Improved metabolic functions and gut microbiota rebalance: the therapeutic potential of <i>Ficus carica</i> polysaccharides for type 2 diabetes mellitus

The present study investigated the potential therapeutic potential of <i>Ficus carica</i> 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., <i>Lactobacillus_reuteri</i>, <i>Candidatus_Saccharimonas</i>) and suppressing opportunistic pathogens (e.g., <i>Proteobacteria</i>, <i>Gammaproteobacteria</i>, <i>Escherichia-Shigella</i>). 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 <i>via</i> the gut-hepatic axis, demonstrating its potential as a functional food for diabetes prevention and management.