Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway

Sagar Mahawar; Debarati Rakshit; Inklisan Patel; Swati Kailas Gore; Srijita Sen; Om Prakash Ranjan; Awanish Mishra

doi:10.1016/j.nano.2024.102752

Fisetin-loaded chitosan nanoparticles ameliorate pilocarpine-induced temporal lobe epilepsy and associated neurobehavioral alterations in mice: Role of ROS/TNF-α-NLRP3 inflammasomes pathway

Nanomedicine. 2024 May 11:59:102752. doi: 10.1016/j.nano.2024.102752. Online ahead of print.

Authors

Sagar Mahawar¹, Debarati Rakshit¹, Inklisan Patel¹, Swati Kailas Gore², Srijita Sen², Om Prakash Ranjan³, Awanish Mishra⁴

Affiliations

¹ Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, Kamrup, Assam 781101, India.
² Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, Kamrup, Assam 781101, India.
³ Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, Kamrup, Assam 781101, India. Electronic address: omprakash@niperguwahati.in.
⁴ Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Changsari, Kamrup, Assam 781101, India. Electronic address: awanish@niperguwahati.in.

PMID: 38740358
DOI: 10.1016/j.nano.2024.102752

Abstract

Fisetin has displayed potential as an anticonvulsant in preclinical studies yet lacks clinical validation. Challenges like low solubility and rapid metabolism may limit its efficacy. This study explores fisetin-loaded chitosan nanoparticles (NP) to address these issues. Using a murine model of pilocarpine-induced temporal lobe epilepsy, we evaluated the anticonvulsant and neuroprotective effects of fisetin NP. Pilocarpine-induced seizures and associated neurobehavioral deficits were assessed after administering subtherapeutic doses of free fisetin and fisetin NP. Changes in ROS, inflammatory cytokines, and NLRP3/IL-18 expression in different brain regions were estimated. The results demonstrate that the fisetin NP exerts protection against seizures and associated depression-like behavior and memory impairment. Furthermore, biochemical, and histological examinations supported behavioral findings suggesting attenuation of ROS/TNF-α-NLRP3 inflammasome pathway as a neuroprotective mechanism of fisetin NP. These findings highlight the improved pharmacodynamics of fisetin using fisetin NP against epilepsy, suggesting a promising therapeutic approach against epilepsy and associated behavioral deficits.

Keywords: Anti-inflammatory effect; Antioxidant; Chitosan nanoformulation; Fisetin; Temporal lobe epilepsy.