Lachnum singerianum Polyphenols Alleviate Hyperglycemia in Streptozotocin-Induced Diabetic Mice via the IRS/Akt/GSK-3β Pathway

This study evaluated the antihyperglycemic effects and mechanisms of Lachnum singerianum polyphenols (LPs) in streptozotocin-induced diabetic mice. LP was obtained via ethanol extraction, purified using XAD-4 resin, and characterized by LC-MS/MS. Diabetic mice were administered low- or high-dose LP (50 or 100 mg/kg), metformin, or their combination for 6 weeks. Metabolic parameters, organ indices, serum and liver biomarkers, histopathology, and signaling pathways were assessed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified LP as flavonoid-, tannin-, and phenolic acid-enriched fractions. LP treatment significantly ameliorated hyperglycemia, as evidenced by reduced fasting blood glucose, improved glucose and insulin tolerance, and restored homeostasis model assessment indices. Furthermore, LP alleviated hepatic injury, attenuated oxidative stress, and ameliorated dyslipidemia, with histopathological analysis confirming protective effects on pancreatic islets and liver tissues. Mechanistically, LP activated the insulin receptor substrate (IRS)/protein kinase B (Akt)/glycogen synthase kinase (GSK)-3β pathway by enhancing IRS-2/Akt phosphorylation and suppressing GSK-3β expression. This is the first study to characterize the bioactive polyphenols from L. singerianum and demonstrate their multitarget efficacy against diabetic hyperglycemia through coordinated modulation of insulin resistance, oxidative stress, and lipid metabolism.