1.Beneficial Effects of Silibinin Against Kainic Acid-induced Neurotoxicity in the Hippocampus in vivo.
Sehwan KIM ; Un Ju JUNG ; Yong Seok OH ; Min Tae JEON ; Hyung Jun KIM ; Won Ho SHIN ; Jungwan HONG ; Sang Ryong KIM
Experimental Neurobiology 2017;26(5):266-277
Silibinin, an active constituent of silymarin extracted from milk thistle, has been previously reported to confer protection to the adult brain against neurodegeneration. However, its effects against epileptic seizures have not been examined yet. In order to investigate the effects of silibinin against epileptic seizures, we used a relevant mouse model in which seizures are manifested as status epilepticus, induced by kainic acid (KA) treatment. Silibinin was injected intraperitoneally, starting 1 day before an intrahippocampal KA injection and continued daily until analysis of each experiment. Our results indicated that silibinin-treatment could reduce seizure susceptibility and frequency of spontaneous recurrent seizures (SRS) induced by KA administration, and attenuate granule cell dispersion (GCD), a morphological alteration characteristic of the dentate gyrus (DG) in temporal lobe epilepsy (TLE). Moreover, its treatment significantly reduced the aberrant levels of apoptotic, autophagic and pro-inflammatory molecules induced by KA administration, resulting in neuroprotection in the hippocampus. Thus, these results suggest that silibinin may be a beneficial natural compound for preventing epileptic events.
Adult
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Animals
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Brain
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Dentate Gyrus
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Epilepsy
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Epilepsy, Temporal Lobe
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Hippocampus*
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Humans
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Kainic Acid
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Mice
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Milk Thistle
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Neuroprotection
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Seizures
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Silymarin
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Status Epilepticus
2.Morin Prevents Granule Cell Dispersion and Neurotoxicity via Suppression of mTORC1 in a Kainic Acid-induced Seizure Model.
Ji Min LEE ; Jungwan HONG ; Gyeong Joon MOON ; Un Ju JUNG ; So Yoon WON ; Sang Ryong KIM
Experimental Neurobiology 2018;27(3):226-237
An abnormal reorganization of the dentate gyrus and neurotoxic events are important phenotypes in the hippocampus of patients with temporal lobe epilepsy (TLE). The effects of morin, a bioflavonoid constituent of many herbs and fruits, on epileptic seizures have not yet been elucidated, though its beneficial effects, such as its anti-inflammatory and neuroprotective properties, are well-described in various neurodegenerative diseases. In the present study, we investigated whether treatment with morin hydrate (MH) can reduce the susceptibility to seizures, granule cell dispersion (GCD), mammalian target of rapamycin complex 1 (mTORC1) activity, and the increases in the levels of apoptotic molecules and inflammatory cytokines in the kainic acid (KA)-induced seizure mouse model. Our results showed that oral administration of MH could reduce susceptibility to seizures and lead to the inhibition of GCD and mTORC1 activity in the KA-treated hippocampus. Moreover, treatment with MH significantly reduced the increased levels of apoptotic signaling molecules and pro-inflammatory mediators in the KA-treated hippocampus compared with control mice, suggesting a neuroprotective role. Therefore, these results suggest that morin has a therapeutic potential against epilepsy through its abilities to inhibit GCD and neurotoxic events in the in vivo hippocampus.
Administration, Oral
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Animals
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Cytokines
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Dentate Gyrus
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Epilepsy
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Epilepsy, Temporal Lobe
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Fruit
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Hippocampus
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Humans
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Kainic Acid
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Mice
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Neurodegenerative Diseases
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Neuroprotection
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Phenotype
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Seizures*
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Sirolimus