侧柏（Platycladi cacumen，PC）源自侧柏（Platycladi orientalis (L.) Franco）的干燥枝条和叶子，具有抗癫痫作用。然而，其作用机制仍不清楚。本研究探讨了PC的潜在抗癫痫成分和机制。利用网络药理学分析PC的主要活性成分和靶标，并使用脂多糖（LPS）诱导的小鼠小胶质细胞系（BV2）通过检测活性氧（ROS）、细胞凋亡、炎症标志物、细胞迁移和信号传导途径。总共 13 种核心活性成分显示出可成药的特性，其中脱氧苦参毒素、扁柏素和异海松酸 (IPA) 预计可穿过血脑屏障。使用 SwissTargetPrediction 和相似性集成方法网站总共预测了这三种化合物的 255 个潜在目标，其中 150 个与癫痫相关。体外实验证实，IPA 通过减少迁移面积、细胞 ROS 含量、乳酸脱氢酶释放和细胞凋亡早期阶段，显着抑制 LPS 诱导的小胶质细胞氧化应激和炎症。 IPA 还可以增加抗氧化酶（超氧化物歧化酶-1 和 -2）的 mRNA 表达并抑制炎症细胞因子（白细胞介素-1β 和肿瘤坏死因子-α）。此外，IPA 磷酸化 AKT 和 mTOR 蛋白。综上所述，目前的研究结果表明，IPA 是一种源自 PC 的潜在抗癫痫化合物。版权所有：© 2024 Wang 等人。

Platycladi cacumen (PC) is derived from the dry twigs and leaves of Platycladi orientalis (L.) Franco and exerts anti-epileptic effects. However, its mechanism of action remains unknown. The present study explored the potential anti-epileptic components and mechanisms of PC. The primary active components and targets of PC were analyzed using network pharmacology and a lipopolysaccharide (LPS)-induced murine microglial cell line (BV2) was used to confirm anti-epileptic effects by detecting reactive oxygen species (ROS), apoptosis, inflammatory markers, cell migration and signaling pathways. A total of 13 core active components showed druggable properties, of which deoxypicrop odophyllotoxin, hinokinin and isopimaric acid (IPA) were predicted to cross the blood-brain barrier. In total, 255 potential targets of these three compounds were predicted using SwissTargetPrediction and Similarity Ensemble Approach websites and 150 were associated with epilepsy. In vitro experiments confirmed that IPA significantly inhibited LPS-induced microglial oxidative stress and inflammation by decreasing the migration area, cellular ROS content, lactate dehydrogenase release and early phase of apoptosis. IPA also increased the mRNA expression of anti-oxidative enzymes (superoxide dismutase-1 and -2) and suppressed inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Furthermore, IPA phosphorylated AKT and mTOR proteins. Taken together, the present findings suggested that IPA is a potential anti-epileptic compound derived from PC.Copyright: © 2024 Wang et al.