The present study investigated the potential therapeutic potential of Ficus carica polysaccharides (FCPS) in type 2 diabetic mellitus (T2DM) mice, focusing on elucidating the underlying molecular mechanisms. Network pharmacology analysis identified 37 shared targets between FCPS and T2DM, including perixisome proliferator activated receptor alpha (PPARα), highlighting the significance of PPAR signaling pathways in FCPS-mediated T2DM treatment. The results demonstrated that FCPS treatment significantly reduced markers of glucose and lipid metabolism (fasting blood glucose (FBG), nonestesterified fatty acid (NEFA), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C)), inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1)), and liver damage (glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT)) in T2DM mice. Additionally, FCPS ameliorated hepatic lipid droplet accumulation, fatty degeneration, and hepatocyte structural abnormalities. Western blot analysis confirmed FCPS-induced upregulation of key proteins in the IRS-1/AKT/PPARα signaling pathway, (insulin receptor substrate 1 (IRS-1), phosphatidyqinositol-3 kinase (PI3K), phospho-protein kinase B (p-AKT), glucose transporter 2 (GLUT2), phospho-glycogen synthase kinase 3 beta (p-GSK-3β), phospho-adenosine 5′-monophosphate-activated protein kinase alpha (p-AMPKα), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), PPARα, peroxisome proliferator-activated receptor gamma (PPARγ)) and downregulation of GSK-3β, sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). 16S rRNA sequencing results revealed FCPS's ability to modulate gut microbiota dysbiosis in T2DM mice by promoting beneficial bacteria (e.g., Lactobacillus_reuteri, Candidatus_Saccharimonas) and suppressing opportunistic pathogens (e.g., Proteobacteria, Gammaproteobacteria, Escherichia-Shigella). These findings collectively suggest that FCPS has a marked effectiveness in improving glucose and lipid metabolism, decreasing inflammatory responses, as well as modulating the gut microbiota in T2DM mice via the gut-hepatic axis, demonstrating its potential as a functional food for diabetes prevention and management.

To explore the establishment of insulin resistance model of HepG2(IR-HepG2) induced by high glucose, dexamethasone and insulin, to detect the effect of Pleurotus eryngii polysaccharides, Ziziphus jujuba polysaccharides and Lycium barbarum polysaccharides on improving insulin resistance of liver cells in vitro, and to analyze the effect of three polysaccharides on hypoglycemic. Different concentrations of dexamethasone, insulin and their combination were selected to induce the insulin resistance of HepG2 cells in high glucose culture. MTT method was used to detect the effect of different inducers on the activity of HepG2 cells. Glucose oxidase method was used to detect the glucose content in the supernatant of cell culture. At the same time, the stability of IR-HepG2 cell model was detected after removing inducers. IR-HepG2 cells were treated with three kinds of natural polysaccharides at different concentrations. The effects of polysaccharides on cell viability and insulin resistance were detected by MTT and glucose oxidase methods respectively. Dexamethasone(3.75 μmol/L) combined with insulin(0.001 μmol/L) can successfully induce IR-HepG2 cell model in high glucose culture condition, and has no significant effect on cell activity, and the model can keep stable within 72 hours. Lycium barbarum polysaccharides had better hypoglycemic effects in vitro.