Abstract
Asperuloside (ASP) and geniposide (GP) are iridoids that have shown various biological properties, such as reduction of inflammation, oxidative stress, and neuroprotection. The aim of this study was to investigate the mechanism of action of ASP and GP through the experimental model of pilocarpine-induced seizures. Mice were treated daily with saline, valproic acid (VPA), GP (5, 25, or 50 mg/kg), or ASP (20 or 40 mg/kg) for 8 days. Pilocarpine (PILO) treatment was administered after the last day of treatment, and the epileptic behavior was recorded for 1 h and analyzed by an adapted scale. Afterward, the hippocampus and blood samples were collected for western blot analyses, ELISA and comet assay, and bone marrow to the micronucleus test. We evaluated the expression of the inflammatory marker cyclooxygenase-2 (COX-2), GluN2B, a subunit of the NMDA receptor, pGluR1, an AMPA receptor, and the enzyme GAD-1 by western blot and the cytokine TNF-α by ELISA. The treatments with GP and ASP were capable to decrease the latency to the first seizure, although they did not change the latency to status epilepticus (SE). ASP demonstrated a genotoxic potential analyzed by comet assay; however, the micronuclei frequency was not increased in the bone marrow. The GP and ASP treatments were capable to reduce COX-2 and GluN2B receptor expression after PILO exposure. This study suggests that GP and ASP have a protective effect on PILO-induced seizures, decreasing GluN2B receptor and COX-2 expression.
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The datasets generated during the current study are available in the supplementary material.
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This work was supported by the Higher Education Personnel Improvement Coordination (CAPES) and the Federal University of Rio Grande do Sul (UFRGS).
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All authors contributed to the study’s conception and design. Mariana Uczay and Pricila Pflüger carried out the assays in the study and participated in the drafting of the manuscript. Gilsane von Poser and Maria Helena Vendruscolo extracted the compounds and participated in the drafting of the manuscript. Iraci Torres provided reagents and participated in the drafting of the manuscript. Helouise Richardt Medeiros helped with the measurement of TNF-α and João Denis Medeiros de Oliveira the comet assay. Jaqueline Nascimento Picada and Patrícia Pereira conceived, designed, supervised the study, and drafted the manuscript. All authors read and approved the final manuscript.
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Uczay, M., Pflüger, P., Picada, J.N. et al. Geniposide and asperuloside alter the COX-2 and GluN2B receptor expression after pilocarpine-induced seizures in mice. Naunyn-Schmiedeberg's Arch Pharmacol 396, 951–962 (2023). https://doi.org/10.1007/s00210-022-02367-4
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DOI: https://doi.org/10.1007/s00210-022-02367-4