Inonotus obliquus polysaccharide ameliorates serum profiling in STZ-induced diabetic mice model

Abstract

Background: Diabetes mellitus is a systemic disease mainly caused by the disorder of metabolism, which has become huge threat to human health. Polysaccharides are the main active substance from Inonotus obliquus (I. obliquus) with hypoglycemic effect. This study aims to evaluate the hypoglycemic activity and investigate the molecular mechanism of I. obliquus polysaccharide (IOP) in streptozotocin (STZ)-induced diabetic mice using metabolomics based on UPLC-Q-Exactive-MS method.

Results: The results showed that the oral administration of IOP in high dose (1.2 g/kg) can significantly reduce the blood glucose with 31% reduction comparing with the diabetic model and relieve dyslipidemia in diabetic mice. By UPLC-Q-Exactive-MS method and multivariate statistical analysis, a total of 15 differential metabolites were identified, including 4 up-regulated and 11 down-regulated biomarkers, of which L-tryptophan, L-leucine, uric acid, 12-HETE, arachidonic acid, PC(20:1(11Z)/14:1(9Z)) and SM(d18:0/24:1(15Z)) were exhibited an important variation, as the potential biomarkers in diabetes. Pathway analysis indicated that phenylalanine, tyrosine and tryptophan biosynthesis and arachidonic acid metabolism were prone to interference in diabetes. Moreover, leucine and proline were reversed and phytosphingosine was further reduced in diabetic mice under the intervention of IOP.

Conclusion: IOP has predominant hyperglycemic effect on STZ-induced diabetic mice via ameliorating serum profiling.

Keywords: Diabetes; Hypoglycemic effect; Inonotus obliquus polysaccharide; Metabolomics; Molecular mechanism.

Fig. 1

Effects of IOP on oral glucose tolerance test a at 0, 30, 60, 90, 120 min and area under curve b in the experimental mice

Fig. 2

The PCA score plot of serum samples from C (control group), M (model group), and H (IOPH group)

Fig. 3

OPLS-DA score plot of serum samples from C (control group) and M (model group)

Fig. 4

A heat map demonstrating the trend of metabolites variation in C (control group) and M (model group)

Fig. 5

A volcano plot of differential metabolites, seven marked metabolites with more than twofold change (|log2 FC|> 1) and P < 0.01 (− Log10 P > 2)

Fig. 6

A heat map demonstrating the trend of metabolites variation in M (model group) and H (IOPH group)

Fig. 7

A set of boxcharts in three metabolites which significant changed in diabetic mice and regulated by IOP

Fig. 8

Pathway analysis of metabolite sets between control and model groups

Fig. 9

The metabolic pathway network of the pathological processes of diabetes and the intervention of IOP on the molecular levels