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Therapeutic effects of scoparone on pilocarpine (Pilo)-induced seizures in mice. | LitMetric

Therapeutic effects of scoparone on pilocarpine (Pilo)-induced seizures in mice.

Biomed Pharmacother

Institute of Neurology, China Three Gorges University, Yichang, Hubei 443002, PR China.

Published: January 2018

AI Article Synopsis

  • Epilepsy is a serious neurological condition associated with inflammation and cell death in the brain, prompting researchers to explore potential treatments.
  • The study focused on scoparone, a compound known for its anti-inflammatory properties, to see if it could prevent seizures from causing damage to the blood-brain barrier and reduce inflammation and cell death in rat models of epilepsy.
  • Results showed that scoparone effectively lowered inflammation and apoptosis markers in the brain by inhibiting specific pathways (TLR4/NF-κB and PI3K/AKT), suggesting it could be a promising therapeutic option for managing epilepsy-related damage.

Article Abstract

Epilepsy is a common and devastating neurological disorder. Inflammatory processes and apoptosis in brain tissue have been reported in human epilepsy. Scoparone (6,7-dimethoxycoumarin) is an important chemical substance, which has multiple beneficial activities, including antitumor, anti-inflammatory and anti-coagulant properties. In our present study, we attempted to investigate if scoparone could attenuate seizures-induced blood brain barrier breakdown, inflammation and apoptosis. Pilocarpine (Pilo) and methylscopolamine were used to establish acute seizure animal model. Scoparone suppressed the leakage of blood brain barrier, inflammation and apoptosis. In hippocampus and cortex, the expression of inflammation-associated molecules, such as chemokine (CXC motif) ligand 1 (CXCL-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, hypoxia-inducible factor 1α (HIF-1α), and monocyte chemoattractant protein-1 (MCP-1), were reduced by scoparone through inactivating toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) pathway. Scoparone reduced apoptotic levels in hippocampus by TUNEL analysis, along with decreased Caspase-3 and PARP cleavage. In addition, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway in Pilo-induced acute seizures was also inactivated by scoparone. In vitro, we confirmed that scoparone inhibited LPS-caused astrocytes activation as proved by the reduced glial fibrillary acidic protein (GFAP) levels, inflammation and apoptosis, which were at least partly dependent on AKT suppression. The results above indicated that scoparone could relieve pilocarpine (Pilo)-induced seizures against neural cell inflammation and apoptosis.

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Source
http://dx.doi.org/10.1016/j.biopha.2017.09.127DOI Listing

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