Wang Yan, Wang Yun, Li Chang, Liu Dong, Cai Yi, Li Qifu
Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China.
Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, International Joint Research Center of Human-Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Key Laboratory for Research and Development of Tropical Herbs and Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hainan Medical University, Haikou, Hainan 571199, P.R. China.
Exp Ther Med. 2024 Jul 3;28(3):348. doi: 10.3892/etm.2024.12637. eCollection 2024 Sep.
(PC) is derived from the dry twigs and leaves of (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. 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.
（PC）源自（L.）Franco的干燥嫩枝和叶子，具有抗癫痫作用。然而，其作用机制尚不清楚。本研究探讨了PC的潜在抗癫痫成分和机制。使用网络药理学分析了PC的主要活性成分和靶点，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、细胞迁移和信号通路来确认抗癫痫作用。共有13种核心活性成分显示出可成药特性，其中脱氧鬼臼毒素、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个潜在靶点，其中150个与癫痫相关。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，显著抑制LPS诱导的小胶质细胞氧化应激和炎症。IPA还增加了抗氧化酶（超氧化物歧化酶-1和-2）的mRNA表达，并抑制了炎症细胞因子（白细胞介素-1β和肿瘤坏死因子-α）。此外，IPA使AKT和mTOR蛋白磷酸化。综上所述，本研究结果表明IPA是一种源自PC的潜在抗癫痫化合物。
