Berberine Ameliorates Postoperative Cognitive Dysfunction in Aged Mice and Regulates the PI3K‐AKT Pathway: A Network Pharmacology Study

In this study, we investigated the therapeutic potential of Berberine (BBR), an anti‐inflammatory agent capable of penetrating the blood–brain barrier, for mitigating postoperative cognitive dysfunction (POCD) in aged mice. BBR was administered at a dose of 10 mg/kg daily for 2 weeks and significantly improved cognitive impairments induced by surgical and anaesthesia‐related factors. Specifically, BBR markedly suppressed glial cell activation and reduced levels of pro‐inflammatory cytokines such as tumour necrosis factor alpha (TNF‐α) and interleukin‐1 beta (IL‐1β). Additionally, it alleviated oxidative stress markers and lipid accumulation. Using network pharmacology analysis, we demonstrated that BBR modulates neuroinflammation, oxidative processes and lipid metabolism by inhibiting the phosphorylation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) pathway. Furthermore, extended research revealed that BBR upregulated the expression of PPAR‐ γ mRNA, suggesting a neuroprotective mechanism via regulation of the PI3K‐Akt pathway. These findings support the potential application of BBR as a therapeutic agent for managing POCD in elderly populations.