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

Abstract

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.