Novel Hesperetin Solid Lipid Nanoparticles Attenuates Inflammatory Gene Expression and Astrocyte Activation in Pentylenetetrazol-Induced Kindling Model of Epilepsy

Introduction: Epilepsy is one of the most common chronic neurological disorders, which provoke progressive neuronal degeneration and memory impairment. In recent years, application of herbal compounds with anti-inflammatory properties, such as hesperetin has been introduced as useful agent in reducing of the epilepsy symptoms. Despite the numerous pharmacological activities of hesperetin, its biomedical application has been hampered, because of poor water solubility and low oral bioavailability. we fabricated a novel form of hesperetin solid lipid nanoparticles (SLNPs). The effect of these prepared NPs was evaluated on inflammatory gene expression, neuronal density and astrocyte activation in pentylenetetrazol (PTZ)-induced kindling model. Method and material: hesperetin-loaded NPs were prepared using a propylene glycol with stearic acid and pluronic F68 polymer. Male NMRI mice have received the daily injection of hesperetin and hesperetin- loaded NPs at dose of 10 and 20 mg/kg. All interventions were injected intraperitoneally (i.p.), 10 days before PTZ administration and the injections were continued until 1 h before each PTZ injection. Animals have received their last injections of PTZ and then, brain tissues were removed. Immunostaining against NeuN and GFAP respectively as mature neuronal and astrocyte markers were performed on brain sections. QRT-PCR was done for inflammatory gene expression in hippocampus. Result: Our data showed successful fabrication of hesperetin-loaded NPs. In comparison to free hesperetin, hesperetin NPs markedly reduced seizure behavior, neuronal loss, and astrocyte activation in a PTZ-induced kindling model. Results showed that hesperetin administration attenuates inflammatory gene expression in fully kindled animals. Conclusion: Overall, the results of this study suggest that hesperetin NPs administration effectively ameliorates inflammatory gene expression and alleviates the level of neuronal death and astrocyte activation in PTZ-induced kindling model.

کلیدواژه ها:

Epilepsy ، hesperetin NPs ، inflammatory gene expression ، Neuronal loss ، astrocyte activation