Li Xuan, Meng Shiyu, Liu Jiayi, Sun Meixian, Zhou Mao, Ji Fengtao, Hong Yu
Department of Anesthesiology, Sun Yat-Sen Memorial Hospital, Guangzhou, China.
The Eighth People's Hospital of Qingdao, Shandong Province, China.
J Cell Mol Med. 2025 Aug;29(15):e70744. doi: 10.1111/jcmm.70744.
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.
在本研究中，我们探究了小檗碱（BBR）——一种能够穿透血脑屏障的抗炎剂——对减轻老年小鼠术后认知功能障碍（POCD）的治疗潜力。BBR以每日10毫克/千克的剂量给药，持续2周，显著改善了由手术和麻醉相关因素引起的认知障碍。具体而言，BBR显著抑制了胶质细胞的激活，并降低了促炎细胞因子如肿瘤坏死因子α（TNF-α）和白细胞介素-1β（IL-1β）的水平。此外，它减轻了氧化应激标志物和脂质积累。通过网络药理学分析，我们证明BBR通过抑制磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）途径的磷酸化来调节神经炎症、氧化过程和脂质代谢。此外，进一步的研究表明BBR上调了PPAR-γ mRNA的表达，提示其通过调节PI3K-Akt途径发挥神经保护作用。这些发现支持了BBR作为治疗老年人群POCD的治疗药物的潜在应用。
