Aim
This investigation was intended to determine the potential neuroprotective impact of morin hydrate (MH), zeolite clinoptilolite (ZC), and/or physical and mental activities (PhM) on an aluminum chloride (AlCl3)-induced AD rat model.
Conclusion
This research highlights the neuroprotective impact of MH and ZC plus PhM against AlCl3-induced AD via modulation of Nrf2/HO-1/GPX4, TLR4/NF-κβ/NLRP3, APOE4/LRP1, and Wnt3/β-catenin/GSK-3β signaling pathways. It is the first to point out the inclusion of ferroptosis-Nrf2/inflammasomes cross-talk in the neuroprotection mechanism of MH/ZC against the AlCl3-mediated AD model.
Methods
Male Sprague Dawley rats were randomly allocated into seven groups. Group I was the control group. Groups II-VII were treated with AlCl3 for 5 weeks. Groups III-VII were tested for the effects of MH, ZC, and/or PhM. Biochemical, brain histopathological, and behavioral studies were performed.
Results
PhM, MH, and ZC combined therapy exhibited a significant neuroprotective effect demonstrated by corrected catecholamines and tau and β-amyloid levels, as well as the antioxidant and anti-ferroptotic effects probably through Nrf2/HO-1/GPX4 and ACSL4 signaling pathways. In addition, combined therapy counteracted the inflammatory responses through modulating the TLR4/NF-κβ/NLRP3 inflammasome expression. Moreover, combined therapy groups showed the maximum improvement of both APOE4/LRP1 and Wnt3/β-catenin/GSK-3β signaling expressions.