• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.5
• /
• pp.279-283
• /
• 2010

Urushinol, a plant allergen, has significantly restricted the medical application of $Rhus$ $verniciflua$, although it has been reported to possess a wide variety of biological activities such as anti-inflammatory, antioxidant, and anti-cancer actions. To reduce the urushinol content while maintaining the beneficial biological activities, mushroom-mediated fermentation of $Rhus$ $verniciflua$ was carried out and this method resulted in significantly attenuated allergenicity [1]. In the present study, to examine the neuroprotective properties of mushroom-fermented stem bark of $Rhus$ $verniciflua$, two constituents were isolated from mushroom-fermented bark and their neuroprotective properties were examined in a mouse model of kainic acid (KA)-induced excitotoxicity. KA resulted in significant apoptotic neuronal cell death in the CA3 region of mouse hippocampus. However, seven daily administrations of RVH-1 or RVH-2 prior to KA injection significantly attenuated KA-induced pyramidal neuronal cell death in the CA3 region. Furthermore, pretreatment with RVH-1 and RVH-2 also suppressed KA-induced microglial activation in the mouse hippocampus. The present study demonstrates that RVH-1 and RVH-2 isolated from $Rhus$ $verniciflua$ and detoxified using mushroom species possess neuroprotective properties against KA-induced excitotoxicity. This leads to the possibility that detoxified $Rhus$ $verniciflua$ can be a valuable asset in herbal medicine.

• Clinical and Experimental Pediatrics
• /
• v.45 no.12
• /
• pp.1551-1558
• /
• 2002

Purpose : Loss of hippocampal interneurons in dentate gyrus has been reported in patients with severe temporal lobe epilepsy and in animals treated with kainic acid(KA). Interneurons contain $Ca^{2+}$- binding protein parvalbumin(PV). The effects of kainic acid on parvalbumin-immunoreactive (PV-IR) interneurons in dentate gyrus were investigated in organotypic hippocampal slice cultures. Methods : Cultured hippocampal slices from postnatal day nine C57/BL6 mice were exposed to $10{\mu}M$ KA, and were observed at 0, 8, 24, 48, 72 hours after a one hour KA exposure. Neuronal injury was determined by morphologic changes of PV-IR interneuron in dentate gyrus. Results : Transient(1 hour) exposure of hippocampal explant cultures to KA produced marked varicosities in dendrites of PV-IR interneuron in dentate gyrus and the shaft of interbeaded dendrite is often much thinner than those in control. The presence of varicosities in dendrites was reversible with KA washout. The dendrites of KA treated explants were no longer beaded at 8, 24, 48 and 72 hours after KA exposure. The number of cells in PV-IR interneurons in dentate gyrus was decreased at 0, 8 hours after exposure. But there was no significant difference in 24, 48 and 72 hours recovery group compared with control group. Conclusion : The results suggested that loss of PV-IR interneurons in dentate gyrus is transient, and is not accompanied by PV-IR interneuronal cell death.

• Natural Product Sciences
• /
• v.9 no.4
• /
• pp.249-255
• /
• 2003

Zizypus is one of the herbs widely used in Korea and China due to CNS calming effect. The present study aims to investigate the effect of the methanol extract of Zizyphi Jujube Semen (ZJS) on kainic acid (KA)-induced neurotoxicity in cultured rat cerebellar granule neuron. ZJS, over a concentration range of 0.05 to $5\;{\mu]g/ml$, inhibited KA $(500\;{\mu}M)-induced$ neuronal cell death, which was measured by a trypan blue exclusion test and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. Pretreatment of ZJS $(0.5\;{\mu}g/ml)$ inhibited KA$(50\;{\mu}M)$-induced elevation of cytosolic calcium concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, Fura 2-AM, and generation of reactive oxygen species (ROS). ZJS $(0.5\;{\mu}g/ml)$ inhibited glutamate release into medium induced by KA $(500\;{\mu}M)$, which was measured by HPLC. These results suggest that ZJS prevents KA-induced neuronal cell damage in vitro.

• The Korean Journal of Physiology and Pharmacology
• /
• v.5 no.6
• /
• pp.451-456
• /
• 2001

In rat hippocampus, kainic acid (KA; 10 mg/kg; i.p.) increased the phosphorylated forms of ERK1/2 (p-ERK1/2) and Jun kinase1 (p-JNK1), but not p-JNK2 and p38 (p-p38). The preadministration with cycloheximide (CHX; 5 mg/kg; i.p.) inhibited KA-induced increase of p-JNK1, but not p-ERK1/2. Surprisingly, the phosphorylated upstream MAP kinase kinases (p-MKKs) were not correlated with their downstream MAP kinases. The basal p-MKK1/2 levels were completely abolished by KA, which were reversed by CHX. In addition, p-MKK4 and p-MKK3/6 levels were enhanced by CHX alone, but were attenuated by KA. Thus, our results showed that KA increased the p-ERK and p-JNK levels in rat hippocampus, which were not parallel with their classical upstreamal kinases.

• Korean Journal of Acupuncture
• /
• v.24 no.4
• /
• pp.99-110
• /
• 2007

Objectives : Epilepsy is one of the most common serious brain disorders that affect people of all ages, and it is characterized by recurrent unprovoked seizures. We examined whether acupuncture can reduce both the incidence of seizures and hippocampal cell death in dentate gyrus (DG) using a mouse model of kainic acid (KA)-induced epilepsy. Methods : ICR mice ($20{\sim}25$ g) were given acupuncture once a day at acupoint HT8 (sobu) bilaterally during 2 days before KA injection. After an intracerebroventricular injection of 0.1${\mu}g$ of KA, acupuncture treatment was subsequently administered once more (total 3 times), and the degree of seizure was observed for 20 min. Three hours after injection, we confirmed the neural cell death using cresyl violet staining and silver impregnation staining, and determined the expressions of c-Fos and glutamate decarboxylase (GAD)-67 using immunohistochemistry techniques in the DG. Results : KA induced epileptic seizure, neural cell death, increased c-Fos expression and decreased GAD-67 expression in the DG. Acupuncture treatment at HT8 reduced the severity of the epileptic seizure and inhibited neural cell death from KA. In addition, acupuncture normalized the expressions of c-Fos and GAD-67 in the same areas. Conclusions : These results demonstrated that acupuncture treatment at HT8 may reduce the KA-induced epileptic seizure and neural cell death in the DG possibly by normalizing c-Fos expressions and the gamma-aminobutyric acid neurons.

• Proceedings of the Korean Society for Emotion and Sensibility Conference
• /
• 2008.10a
• /
• pp.147-150
• /
• 2008

Vitamin C ascorbic acid (AA) and dehydroascorbic acid (DHA) as an antioxidant have been shown to have protective effects in experimental neurological disorder models such as stroke, ischemia, and epileptic seizures. The present study was conducted to examine the protective effect of AA and DHA on Kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures (OHSC). After 12h KA treatment, significant delayed neuronal death was detected in CA3 region, but not in CA1. Intermediate dose of AA and DHA pretreatment significantly prevented cell death and inhibit ROS level, mitochondrial dysfunction and capase-3 activation in CA3 region. In the case of low or high dose, however, AA or DHA pretreatment were not effective. These data suggest that both AA and DHA pretreatment have neuroprotective effects on KA-induced neuronal injury depending on the concentration, by means of inhibition of ROS generation, mitochondrial dysfunction, and caspase-dependent apoptotic pathway.

• Biomolecules & Therapeutics
• /
• v.23 no.3
• /
• pp.261-267
• /
• 2015

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor ${\gamma}$ agonist, is known to regulate inflammatory process and to have neuroprotective effects against neurological disorders. In the present study, we examined the effects of 30 mg/kg PGZ on excitotoxic neuronal damage and glial activation in the mouse hippocampus following intracerebroventricular injection of kainic acid (KA). PGZ treatment significantly reduced seizure-like behavior. PGZ had the neuroprotective effect against KA-induced neuronal damage and attenuated the activations of astrocytes and microglia in the hippocampal CA3 region. In addition, MPO and $NF{\kappa}B$ immunoreactivities in the glial cells were also decreased in the PGZ-treated group. These results indicate that PGZ had anticonvulsant and neuroprotective effects against KA-induced excitotocix injury, and that neuroprotective effect of PGZ might be due to the attenuation of KA-induced activation in astrocytes and microglia as well as KA-induced increases in MPO and $NF{\kappa}B$.

• Korean Journal of Medicinal Crop Science
• /
• v.12 no.5
• /
• pp.415-423
• /
• 2004

Myristica fragrans seed from Myristica fragrans Houtt (Myristicaceae) has various pharmacological activities peripherally and centrally. The present study aims to investigate the effect of the methanol extract of Myristica fragrans seed (MF) on kainic acid (KA)-induced neurotoxicity in primary cultured rat cerebellar granule neuron. MF, over a concentration range of 0.05 to $5\;{\mu}g/ml$ inhibited KA $(500\;{\mu}M)-induced$ neuronal cell death, which was measured by trypan blue exclusion test and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. MF $(0.5\;{mu}g/ml)$ inhibited glutamate release into medium induced by KA $(500\;{\mu}M)$, which was measured by HPLC. Pretreatment of MF $(0.5\;{mu}g/ml)$ inhibited KA $(500\;{\mu}M)-induced$ elevation of cytosolic calcium concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, Fura 2-AM, and generation of reactive oxygen species (ROS). These results suggest that MF prevents KA-induced neuronal cell damage in vitro.

• BMB Reports
• /
• v.32 no.4
• /
• pp.339-344
• /
• 1999

We studied the effects of ginsenosides in immature rats based upon the previous results that ginseng has a suppressive or anticonvulsive activity. To examine the suppressive effect of ginsenosides on kainic acid-induced seizures, the severities and frequencies were observed for 4 h after injection of kainic acid (KA; i.p., 2 mg/kg b.w.) using 10-day-old male Sprague-Dawley rats ($22{\pm}2\;g$). Protopanaxadiol saponins such as ginsenoside-Rb1 (Rb1), ginsenoside-Rb2 (Rb2), ginsenoside-Rc (Rc), and ginsenoside-Rd(Rd) generally reduced the seizure activities while protopanaxatriol saponins such as ginsenoside-Rg1 (Rg1) and ginsenoside-Re (Re) rather increased stereotypic "paddling-like" movements. When vinyl-GABA (v-G) was injected together with Rb1 or Rc, KA-induced seizure severities were additionally reduced only by the injection of Rc, but not by Rb1. The level of gamma isozyme of protein kinase C (PKC-${\gamma}$) in the hippocampus increased about three times as much as that of normal rats at 4 h after KA injection. The increased level of PCK-${\gamma}$ by KA was significantly reduced to about 35% by the coinjection with v-G alone, but it was not changed by v-G together with Rb1 or Rc. The increased level of PKC-${\gamma}$ at 4 h after injection of KA was not consistent with the reduction of seizure severities between Rb1 and Rc. These results suggest that Rc and Rb1 may reduce seizure severity independent of PKC-${\gamma}$ levels, and Rc may additionally act with v-G regarding the GABA metabolism during the stage of KA-induced seizures in the immature rats.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.5
• /
• pp.257-263
• /
• 2010

Visnagin (4-methoxy-7-methyl-5H-furo[3,2-g][1]-benzopyran-5-one), which is an active principle extracted from the fruits of Ammi visnaga, has been used as a treatment for low blood-pressure and blocked blood vessel contraction by inhibition of calcium influx into blood cells. However, the neuroprotective effect of visnagin was not clearly known until now. Thus, we investigated whether visnagin has a neuroprotective effect against kainic acid (KA)-induced neuronal cell death. In the cresyl violet staining, pre-treatment or post-treatment visnagin (100 mg/kg, p.o. or i.p.) showed a neuroprotective effect on KA ($0.1{\mu}g$) toxicity. KA-induced gliosis and proinflammatory marker (IL-$1{\beta}$, TNF-${\alpha}$, IL-6, and COX-2) inductions were also suppressed by visnagin administration. These results suggest that visnagin has a neuroprotective effect in terms of suppressing KA-induced pathogenesis in the brain, and that these neuroprotective effects are associated with its anti-inflammatory effects.