Study on the Mechanism of Panax Quinquefolium-Acorus Calamus Ameliorating Diabetic EncepHalopathy in Mice by Mediating Nrf2-Keap1 Signaling Pathway

OBJECTIVE To observe the effects of Panax quinquefolium-Acorus calamus on learning and memory abilities in diabetes mellitus(DM) mice and investigate the mechanism of Panax quinquefolium-Acorus calamus in treating diabetic cognitive impairment(DCI) through network pharmacology and animal experiments.

METHODS Diabetic mouse model was established by intraperitoneal injection of streptozotocin(80 mg·kg⁻¹), followed by 8 weeks of oral administration and assessment of drug efficacy using the Morris water maze. The active ingredients and targets of Panax quinquefolium-Acorus calamus were collected using TCMSP, Swiss Target Prediction, and Gene Cards. The protein-protein interaction network of "Traditional Chinese Medicine-Ingredient-Disease targets" was constructed using the String platform and Cytoscape, visualized, and subjected to enrichment analysis using the Metascape database. The anti-DCI mechanism of Panax quinquefolium-Acorus calamus was examined through ELISA and Western blotting, while changes in hippocampal neurons of diabetic mice were observed using HE staining.

RESULTS Panax quinquefolium-Acorus calamus reduced the escape latency of diabetic mice(P<0.05), without significant impact on swimming speed. Network pharmacology results indicated that the main components of Panax quinquefolium-Acorus calamus in treating DCI were ginsenoside Re, ginsenoside Rh2, and shanjin phenol, which regulated the Nrf2-Keap1 signaling pathway to treat DCI. Animal experiments demonstrated that Panax quinquefolium-Acorus calamus increased SOD activity(P<0.05), decreased MDA levels(P<0.01), enhanced the expression of HO-1, Keap1, Nrf2 in mouse brain(P<0.01), and alleviated the loosening of granule cell arrangement and nuclear condensation in the hippocampal CA1, CA3, and DG regions.

CONCLUSION Using animal experiments combined with network pharmacology, this study preliminarily elucidates the potential targets and mechanisms of Panax quinquefolium-Acorus calamus in intervening DCI, and predictes the molecular basis for its intervention in DCI through molecular docking, providing insights for further in-depth research on Panax quinquefolium-Acorus calamus.