Department of Emergency, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China.
Department of Geriatrics, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, PR China.
Phytomedicine. 2023 Dec;121:155119. doi: 10.1016/j.phymed.2023.155119. Epub 2023 Sep 26.
Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms.
We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment.
Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway.
Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.
先前的研究表明，葛根素具有心脏保护、血管舒张、抗炎、抗凋亡和降血糖作用。然而，葛根素对脓毒症相关性脑病（SAE）的影响仍未得到探索。在这项研究中，我们探讨了葛根素是否可以调节小胶质细胞介导的神经炎症，以治疗 SAE，并深入研究了潜在的机制。
我们通过腹腔注射脂多糖（LPS）建立了 SAE 的小鼠模型。葛根素治疗组在 LPS 暴露前给予葛根素预处理。对于体外实验，BV2 细胞在 LPS 暴露前用葛根素孵育 2 小时。我们采用网络药理学、Morris 水迷宫（MWM）测试、新物体识别（NOR）测试、免疫荧光染色、酶联免疫吸附测定（ELISA）、Western blot 和定量实时 PCR（qRT-PCR）来阐明葛根素在 SAE 治疗中的作用机制。
我们的研究结果表明，葛根素显著降低了 LPS 处理小鼠外周血中炎症细胞因子（TNF-α 和 IL-6）的产生。此外，葛根素治疗显著改善了脓毒症相关的认知障碍。葛根素还对小胶质细胞释放 TNF-α 和 IL-6 表现出抑制作用，从而防止海马神经元细胞死亡。网络药理学分析表明 AKT1 是葛根素治疗 SAE 的潜在治疗靶点。随后，我们在体内和体外实验中验证了这些结果。我们的研究最终表明，葛根素通过降低 LPS 诱导的 AKT1 磷酸化，从而降低 LPS 诱导的 AKT1 磷酸化，AKT 激活剂 SC79 通过激活 AKT1 信号通路逆转了葛根素的抗炎作用。
葛根素通过调节小胶质细胞中的 AKT1 通路对 SAE 发挥抗炎作用。
