Diabetes is a global disease that endangers human health. As reported, saponins are effective bioactive compounds for treating type 2 diabetes mellitus (T2DM) and have nontoxic side effects. This study aimed to examine the hypoglycemic effects of Polygonatum sibiricum saponin (PSS) on T2DM mice. We found that PSS could significantly decrease the levels of insulin secretion and fasting blood glucose (FBG) in T2DM mice. And the level of triacylglycerol (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the blood was decreased. In contrast, the content of high-density lipoprotein cholesterol (HDL-C) was increased. 16S rDNA sequencing was used to evaluate the changes in the gut microbiota of T2DM mice, and metabolites were analyzed by metabolomic profiling. The results showed that PSS could decrease the abundance of Firmicutes in T2DM mice, increase the abundance of Bacteroidetes. It also increased the abundance of some bacterial genera (Lactobacillus, Lachnospiraceae_NK4A136_group and Intestinimonas). The phenotypes of the gut microbiome also changed accordingly. Metabolomics analysis showed that carbohydrate metabolism and amino acid metabolisms, such as L-alanine and L-glutamic acid, were greatly affected by PSS. In addition, the levels of inositol and chlorogenic acid in metabolites also increased significantly under PSS intervention. In general, PSS could exert its hypoglycemic effect, regulate the gut microbiota and affect the metabolism of T2DM mice.

Polygonatum sibiricum is a medicinal and homologous plant grown in China, which is commercially available without the provision of medical prescription. Saponin is one of the biologically active components of Polygonatum sibiricum. This study aimed to extract saponin from Polygonatum sibiricum (PSS) and to investigate its hypoglycemic effect and effect on gut micorbiota in diabetic mice. Through single factor and orthogonal experiments, the extraction conditions of saponin were optimized, and the content of saponin in the extract was 3.07 ± 0.02 mg g⁻¹. During the experiment evaluating the hypoglycemic ability, it was found that PSS could inhibit the activity of α-amylase and α-glucosidase at first. Then, HepG2 was used to observe the effect of the saponin on insulin resistance. The results showed that PSS could significantly improve the state of insulin resistance in IR-HepG2 cells, increase the glucose consumption and intracellular glycogen content of cells, and the activity of hexokinase (0.455 ± 0.007 μmol min⁻¹ g⁻¹) and pyruvate kinase (0.174 ± 0.038 U per g prot). Finally, it was found that PSS could alleviate the symptoms of polyphagia and polydipsia in diabetic mice, regulate the gut microbiota of diabetic mice, increase the number of probiotics, and reduce the number of harmful bacteria. In summary, PSS may play an important role in regulating diabetes and can be developed as a promising natural material for diabetes prevention and treatment.

Type 2 diabetes mellitus (T2DM) is a systemic metabolic disorder characterized by insulin deficiency and insulin resistance. Recently, it has become a significant threat to public health. Polygonatum sibiricum saponin (PSS) has potential hypoglycemic effects, but its specific mechanism needs further study. In this study, PSS significantly decreased the level of blood glucose, water intake, and the organ index in diabetic mice. Meanwhile, PSS effectively reduced the content of total triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the blood, and increased the content of high-density lipoprotein cholesterol (HDL-C). This suggests that PSS could reduce the content of blood lipids and initially improve the damage of hepatocytes. We found that PSS alleviated hepatic insulin resistance, repaired islet beta cells, and enabled insulin to play its biological role normally. It also improved oral glucose tolerance and abated serum lipopolysaccharide (LPS) and glycosylated hemoglobin (HbA1c) levels in T2DM mice. Furthermore, studies have found that PSS increased the content of phosphorylated protein kinase B (AKT), thereby promoting the effect of glucose transporter 4 (GLUT-4), and activating glycogen synthase kinase 3beta (GSK-3β) and glycogen synthase (GS) proteins to promote hepatic glycogen synthesis. Finally, we found that PSS could promote the growth of beneficial bacteria such as Bifidobacterium and Lactobacillus, reduce the growth of harmful bacteria such as Enterococcus and Enterobacter, and preliminarily improve the composition of important bacteria in the intestine. These studies indicate that PSS has an excellent hypoglycemic effect, which provides a potential new treatment for T2DM and guidance for more in-depth research.