Qianggan formula, a designed prescription according to the
Traditional Chinese Medicine (TCM) theory, is widely used in treating chronic
liver diseases, and indicated to prevent
blood glucose increase in patients via unknown mechanisms. To unravel the effects and underlying mechanisms of
Qianggan formula on
hyperglycemia, we administrated
Qianggan extract to high fat and high
sucrose (HFHS) diet rats. Results showed that four-week
Qianggan extract intervention significantly decreased serum fasting
blood glucose,
hemoglobin A1c, and
liver glycogen levels. Gas chromatography-mass spectrometry (GC-MS) approach was employed to explore metabolomic profiles in liver and fecal samples. By multivariate and univariate statistical analysis (variable importance of projection value > 1 and p value < 0.05), 44 metabolites (18 in liver and 30 in feces) were identified as significantly different. Hierarchical cluster analysis revealed that most differential metabolites had opposite patterns between pair-wise groups.
Qianggan extract restored the diet induced metabolite perturbations. Metabolite sets enrichment and pathway enrichment analysis revealed that the affected metabolites were mainly enriched in glycometabolism pathways such as glycolysis/gluconeogenesis, pentose phosphate pathway,
fructose, and
mannose metabolism. By compound-reaction-
enzyme-gene network analysis, batches of genes (e.g. Hk1, Gck, Rpia, etc) or
enzymes (e.g.
hexokinase and
glucokinase) related to metabolites in enriched pathways were obtained. Our findings demonstrated that
Qianggan extract alleviated
hyperglycemia, and the effects might be partially due to the regulation of glycometabolism related pathways.