Department of Neurology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
Neurochem Int. 2024 Nov;180:105873. doi: 10.1016/j.neuint.2024.105873. Epub 2024 Oct 1.
Status epilepticus (SE), a continuous and self-sustaining epileptic seizure lasting more than 30 min, is a neurological emergency that can cause severe brain injuries and increase the risk for the development of epilepsy. Over the past few decades, accumulating evidence has suggested the importance of brain inflammation in the pathogenesis of epilepsy. Honokiol (HNK), a pharmacological activator of sirtuin 3 (SIRT3), is a bioactive compound extracted from the bark or leaves of Magnolia plants that possesses therapeutic benefits for preventing the development of inflammatory injury. However, the therapeutic effects of HNK against epileptic brain injury via regulating molecular mechanisms related to neuroinflammation remains elusive. Therefore, the present study investigated the effects of HNK on pilocarpine-induced status epilepticus (PCSE) and the therapeutic benefits of HNK in regulating inflammatory processes in the hippocampus. Treatment with HNK before PCSE induction attenuated the initiation of behavioral seizures. Post-treatment with HNK after SE onset increased SIRT3 expression, which mitigated glial activation, including reactive astrocytes and activated microglia, in the hippocampus following PCSE. Moreover, HNK treatment reduced the activation of the nuclear factor-κB/nucleotide-binding domain leucine-rich repeat with a pyrin-domain containing 3 inflammasome pathway, thereby inhibiting the production of interleukin-1β pro-inflammatory cytokine, subsequently alleviating PCSE-triggered apoptotic neuronal death in the hippocampus. These results indicate that HNK-induced SIRT3 upregulation has the potential to prevent the progression of epileptic neuropathology through its anti-inflammatory properties. Therefore, the present study suggests that HNK is a natural therapeutic agent for epileptic brain injury.
癫痫持续状态（SE）是一种持续且自我维持的癫痫发作，持续时间超过 30 分钟，是一种神经系统急症，可导致严重的脑损伤，并增加癫痫发生的风险。在过去的几十年中，越来越多的证据表明脑炎症在癫痫发病机制中的重要性。和厚朴酚（HNK）是一种 SIRT3 的药理学激活剂，是从木兰属植物的树皮或叶子中提取的生物活性化合物，具有预防炎症损伤发展的治疗益处。然而，HNK 通过调节与神经炎症相关的分子机制对癫痫性脑损伤的治疗作用仍不清楚。因此，本研究探讨了 HNK 对匹鲁卡品诱导的癫痫持续状态（PCSE）的影响，以及 HNK 调节海马体炎症过程的治疗益处。在 PCSE 诱导前用 HNK 治疗可减轻行为性癫痫发作的起始。SE 发作后用 HNK 治疗可增加 SIRT3 表达，减轻海马体中胶质细胞激活，包括反应性星形胶质细胞和活化的小胶质细胞。此外，HNK 治疗可降低核因子-κB/核苷酸结合结构域富含亮氨酸重复序列与含吡喃结构域的 3 炎症小体途径的激活，从而抑制白细胞介素-1β前炎症细胞因子的产生，随后减轻 PCSE 触发的海马体中神经元凋亡性死亡。这些结果表明，HNK 诱导的 SIRT3 上调具有通过其抗炎特性防止癫痫神经病理学进展的潜力。因此，本研究表明 HNK 是一种治疗癫痫性脑损伤的天然治疗剂。
