Eleutheroside B liposomes ameliorate type 2 diabetes mellitus by modulating glucose and lipid metabolism: A metabolomic study.

BACKGROUND

Eleutheroside B (EB), a bioactive compound from Acanthopanax senticosus, has notable hypoglycemic effects. However, its low solubility and limited bioavailability constrain clinical application.

PURPOSE: This study aimed to develop novel Eleutheroside B liposomes (EB-LIP) to overcome these limitations and evaluate their therapeutic efficacy in a type 2 diabetes mellitus (T2DM) mouse model. We also examined the molecular mechanisms underlying the improved metabolic effects of EB-LIP, focusing on key signaling pathways in glucose and lipid metabolism.

METHODS

EB-LIP was synthesized using the ethanol injection method, a process optimized to enhance EB solubility and stability. Therapeutic efficacy was assessed in a T2DM model induced by a high-fat, high-sugar diet in combination streptozotocin. Mice received varying doses of free EB or 100 mg/kg EB-LIP via gavage. We measured blood glucose, lipid profiles, and insulin sensitivity. Histopathological examination assessed tissue damage in major organs. Liver metabolomics identified differential metabolites and predicted altered regulatory pathways. Complementary in vitro studies using high glucose-induced C2C12 cells validated molecular effects, focusing on AMPK signaling pathway and GLUT4 expression.

RESULTS

EB-LIP achieved high encapsulation efficiency (85.90%) and may improve EB solubility and stability. Administration of EB-LIP at 100 mg/kg elicited a stronger hypoglycemic effect compared with the free EB administered at an equivalent dose, and also significantly improved lipid metabolism, and alleviated tissue damage associated with T2DM. Metabolomic analysis identified 303 differential metabolites and revealed that EB-LIP modulated key metabolic pathways, including the AMPK signaling pathway, PPAR signaling pathway, insulin resistance, and glycerophospholipid metabolism. In vitro experiments confirmed that EB-LIP enhances AMPK phosphorylation and GLUT4 expression, improving insulin resistance.

CONCLUSION

EB‑LIP may improve the bioavailability of EB and exert its antidiabetic effects via multi‑target and multi‑pathway mechanisms. This study supports developing phytochemical-based nanomedicines for complex metabolic diseases.