Echinacoside, an Active Constituent of Cistanche Herba, Exerts a Neuroprotective Effect in a Kainic Acid Rat Model by Inhibiting Inflammatory Processes and Activating the Akt/GSK3β Pathway

• Published in: Biological & pharmaceutical bulletin 2018/11/01, Vol.41(11), pp.1685-1693
• Main Authors: Lu, Cheng Wei, Hsieh, Hsi Lung, Lin, Tzu Yu, Hsieh, Ting Yang, Huang, Shu Kuei, Wang, Su Jane
• Format: Article
• Language: English
• Subjects: Acids; AKT protein; Alternations; Animals; Bcl-2 protein; Brain - cytology; Brain - drug effects; Brain - metabolism; Cistanche - chemistry; Cytokines - metabolism; Disease Models, Animal; echinacoside; Epilepsy; Epilepsy - etiology; Epilepsy - metabolism; Epilepsy - pathology; Epilepsy - prevention & control; Excitotoxicity; Gene expression; Glutamic Acid - adverse effects; Glutamic Acid - metabolism; Glycogen; Glycogen synthase kinase 3; Glycogen Synthase Kinase 3 beta - metabolism; Glycosides - pharmacology; Glycosides - therapeutic use; Hippocampus; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - prevention & control; Inflammatory response; Kainic Acid; Kinases; Male; Microglia - drug effects; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; neuroprotective effect; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - metabolism; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - prevention & control; Phosphorylation; Phytotherapy; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats, Sprague-Dawley; Rodents; Seizures; Seizures - chemically induced; Seizures - metabolism; Seizures - prevention & control; Signal Transduction
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00407

Echinacoside is a major compound of Cistanche Herb and has glutamate release-inhibiting activity in the brain. Given the involvement of excitotoxicity caused by massive glutamate in the pathophysiology of epilepsy, we explored the antiepileptic effect of echinacoside on kainic acid-induced seizures in rats. The rats were intraperitoneally administrated echinacoside for 30 min prior to intraperitoneal injection with kainic acid. The results showed that kainic acid induced seizure-like behavioral patterns, increased glutamate concentrations, caused neuronal loss and microglial activation, and stimulated proinflammatory cytokine gene expression in the hippocampus. These kainic acid-induced alternations were found to be attenuated by echinacoside pretreatment. Furthermore, decreased Akt and glycogen synthase kinase 3β (GSK3β) phosphorylation as well as Bcl-2 expression in the hippocampus was reversed by the echinacoside pretreatment. These results demonstrate that echinacoside exert its antiepileptic and neuroprotective actions in a kainic acid rat model through suppressing inflammatory response and activating the Akt/GSK3β signaling. Therefore, the present study suggests that echinacoside is the potentially useful in the prevention of epilepsy.