A high-throughput metabolomic approach to explore the regulatory effect of mangiferin on metabolic network disturbances of hyperlipidemia rats

Abstract

This paper was designed to study metabolomic characters of the high-fat diet (HFD)-induced hyperlipidemia and the intervention effects of Mangiferin (MG). In this study, we aimed to investigate the intervention of MG on rats with hyperlipidemia induced by HFD and explore the possible mechanisms of hyperlipidemia. Urine metabolic profiles were analyzed using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) coupled with the principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) models, Heatmap and metabolism pathway analysis. PCA was applied to study the trajectory of the urinary metabolic phenotype of hyperlipidemia rat after administration of MG. The VIP-plot of orthogonal PLS-DA was used for discovering potential biomarkers to clarify the mechanism of MG. Biochemical analyses indicate that MG can alleviate the hyperlipidemia damage. Twenty significantly changed metabolites (potential biomarkers) were found to be reasonable in explaining the action mechanism of MG. The effectiveness of MG on hyperlipidemia is proved using the established metabolomic method and the regulated metabolic pathways involve the TCA cycle, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine and serine and threonine metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis etc. The results indicated that MG has a favourable protective effect on HFD-induced hyperlipidemia by adjusting the metabolic disorders. It also suggests that the metabolomic technology is a powerful approach for elucidation of the action mechanisms of MG.

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“…After VOAS intervention, the level of D-glucuronic acid decreased, indicating that VOAS reversed D-glucuronic acid level. In glyoxylate and dicarboxylate metabolism, glycine is an important intermediate and glycine and glyoxylate can be mutually conversed by glutamate-glyoxylate aminotransferase [43].…”

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“…Mangiferin is protective against hyperlipidemia through the regulation of metabolic pathways such as the glyoxylate, tricarboxylic acid (TCA)and taurine cycles, as well as metabolism of dicarboxylate, glycerophospholipid, hypotaurine, and threonine, and serine, glycine, and primary bile acid biosynthesis [101]. Likewise, mangiferin enhances proteins which lead to mitochondrial biogenesis and oxidative activity such as cytochrome c oxidase subunit 6B1 (Cox6b1) and oxoglutarate dehydrogenase E1 (DHTKD1).…”

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