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Anticonvulsant Effects of Noscapine Against Status Epilepticus Induced by Lithium-Pilocarpine in Rats: Involvement of Nrf2/Ho-1 and Nlrp3 Pathways Publisher



Malekshahi M1, 2 ; Meskar Z1, 2 ; Manavi MA1, 3 ; Lesani A1, 2 ; Mohammad Jafari R1, 2 ; Ghasemi M4 ; Dehpour AR1, 2
Authors
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Authors Affiliations
  1. 1. Experimental Medicine Research Center, Tehran University of Medical Sciences (TUMS), P. O. Box 13145-784, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, TUMS, Tehran, Iran
  3. 3. Department of Toxicology and Pharmacology, Faculty of Pharmacy, TUMS, Tehran, Iran
  4. 4. Department of Neurology, Lahey Hospital and Medical Center, 41 Mall Road, Burlington, 01803, MA, United States

Source: Naunyn-Schmiedeberg's Archives of Pharmacology Published:2025


Abstract

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. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.
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