Berberine Alleviates Neuroinflammation in Isoflurane-Stimulated Primary Rat Hippocampal Neuron Cells via Modulating PI3K/AKT/NF-κB Pathway

Background: Berberine (Ber) is effective in alleviating postoperative cognitive dysfunction in mice. However, the function of Ber on isoflurane-stimulated primary rat hippocampal neurons (RHN) is still unknown. Objective: To investigate the role of Ber in isoflurane-stimulated primary RHN. Methods: To reveal the toxicity of Ber (0, 2.5, 5, 10, 15, and 20 mu M) on RHN cells, cell counting kit-8 (CCK-8) assay was conducted. Immunofluorescence was utilized to identify primary RHN cells. The role of Ber in apoptosis and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor kappa B (NF-kappa B) pathway-related markers in Iso (isoflurane)-stimulated RHN cells was assessed through enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription PCR (RT-qPCR), and Western blot. After the treatment using PI3K inhibitor wortmannin (Wor), apoptosis and PI3K/AKT/NF-kappa B pathway-related markers were tested again. Results: Ber (10, 15, and 20 mu M) suppressed the viability of RHN cells. Neuron-specific nuclear protein (NeuN) was positive in primary RHN cells. Ber also blocked apoptosis, decreased tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1 beta, and NF-kappa B family member REL-1A (P65) levels, and elevated PI3K and p-AKT levels in Iso-treated RHN cells, but these effects were counteracted by Wor. Conclusions: Ber mitigates neuroinflammation in Iso-mediated RHN cells via modulating the PI3K/AKT/NF-kappa B pathway. Ber might serve as a latent agent for postoperative cognitive dysfunction (POCD) therapy.