Abstract
Glehniae Radix, the dried root of Glehnia littoralis Fr. Schmidt ex Miq. (Apiaceae), exhibits diverse biological activities. However, research on the hypoglycemic effects of Glehniae Radix polysaccharides (GRPs), particularly in vivo studies clarifying their mechanisms of action, remains limited. This study aimed to verify the in vivo hypoglycemic activity of crude GRP in a diabetic model and to elucidate its mechanism. GRP was extracted by water extraction and ethanol precipitation, yielding an extraction rate of 38% and a polysaccharide content of 73.48%. Its hypoglycemic effects and mechanisms were investigated in female B6.BKS(D)-Leprdb/J (db/db) mice following daily administration of GRP at doses of 300 and 600 mg/kg for five consecutive weeks. Following GRP administration, mice in the CH group (600 mg/kg) exhibited a mean reduction in fasting blood glucose levels of approximately 40.7% and an improvement in insulin tolerance test (ITT) outcomes by about 28.4%. Additionally, GRP alleviated damage to the liver, kidney, and colon; decreased hepatic total cholesterol (TC) and triglycerides (TGs) by approximately 40.8% and 24.6%, respectively; and increased colonic Zonula Occludens-1 (ZO-1) expression by an average of 49.5%. Mechanistically, GRP significantly upregulated the expression of peroxisome proliferator-activated receptor-α (PPAR-α) and PPAR-γ in the liver, while also increasing the abundance of beneficial gut bacteria such as Alistipes and suppressing harmful bacteria including Escherichia-Shigella. Furthermore, GRP activated the galactose metabolism pathway and inhibited abnormal enrichment of the steroid biosynthesis pathway, collectively ameliorating glucose metabolic disorders in female db/db mice via the "gut microbiota-PPAR signaling axis". In light of these results, GRP exerts significant in vivo hypoglycemic effects by modulating gut microbiota balance and activating the PPAR signaling pathway.