Effect of salvianolic acid A on glucose and lipid metabolism in diabetic rats based on intestinal flora and metabolomics
XU Jin-yao,ZOU Zhen-kai,LI Xuan-yi
Abstract:
Objective To explore the possible mechanism of salvianolic acid A in treating type 2 diabetes based on intestinal flora and metabolomics. Methods Eight out of thirty SD rats were randomly selected to serve as the normal control group, while the remaining rats were subjected to a high-fat diet in conjunction with intraperitoneal injections of streptozotocin (STZ, 35 mg/kg) to establish a type 2 diabetes mellitus (T2DM) rat model. The sixteen rats that successfully developed the model were then randomly divided into two groups: the model group and the salvianolic acid A group. The salvianolic acid A group received intragastric administration of salvianolic acid A (1mg/kg) for a duration of eight weeks. Subsequently, OGTT and ITT were performed on the rats, and serum levels of TC, TG, LDL-C and HDL-C were measured. Additionally, 16S rRNA high-throughput sequencing and liquid chromatography-tandem mass spectrometry methods were employed to assess changes in bacterial flora and intestinal metabolites in the rat intestines. Results Compared to the control group, the blood glucose levels and area under the curve (AUC) of the model group were significantly elevated at each time point (P <0.01). Additionally, serum levels of TC, TG and LDL-C were also significantly increased (P <0.01). Conversely, the serum Chao1 index, ACE index, and Shannon index were found to be decreased. The relative abundances of Clostridia, Lachnospirales, Clostridia_UCG-014, Lachnospiraceae, Muribaculaceae, and Oscillospiraceae were reduced, while the relative abundance of Bacilli, Oscillospirales, and Lactobacilaceae increased (P <0.05). A total of 18 distinct metabolites were identified between the control and model groups, with significant differences noted for salvianolic acid A. Among the groups, there were 12 types of metabolites identified, with 3 types classified as common differential metabolites across all three groups. In comparison to the control group, glycodeoxycholic acid and glycoursodeoxycholic acid were down-regulated in the model group. Conclusion Salvianolic acid A has an improving effect on T2DM rats, and its mechanism may be related to regulating intestinal flora and changing serum metabolites.