Magnolol improves postoperative cognitive dysfunction in aged mice by activating the nuclear factor erythroid 2-related factor 2/antioxidant response element pathway.

Background: The incidence of postoperative cognitive dysfunction (POCD) in elderly patients is high and related to an increased postoperative mortality rate. Magnolol has the potential to improve cognitive function, but its therapeutic effects and mechanisms of action on POCD remain unclear.

Methods: An aged mouse model of POCD was constructed using sevoflurane anesthesia and abdominal exploratory surgery. Magnolol was administered via intragastric gavage at doses of 10 or 20 mg/kg daily, starting 1 week before surgery. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown mice were used to investigate the role of the Nrf2/antioxidant response element (ARE) pathway in the therapeutic effects of magnolol on POCD.

Results: In POCD mice, magnolol treatment significantly reduced the escape latency, increased crossing numbers in the platform quadrant and target quadrant dwell time, and enhanced the novel object recognition index. Meanwhile, under the action of magnolol, the morphology of hippocampal neurons was protected, the rate of cell apoptosis was reduced, and the expression of antiapoptotic protein B-cell lymphoma 2 was upregulated. Magnolol also reduced the levels of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-1β, and reactive oxygen species, while increasing the levels of superoxide dismutase, glutathione, and glutathione peroxidase. In addition, magnolol activated proteins related to the Nrf2/ARE pathway. Notably, silencing Nrf2 weakened the effect of magnolol on improving cognitive function in POCD mice.

Conclusion: Magnolol may effectively improve POCD in aged mice by activating the Nrf2/ARE pathway.