Uncovering the Treatment of Metabolic Syndrome Effects and Mechanisms of Triterpenoids in Alismatis Rhizoma Based on Metabolomics and Lipidomics

Abstract

Ethnopharmacological relevance: Alismatis Rhizoma is a traditional Chinese medicine that has been used since ancient times, which has been recorded in Jin Gui Yao Lue and Compendium of Materia Medica. Its traditional efficacy mainly includes diuretic and hypolipidemic therapy, suggesting its application prospect for lipid-lowering function. Modern pharmacological studies have demonstrated its protective activity against fatty liver injury that is caused by alcohol or high-fat diet. However, the effect and mechanism of Alismatis Rhizoma extract on treating nonalcoholic fatty liver disease and metabolic syndrome induced by high-fructose drink remains unclear.

Aim of the study: To investigate the therapeutic effect and mechanism of triterpenes from Alismatis Rhizoma on high fructose-induced metabolic syndrome in mice.Material/methods: Triterpenoid’s ingredients of Alismatis Rhizoma extract were detected through UHPLC/Q-Orbitrap-MS. The protection ofAlismatis Rhizoma extract on high fructose-induced metabolic syndrome was evaluated from serum, liver biochemical indicators and liver pathological sections. Hepatic metabolomics by ¹H-NMR and lipidomics by UHPLC/Q-Orbitrap-MS are aimed at screening potential biomarkers.

Results: The chemical components in Alismatis Rhizoma extract were quickly separated and characterized by UHPLC/Q-Orbitrap and 31 triterpenoids were preliminary identified. The results of serum biochemical analysis showed that the levels of TG, TC, LDL-C, and UA after the pioglitazone and Alismatis Rhizoma extract treatment were markedly decreased. A total of 52 endogenous metabolites were identified by metabolomics from liver tissues and 32 differential metabolic markers associated with high fructose-induced metabolic syndrome were screened out, which is mainly correlated to the eight metabolic pathways. Lipidomics analysis of liver suggested that a total of 53 differential lipids were screened out from Alismatis Rhizoma after treatment, of which 17 lipids were up-regulated and 36 lipids were down-regulated, which was mainly treated through reducing the synthesis of glycerophosphate and ceramide and improving the secretion of bile acid to treat high fructose-induced metabolic syndrome.

Conclusions: This study shows that triterpenes extracted from Alismatis Rhizoma can treat metabolic syndrome mainly by inhibiting energy metabolism, amino acid metabolism and regulating bile acid to reduce phospholipid content.

Note:
Funding Information: This work was supported by the National Key Research and Development Plan of China (No. 2018YFC1707904), and Tianjin Committee of Science and Technology, China (21ZYJDJC00080).

Declaration of Interests: There is no conflict of interest or financial interests among the authors in this study.

Ethics Approval Statement: All protocols used in this study followed National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (Ethics approval number TCM-LAEC2020019).

Keywords: Metabolic syndrome, Alismatis Rhizoma extract, fructose, metabolomics, lipidomics