lipid metabolism.

Keywords: Jiangzhi decoction (JZD); lipid metabolism; metabolomics; non-alcoholic fatty liver disease (NAFLD).