Malekshahi Mahda, Meskar Zohreh, Manavi Mohammad Amin, Lesani Ali, Mohammad Jafari Razieh, Ghasemi Mehdi, Dehpour Ahmad Reza
Experimental Medicine Research Center, Tehran University of Medical Sciences (TUMS), P. O. Box 13145-784, Tehran, Iran.
Department of Pharmacology, School of Medicine, TUMS, Tehran, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 26. doi: 10.1007/s00210-025-04096-w.
This study investigates the efficacy of noscapine in mitigating lithium-pilocarpine-induced Status epilepticus (SE) in rats and explores its impact on Nrf2/HO-1/NLRP3 signaling pathways, along with IL-1β and IL-18 modulation. SE was induced in male rats using lithium (127 mg/kg, intraperitoneal (i.p.)) and pilocarpine (60 mg/kg, i.p.). Noscapine (0.1, 1, 3, 10, 30, 100 mg/kg, i.p.) or its vehicle was administered 30 min before the SE induction. Seizure activity was monitored, and the effective dose of noscapine was identified. Western blotting was performed to analyze the expression levels of Nrf2, HO-1, and NLRP3, while ELISA was used to measure IL-1β and IL-18 levels, all in the hippocampus, which is critically involved in epilepsy pathophysiology. Noscapine at 30 mg/kg significantly (p < 0.01) reduced seizure severity and duration. Molecular analysis revealed that noscapine modulated the Nrf2/HO-1/NLRP3 pathway and reduced levels of pro-inflammatory cytokines IL-1β and IL-18 (p < 0.01). Noscapine exhibits potent anticonvulsive effects in a lithium-pilocarpine model of SE in rats, likely mediated through modulation of the Nrf2/HO-1 pathway and the NLRP3 inflammasome pathways. Further studies are warranted to explore its therapeutic potential in epilepsy.
本研究调查了诺司卡品在减轻大鼠锂-匹罗卡品诱导的癫痫持续状态（SE）方面的疗效，并探讨了其对Nrf2/HO-1/NLRP3信号通路以及白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）调节的影响。使用锂（127mg/kg，腹腔注射（i.p.））和匹罗卡品（60mg/kg，i.p.）在雄性大鼠中诱导SE。在SE诱导前30分钟给予诺司卡品（0.1、1、3、10、30、100mg/kg，i.p.）或其溶媒。监测癫痫发作活动，并确定诺司卡品的有效剂量。进行蛋白质免疫印迹法以分析Nrf2、HO-1和NLRP3的表达水平，同时使用酶联免疫吸附测定法测量海马体中IL-1β和IL-18的水平，海马体在癫痫病理生理学中起关键作用。30mg/kg的诺司卡品显著（p<0.01）降低了癫痫发作的严重程度和持续时间。分子分析表明，诺司卡品调节了Nrf2/HO-1/NLRP3通路，并降低了促炎细胞因子IL-1β和IL-18的水平（p<0.01）。诺司卡品在大鼠锂-匹罗卡品诱导的SE模型中表现出强大的抗惊厥作用，可能是通过调节Nrf2/HO-1通路和NLRP3炎性小体通路介导的。有必要进一步研究其在癫痫治疗中的潜力。
