Metabolomics study of the therapeutic mechanism of Schisandra Chinensis lignans in diet-induced hyperlipidemia mice - PubMed (original) (raw)

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

Jing-Hui Sun et al. Lipids Health Dis. 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.

Keywords: Hyperlipidemia; Metabolomics; RRLC-Q-TOF-MS; RT-PCR; Schisandra chinensis lignans.

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Conflict of interest statement

The animal study proposal was approved by the Institutional Animal Care and Use Committee (IACUC) of Beihua University with the permit number: CPBHU IACUC2015–007.

Not applicable.

Competing interests

The authors declare that have no competing interests.

Figures

Fig. 1

Fig. 1

Comparison on serum TC and TG contents between control and model groups (x¯±s, n = 24). Note: CON: control group; MOD: model group. *: Compared with those in the control group, P < 0.01

Fig. 2

Fig. 2

Comparison on serum TC, TG, LDL-c and HDL-c contents between groups (x¯±s, n = 12). Note: CON: control group; CON + SCL: control + SCL group; MOD: model group; MOD + SCL: model + SCL group. *: compared with those in the control group, P < 0.05, **: P < 0.01; #: compared with those in the model group, P < 0.05, ##: P < 0.01

Fig. 3

Fig. 3

Base peak intensity (BPI) chromatograms obtained from the negative and positive ion RRLC-Q-TOF-MS analyses of control, model and model + SCL mouse

Fig. 4

Fig. 4

3D–PCA score plots of control and model group (formula image: control group; formula image: model group)in negative (a) and positive (b) ion mode; loading plots from the result of PCA of control and model group in negative (c) and positive (d) ion mode

Fig. 5

Fig. 5

3D–PCA score plots of model and SCL group (formula image: model group; formula image: model + SCL group)in negative (a) and positive (b) ion mode; loading plots from the result of PCA of model and model + SCL group in negative (c) and positive (d) ion mode

Fig. 6

Fig. 6

Comparison of the relative intensity of potential biomarkers in control, model and model + SCL group. Note: Values are expressed as mean ± standard deviation (SD). *: P < 0.05 and **: P < 0.01 compared with the control group; #: P < 0.05 compared with the model group

Fig. 7

Fig. 7

Effects of SCL on the mRNA expression of lipid synthesis and its related genes. Note: *: P < 0.05 compared with those in the control group; #: P < 0.05 compared with those in the model group

Fig. 8

Fig. 8

Effects of SCL on the mRNA expression of cholesteral synthesis and its related genes. Note: *: P < 0.05 compared with the control group; #: P < 0.05 compared with those in the model group

Fig. 9

Fig. 9

Potential metabolic pathways disturbed in hyperglycemia mice induced by HFD and alterations by SCL treatment. Notes: “formula image” and “formula image” in blue indicate that in HFD model group up- and down-regulated compared with the control group; “formula image” and “formula image” in red indicate that in model + SCL group up- and down-regulated compared with the HFD model group

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