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Young Woo Lee,
Dong Hyun Kim,
Su Jin Jeon,
Se Jin Park,
Jong Min Kim, Jun Man Jung,
Hyung Eun Lee,
Shin Gil Bae,
Hee Kyong Oh,
Kun Ho Son,
Jong Hoon Ryu
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ABSTRACT: Salvianolic acid B (SalB) is a polyphenolic compound found in Salvia miltiorrhiza Bunge that has several anti-oxidative and anti-inflammatory effects. In the present study, we investigated whether SalB has neuroprotective effects in an amyloid β (Aβ) peptide-induced Alzheimer's disease mouse model. Mice were injected with Aβ25-35 peptide intracerebroventricularly and were subsequently administered SalB once daily for 7 days. Subchronic SalB administration (10mg/kg) significantly ameliorated the Aβ25-35 peptide-induced memory impairment in the passive avoidance task (P<0.05). SalB treatment also reduced the number of activated microglia and astrocytes that were observed during the inflammatory reaction after the administration of the Aβ25-35 peptide. Moreover, SalB markedly reduced inducible nitric oxide synthase and cyclooxygenase-2 expression levels and thiobarbituric acid reactive substances, which were increased by the administration of the Aβ25-35 peptide. Furthermore, SalB administration significantly rescued the Aβ25-35 peptide-induced decrease of choline acetyltransferase and brain-derived neurotrophic factor protein levels. These results suggest that SalB exerts neuroprotective activity via anti-inflammatory and anti-oxidative effects and that SalB may be a potential candidate for Alzheimer's disease therapy.
European journal of pharmacology 02/2013; · 2.59 Impact Factor
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Se Jin Park,
Se Jin Jeon,
Ike C Dela Peña,
Hyung Eun Lee,
Dong Hyun Kim,
Jong Min Kim,
Young Woo Lee, Jun Man Jung,
Bum Young Shin,
Seungheon Lee,
Jae Hoon Cheong,
Chan Young Shin,
Dae Sik Jang,
Jong Hoon Ryu
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ABSTRACT: Prunella vulgaris var. lilacina is widely distributed in Korea, Japan, China, and Europe, and it has been traditionally used to treat inflammation or hypertension. In the present study, we investigated the effects of the ethanolic extract of the spikes of Prunella vulgaris var. lilacina (EEPV) on dizocilpine (MK-801)-induced schizophrenia-like phenotype behaviors such as the disruption of prepulse inhibition and attention deficits in mice. We also determined the effect of EEPV on MK-801-induced alterations in phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, phospho-glycogen synthase kinase 3-β, and phosphorylated cAMP response element-binding protein levels in the cortex and hippocampus of mice. MK-801-induced prepulse inhibition deficits were ameliorated by the administration of EEPV, as shown in the acoustic startle response test. Furthermore, EEPV attenuated the MK-801-induced attention deficits in the water finding test. We also found that EEPV attenuated the increased phosphorylated extracellular signal-regulated kinase, phosphorylated protein kinase B, or phospho-glycogen synthase kinase 3-β levels induced by MK-801 in the cortex but not in the hippocampus. These results suggest that EEPV could be useful for treating schizophrenia because EEPV ameliorates prepulse inhibition disruption and attention deficits induced by MK-801. Copyright © 2013 John Wiley & Sons, Ltd.
Phytotherapy Research 01/2013; · 2.09 Impact Factor
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Hyung Eun Lee,
Dong Hyun Kim,
Se Jin Park,
Jong Min Kim,
Young Woo Lee, Jun Man Jung,
Chang Hwan Lee,
Jin Gyu Hong,
Xiaotong Liu,
Mudan Cai,
Keon Ju Park,
Dae Sik Jang,
Jong Hoon Ryu
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ABSTRACT: Sinapic acid (SA) is a phenylpropanoid compound with anti-inflammatory and neuroprotective activities. The neuroprotective effects of SA in a mouse model of amyloid β (Aβ)(1-42) protein-induced Alzheimer's disease (AD) were investigated. Mice received a bilateral injection of Aβ(1-42) protein into the hippocampus to verify the efficacy of SA. Mice were treated with SA (10mg/kg/day, p.o.) for 7days beginning immediately after Aβ(1-42) protein injection, and an acquisition trial of the passive avoidance task was conducted 1h after the last administration of SA. Retention trial was conducted 24h after the acquisition trial, and mice were sacrificed for immunohistochemistry immediately after the retention trial. SA rescued neuronal cell death in the hippocampal CA1 region and also attenuated the increase of iNOS expression, glial cell activations and nitrotyrosine expressions induced by Aβ(1-42) protein. SA significantly attenuated memory impairment in the passive avoidance task. These results suggest that SA ameliorated Aβ(1-42) protein-related pathology including neuronal cell death and cognitive dysfunction via its anti-oxidative and anti-inflammatory activities, and may be an efficacious treatment for AD.
Pharmacology Biochemistry and Behavior 08/2012; 103(2):260-266. · 2.53 Impact Factor
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Se Jin Park, Jun Man Jung,
Hyung Eun Lee,
Young Woo Lee,
Dong Hyun Kim,
Jong Min Kim,
Jin Gyu Hong,
Chang Hwan Lee,
In Ho Jung,
Yong-Baik Cho,
Dae Sik Jang,
Jong Hoon Ryu
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ABSTRACT: Alzheimer's disease is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death. INM-176 is a standardized ethanolic extract of Angelica gigas Nakai that has been traditionally used in herbal medicine in China, Japan, and Korea to treat anemia or as a sedative. We investigated whether INM-176 exhibits anti-amnesic effects.
Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist, or amyloid β(1-42) (Aβ(1-42)) protein. Anti-amnesic effects of INM-176 were measured by the passive avoidance and the Morris water maze tasks in mice. We also examined the effect of INM-176 on the acetylcholinesterase activity, as well as Aβ(1-42) protein-induced astrogliosis or cholinergic neuronal loss in the brain.
Scopolamine-induced cognitive dysfunction was significantly attenuated by a single or sub-chronic administration of INM-176 in the passive avoidance and the Morris water maze tasks. A single or sub-chronic administration of INM-176 also ameliorated memory impairments induced by Aβ(1-42) protein. INM-176 inhibited acetylcholinesterase activity in the hippocampal tissue in vitro and ex vivo. In addition, INM-176 attenuated the Aβ(1-42) protein-induced astrocyte activation in the hippocampus as well as cholinergic neuronal damage in the CA3 region of the hippocampus and the nucleus basalis of Meynert.
These results suggest that the memory ameliorating effects of INM-176 on scopolamine- or Aβ(1-42) protein-induced memory impairment are mediated, in part, via acetylcholinesterase inhibition and neuroprotective activities.
Journal of ethnopharmacology 07/2012; 143(2):611-20. · 2.32 Impact Factor
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ABSTRACT: Neuroinflammation plays a critical role in the etiology of chronic neurodegenerative diseases such as Alzheimer's disease. INM-176 is a standardized ethanolic extract of Angelica gigas, which has been traditionally used as a tonic to treat anemia. In the present study, we investigated whether INM-176 exhibits neuroprotective activities against lipopolysaccharide (LPS)-induced neuronal damage in vitro and in vivo. In primary microglial cells, INM-176 significantly inhibited LPS-induced nitric oxide release and expression of tumor necrosis factor-α and interleukin-1β. The expression levels of inducible nitric oxide synthase and cylcooxygenase-2 in BV2 microglial cells were markedly upregulated by LPS, but this increased expression was counteracted by INM-176. LPS-mediated neuronal damage in an organotypic hippocampal slice culture was also attenuated by the administration of INM-176. In addition, LPS (1 μg/2 μl, i.c.v.)-induced cognitive dysfunction in mice, as determined by passive avoidance and Y-maze tasks, was significantly attenuated by the administration of INM-176. Furthermore, the activation of microglia or astrocytes by LPS in the hippocampal regions of mice was suppressed by INM-176. These results suggest that the neuroprotective and cognition ameliorating effects of INM-176 against LPS-induced damage are mediated, in part, by its anti-inflammatory activities.
Pharmacology Biochemistry and Behavior 02/2012; 101(3):427-33. · 2.53 Impact Factor
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ABSTRACT: Stigmasterol, a kind of phytosterol, is present in small amounts in various foods. In the present study, we investigated the effects of stigmasterol on scopolamine-induced memory impairments using the passive avoidance and the Morris water maze tasks in mice. In addition, changes in memory-related molecules, including extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB), were examined following the administration of stigmasterol. Scopolamine-induced memory impairments were significantly attenuated by the administration of stigmasterol (10mg/kg) in the passive avoidance task. In the Morris water maze task, the escape latencies were significantly decreased in the stigmasterol-treated group compared to the scopolamine-treated group during the training phase. The swimming times within the target zone during the probe trial were significantly increased as compared to scopolamine-treated mice. Furthermore, the ameliorating effect of stigmasterol on scopolamine-induced memory dysfunction was blocked by a sub-effective dose of dizocilpine (MK-801), an NMDA receptor antagonist, and tamoxifen, an estrogen receptor antagonist, in the passive avoidance task. In addition, the expression levels of phosphorylated ERK and CREB in the hippocampus were significantly increased by stigmasterol, which was blocked by tamoxifen or MK-801 with scopolamine. These results suggest that stigmasterol-induced cognitive ameliorative effects are mediated by the enhancement of cholinergic neurotransmission system via the activation of estrogen or NMDA receptors.
European journal of pharmacology 12/2011; 676(1-3):64-70. · 2.59 Impact Factor
