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Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice
- Source :
- Lipids in Health and Disease, Lipids in Health and Disease, Vol 16, Iss 1, Pp 1-14 (2017)
- Publication Year :
- 2017
- Publisher :
- BioMed Central, 2017.
-
Abstract
- Background 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). Methods 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. Results 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. Conclusion Anti-hyperlipidemia effect of SCL was confirmed by both serum biochemistry and metabolomics analysis. The mechanism may be related to the down-regulation of LXRα/SREBP-1c/FAS/ACC and SREBP2/HMGCR signaling pathways.
- Subjects :
- 0301 basic medicine
Male
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Blood lipids
030204 cardiovascular system & hematology
Mass Spectrometry
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Hyperlipidemia
lcsh:RC620-627
Schisandra
Sterol Regulatory Element Binding Proteins
Principal Component Analysis
biology
Fatty liver
lcsh:Nutritional diseases. Deficiency diseases
Fatty acid synthase
Cholesterol
Biochemistry
Metabolome
lipids (amino acids, peptides, and proteins)
Metabolic Networks and Pathways
medicine.medical_specialty
RT-PCR
Hyperlipidemias
Diet, High-Fat
Lignans
03 medical and health sciences
Schisandra chinensis lignans
Internal medicine
medicine
Metabolomics
Animals
RNA, Messenger
Liver X receptor
Triglycerides
Fatty acid metabolism
business.industry
Research
Biochemistry (medical)
medicine.disease
biology.organism_classification
Mice, Inbred C57BL
030104 developmental biology
chemistry
biology.protein
RRLC-Q-TOF-MS
business
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 1476511X
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Lipids in Health and Disease
- Accession number :
- edsair.doi.dedup.....030b4e3b37c89f10e95efe43a4cea986