Nano powder and alcohol extraction of Corni Fructus protects against diabetes in mice by ameliorating hyperglycemic and hyperlipidemia via the PI3K/AKT pathway

[Display omitted] •Use of ball milling, a method of nanotechnology, to prepare nano powder of Corni Fructus.•Nano powder of Corni Fructus could improve the symptoms of T2DM when compared with the alcohol extraction of Corni Fructus.•The molecular mechanisms of nano powder of Corni Fructus on T2DM may due to the activation of the INSR/PI3K/AKT/GLUT4 signaling pathways.•Nano powder of Corni Fructus could be a new kind of promising dosage form for the treatment of T2DM. As a traditional Chinese herbal medicine, Corni Fructus (CF) possesses varieties of pharmacological functions including anti-diabetes, anti-oxidation, anti-inflammatory, and hepatoprotective properties. However, the most commonly used forms of CF are pills and decoctions in the type 2 diabetes (T2DM) medical treatment. Until now, it remains unclear whether and how nano-powder CF (NPCF) improves T2DM. Here, we prepared NPCF via ball milling nanotechnology. NPCF significantly improved the symptoms of T2DM mice through alleviating hepatic inflammation and oxidative stress, reducing hyperglycemic and hyperlipidemic, and restoring pancreatic and liver damages. Network pharmacology screening was utilized to obtain 293 NPCF active ingredient targets and 1235 T2DM targets, and 195 cross-targets were obtained by crossover. Mechanistically, NPCF may enhance glucose transport, promote glycogen synthesis, and improve insulin resistance by acting on insulin receptor (INSR)/phosphatidylinositol 3-kinase (PI3K/AKT)/glucose transporter 4 (GLUT4) signaling pathways. Therefore, NPCF may be a potential dosage form of CF for T2DM treatment.