Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats

Chang, Chia Ying; Lin, Tzu-Yu; Lu, Cheng Wei; Huang, Shu Kuei; Wang, Ying Chou; Chou, Shang Shing P.; Wang, Su‐Jane

doi:10.1016/j.neuro.2015.08.014

Cited by 43 publications

(15 citation statements)

References 65 publications

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“…Synaptosomes were purified from the cerebral cortex of rats on discontinuous Percoll gradients as described previously [ 43 , 44 ]. Briefly, the tissue was homogenized in medium containing 0.32 M sucrose (pH 7.4), the homogenate was centrifuged for 10 min at 3000× g (5000 rpm in a JA 25.5 rotor; Beckman Coulter, Inc., Miami, FL, USA) and 4 °C, and the supernatant was centrifuged again for 12 min at 14,500× g (11,000 rpm in a JA 25.5 rotor).…”

Section: Methodsmentioning

confidence: 99%

Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca2+ Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals

Lin

Huang

et al. 2016

IJMS

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The glutamatergic system may be involved in the effects of neuroprotectant therapies. Echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Herba Cistanche, has neuroprotective effects. This study investigated the effects of echinacoside on 4-aminopyridine-evoked glutamate release in rat cerebrocortical nerve terminals (synaptosomes). Echinacoside inhibited Ca2+-dependent, but not Ca2+-independent, 4-aminopyridine-evoked glutamate release in a concentration-dependent manner. Echinacoside also reduced the 4-aminopyridine-evoked increase in cytoplasmic free Ca2+ concentration but did not alter the synaptosomal membrane potential. The inhibitory effect of echinacoside on 4-aminopyridine-evoked glutamate release was prevented by ω-conotoxin MVIIC, a wide-spectrum blocker of Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but was insensitive to the intracellular Ca2+ release-inhibitors dantrolene and 7-chloro-5-(2-chloropheny)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157). Furthermore, echinacoside decreased the 4-aminopyridine-induced phosphorylation of protein kinase C, and protein kinase C inhibitors abolished the effect of echinacoside on glutamate release. According to these results, we suggest that the inhibitory effect of echinacoside on evoked glutamate release is associated with reduced voltage-dependent Ca2+ entry and subsequent suppression of protein kinase C activity.

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Section: Methodsmentioning

confidence: 99%

Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca2+ Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals

Lin

Huang

et al. 2016

IJMS

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“…Inhibition of NMDA receptors at the glycine binding site and agonistic activity on GABA A receptors can be considered as the possible mechanism of action for the anticonvulsant effect of orange juice [21]. In another study performed by Chang et al [22], citrus flavonoid hesperidin was found to reduce kainic acid-induced neuronal damage and glutamate excitotoxicity in the rat hippocampus. In the same study, it was proposed that hesperidin attenuates 4-Aminopyridine (4-AP) mediated elevation in cytosolic Ca 2+ and presynaptically inhibits glutamate release in vitro in the synaptosomes (hippocampal nerve terminals) [22].…”

Section: Flavonoids and Epilepsymentioning

confidence: 99%

Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy

Sharma

Kumar

Singh

2019

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cAMP response element binding protein (CREB) is a key transcriptional regulator that regulates the transcription of genes related with neuronal differentiation, synaptic plasticity, learning and memory. Brain derived neurotrophic factor (BDNF), is a CREB dependent gene which plays a pivotal role in the pathogenesis of epilepsy and central comorbid conditions associated with epilepsy. However, the beneficial or detrimental consequences of CREB-BDNF activation on the induction and/or progression of seizures depend specifically on the region of brain involved and the time of activation. The bioactive molecules that alter the activity of CREB in a way to have specialized effects in different brain regions and neural circuits involved could potentially be utilized for therapeutic purposes. Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF. Several members of flavonoid family have also showed suppression of epileptic seizures via interaction with CREB/BDNF pathway. Moreover, epilepsy is often accompanied by a number of behavioural and psychological comorbid conditions that further gets aggravated by the use of conventional antiepileptic drug therapy. Multiple studies have also supported the beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway. The current review is an attempt to collate the available preclinical and clinical studies to establish the therapeutic potential of various dietary flavonoids in comprehensive management of epilepsy with relation to CREB-BDNF pathway.

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“…Neuroinflammation contributes considerably to delayed brain damage after acute injury and exerts a detrimental effect on a neurological outcome. 27) Inflammatory responses, such as microglia activation and inflammatory cytokine production, has been described in human epilepsy and in experimental models of epilepsy. 36,48) Moreover, the release of these proinflammatory cytokines from the activated microglial cells promotes kainic acid-induced neuronal damage in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…25) The dose and schedule of administration were chosen on the basis of previous studies. 22,26,27) The experiments on animals were approved by the Institutional Animal Care and Use Committee at the Fu Jen Catholic University, and carried out in accordance with the protocols issued, which followed National Institutes of Health Guide for the Care and Use of Laboratory (NAC 2011).…”

Section: Methodsmentioning

confidence: 99%

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

Hsieh

Lin

et al. 2018

Biological & Pharmaceutical Bulletin

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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.

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Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats

Cited by 43 publications

References 65 publications

Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca2+ Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals

Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca2+ Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals

Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy

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

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