Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice

• Published in: Lipids in health and disease 2017-08, Vol.16 (1), p.145-145, Article 145
• Main Authors: Sun, Jing-Hui, Liu, Xu, Cong, Li-Xin, Li, He, Zhang, Cheng-Yi, Chen, Jian-Guang, Wang, Chun-Mei
• Format: Article
• Language: English
• Subjects: Acetyl-CoA carboxylase; Analysis; Animals; Biochemistry; Biomarkers - blood; Cardiovascular disease; Care and treatment; Cholesterol; Cholesterol - blood; Choline; Chromatography; Coenzyme A; Diet; Diet, High-Fat - adverse effects; Down-regulation; Fatty acids; Fatty liver; Fatty-acid synthase; Feeds; Gene expression; Genomes; Health aspects; Hepatology; High density lipoprotein; High fat diet; High performance liquid chromatography; Hydroxymethylglutaryl-CoA reductase; Hyperlipidemia; Hyperlipidemias - blood; Hyperlipidemias - drug therapy; Hyperlipidemias - genetics; Inflammation; Insulin resistance; Lignans - therapeutic use; Limited liability companies; Lipid metabolism; Lipids; Lipogenesis; Lipoproteins; Liquid chromatography; Liver diseases; Liver X receptors; Low density lipoprotein; Male; Mass Spectrometry; Mass spectroscopy; Metabolic Networks and Pathways - genetics; Metabolic pathways; Metabolism; Metabolites; Metabolome; Metabolomics; Mice, Inbred C57BL; NMR; Nuclear magnetic resonance; Physiological aspects; Polymerase chain reaction; Principal Component Analysis; Proteins; R&D; Research & development; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; RRLC-Q-TOF-MS; RT-PCR; Schisandra; Schisandra - chemistry; Schisandra chinensis lignans; Sterol Regulatory Element Binding Proteins - genetics; Sterol Regulatory Element Binding Proteins - metabolism; Sterols; Studies; Tricarboxylic acid cycle; Triglycerides - blood
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-017-0533-3

Schisandra, a globally distributed plant, has been widely applied for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China. In the present work, a rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics was conducted to investigate the intervention effect of Schisandra chinensis lignans (SCL) on hyperlipidemia mice induced by high-fat diet (HFD). Hyperlipidemia mice were orally administered with SCL (100 mg/kg) once a day for 4 weeks. Serum biochemistry assay of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) was conducted to confirm the treatment of SCL on lipid regulation. Metabolomics analysis on serum samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of liver lipid metabolism, sterol regulatory element-binding proteins (SREBPs) and its related gene expressions were measured by quantitative real-time polymerase chain reaction (RT-PCR) for investigating the underlying mechanism. Oral administration of SCL significantly decreased the serum levels of TC, TG and LDL-c and increased the serum level of HDL-c in the hyperlipidemia mice, and no effect of SCL on blood lipid levels was observed in control mice. Serum samples were scattered in the PCA scores plots in response to the control, HFD and SCL group. Totally, thirteen biomarkers were identified and nine of them were recovered to the normal levels after SCL treatment. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, the anti-hyperlipidemia mechanisms of SCL may be involved in the following metabolic pathways: tricarboxylic acid (TCA) cycle, synthesis of ketone body and cholesterol, choline metabolism and fatty acid metabolism. Meanwhile, SCL significantly inhibited the mRNA expression level of hepatic lipogenesis genes such as SREBP-1c, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC), and decreased the mRNA expression of liver X receptor α (LXRα). Moreover, SCL also significantly decreased the expression level of SREBP-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in the liver of hyperlipidemia mice. Anti-hyperlipidemia effect of SCL was confirmed by