Ji-Wook Jung

Direct pharmacological Akt activation rescues Alzheimer's disease like memory impairments and aberrant synaptic plasticity

ABSTRACT Amyloid &bgr; (A&bgr;) is a key mediator for synaptic dysfunction and cognitive impairment implicated in Alzheimers disease (AD). However, the precise mechanism of the toxic effect of A&bgr; is still not completely understood. Moreover, there is currently no treatment for AD. Protein kinase B (PKB, also termed Akt) is known to be aberrantly regulated in the AD brain. However, its potential function as a therapeutic target for AD‐associated memory impairment has not been studied. Here, we examined the role of a direct Akt activator, SC79, in hippocampus‐dependent memory impairments using A&bgr;‐injected as well as 5XFAD AD model mice. Oligomeric A&bgr; injections into the 3rd ventricle caused concentration‐dependent and time‐dependent impairments in learning/memory and synaptic plasticity. Moreover, A&bgr; aberrantly regulated caspase‐3, GSK‐3&bgr;, and Akt signaling, which interact with each other in the hippocampus. Caspase‐3 and GSK‐3&bgr; inhibitor ameliorated memory impairments and synaptic deficits in A&bgr;‐injected AD model mice. We also found that pharmacological activation of Akt rescued memory impairments and aberrant synaptic plasticity in both A&bgr;‐treated and 5XFAD mice. These results suggest that Akt could be a therapeutic target for memory impairment observed in AD. HIGHLIGHTSOligomeric A&bgr; impaired learning and memory and synaptic plasticity.Caspase inhibition ameliorated A&bgr;‐induced deficits.Akt activation ameliorated A&bgr;‐induced deficits.GSK‐3&bgr; inhibition ameliorated A&bgr;‐induced deficits.Akt activation ameliorated learning and memory and synaptic deficits in 5XFAD mice.

The Ameliorative Effect of Sophoricoside on Mast Cell-Mediated Allergic Inflammation in Vivo and in Vitro

Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases.

Anxiolytic-like effects of Portulaca oleraceae L. using the elevated plus-maze in mice

SUMMARY The purpose of this study was to characterize the putative anxiolytic-like effects of the 70%ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPOwas orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioralevaluation in the EPM, respectively. Control mice were treated with an equal volume of 10%tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPOsignificantly increased the percentage of time spent and arm entries into the open arms of theEPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity andmyorelaxant effects in any group compared with the saline controls. In addition, the anxiolytic-like effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a GABA A antagonist not byWAY 100635 (0.3 mg/kg, i.p), a 5-HT 1A receptor antagonist. These results indicate that P. oleraceais an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea ismediated via the GABAergic nervous system.Key words: Anxiety; Portulaca oleracea; Elevated plus-maze; WAY 100635; Flumazenil

Ribes fasciculatum var. chinense Attenuated Allergic Inflammation In Vivo and In Vitro

Ribes fasciculatum var. chinense MAX. (R. fasciculatum) has traditionally been used in Korea to treat inflammatory diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of R. fasciculatum is not completely understood. We aimed to ascertain the pharmacological effects of R. fasciculatum on both compound 48/80- or histamine-induced scratching behaviors and 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of R. fasciculatum, we evaluated the effects of R. fasciculatum on the production of inflammatory mediators in LPS-stimulated macrophage cells. Treatment of R. fasciculatum significantly reduced compound 48/80- or histamine-induced the pruritus in mice. R. fasciculatum attenuated the AD symptoms such as eczematous, erythema and dryness and serum IgE levels in AD model. Additionally, R. fasciculatum inhibited the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The maximal rates of TNF-α and IL-6 inhibition by R. fasciculatum (1 mg/ml) were approximately 32.12% and 46.24%, respectively. We also showed that R. fasciculatum inhibited the activation of nuclear factor-kappa B in LPS-stimulated macrophages. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of R. fasciculatum as a potential molecule for use in the treatment of allergic inflammatory diseases.

Betula platyphylla attenuated mast cell-mediated allergic inflammation in vivo and in vitro.

AIMSnBetula platyphylla (B. platyphylla) has traditionally been used in Korea to treat inflammatory diseases. However, the exact mechanism that accounts for the anti-inflammatory effect of B. platyphylla is not completely understood. The aim of the present study is to elucidate whether and how B. platyphylla modulates the mast cell-mediated allergy inflammation in vitro and in vivo.nnnMAIN METHODSnWe investigated to ascertain the pharmacological effects of B. platyphylla on both compound 48/80 or histamine-induced scratching behaviors and 2, 4-dinitrochlrobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of B. platyphylla, we evaluated the effects of B. platyphylla on the release of histamine in compound 48/80-induced rat peritoneal mast cells (RPMCs), production of inflammatory mediators and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1).nnnKEY FINDINGSnThe finding of this study demonstrated that B. platyphylla reduced compound 48/80 or histamine-induced scratching behaviors and DNFB-induced atopic dermatitis in mice. Additionally, B. platyphylla inhibited the release of histamine in RPMC and production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1.nnnSIGNIFICANCEnCollectively, the findings of this study provide us with novel insights into the pharmacological actions of B. platyphylla as a potential molecule for use in the treatment of allergic inflammatory diseases.

Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

OBJECTIVEnTo investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai (AGNE) on dextran sulfate sodium (DSS)-induced murine ulcerative colitis (UC).nnnMETHODSnThe therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-α, PGE2, COX-2 and HIF-1α were assayed by enzyme-linked immunosorbent assay or western blotting.nnnRESULTSnTreatment with the AGNE at 10, 20, and 40xa0mg/kg alleviated weight loss, decreased disease activity index scores, and reduced colon shortening in mice with DSS-induced UC. AGNE inhibited the production of IL-6 and TNF-α in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1α and the increased production of PGE2 in colon tissue were observed in mice with DSS-induced UC. Additionally, histological damage was also alleviated by AGNE treatment.nnnCONCLUSIONSnThe findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

Fragrant Chemicals in the Supercritical Carbon Dioxide Extract of Magnolia kobus DC. Flower Buds Increase the Concentration State of Brain Function

Abstract In traditional Korean medicine, flower buds of Magnolia kobus DC. plant is widely used for the treatments of various disorders. Hence, the present study was undertaken to evaluate the effect of supercritical carbon dioxide extract (SFE) of M. kobus flower buds on electroencephalographic (EEG) changes of human brain. The extract from the flower buds of M. kobus was obtained by SFE and the yield was 0.27% at 40°C and 400 bar pressure. Subsequently, GC-MS analysis revealed that the major components of the SFE were caryophyllene (19.93%) and α-terpineol (12.49%). A large proportion of the oil was composed in the groups of hydrocarbons (55.09%) and alcohols (31.21%). In addition, fragrance evaluation of extract of M. kobus flower buds showed the characteristics of balsamic, floral, herbal, medicinal, minty, oily and spicy. In EEG study, the data were observed before and during the inhalation of M. kobus fragrance. During the inhalation of M. kobus fragrance, the EEG power spectrum values of absolute theta and alpha decreased in all the frontal, temporal and parietal regions. A significant decrease (pu2009<u20090.05) of absolute alpha wave was observed at left parietal (P3) region. The results reveal that the changes in EEG values to awaken and increase the concentration states of brain. The present investigation clearly suggested that the fragrance of M. kobus flower buds could be attributed to the enhancement of psychophysiological activities of human.

Fragrance Chemicals in the Essential Oil of Mentha arvensis Reduce Levels of Mental Stress

The aim of this work was to determine the chemical composition of essential oil from aerial partsof Mentha arvensis L. f. piperascens (MAO) and to evaluate the effect of its fragrant chemicals on electroencephalographic (EEG) activity of human brain. The MAO was obtained by supercritical CO2 extraction. The maximum yield was 2.38% at conditions of 70oC and 200 bar. There were 32 volatile chemicals with 6 alcohols (67.11%), 13 hydrocarbons (17.05%), 9 esters (11.50%), 2 ketones (7.16%), 1 oxide (2.77%), and 1 aldehyde (0.56%). The major components were (Z,Z,Z)-9,12,15-octadecatrien-1-ol (50.06%), 2-hydroxy-4-methoxyacetophenone (7.50%), and 3,4-dihydro-8-hydroxy-3-methyl-1H-2-benzopyran- 1-one (6.60%). Results of the EEG study showed that inhalation of MAO significantly changed the EEG power spectrum values of relative gamma, relative fast alpha, and spectral edge frequency 90%. During the inhalation of MAO, the value of relative fast alpha was significantly increased (p<0.05). On the other hand, the values of gamma and the spectral edge frequency 90% were significantly decreased (p<0.05). The present study suggests that fragrant chemicals of essential oil of M. arvensis reduce the level of mental stress and that they could be used in the treatment of psychophysiological disorders.

Effect of Essential Oil from San-Jo-In (Zizyphus jujuba Mill. seeds) on Human Electroencephalographic Activity

Essential oils have been used to treat psychophysiological disorders, but their effects on human electroencephalographic (EEG) activity have not been thoroughly investigated. We evaluated the effects of essential oil of Zizyphus jujuba seeds, a Korean folk medicine known as San-Jo-In, on human EEG activity. For this purpose, essential oil was extracted from San-Jo-In by the supercritical carbon dioxide extraction method. The effect of its inhalation on EEG activity was evaluated by measuring the EEG power spectrum (25 indices) in 20 healthy participants. The results of the EEG power spectrum indicated that the values of the theta wave decreased significantly (p<0.05) in the left (from 17.277 to 13.854 μV) and right parietal (from 15.324 to 13.020 μV) regions compared to the other regions. During the inhalation of San-Jo-In oil, the EEG spectrum values of fast alpha, relative gamma, and spectral edge frequency increased 50% compared to those before inhalation. The values of the fast alpha wave increased significantly (p<0.05) in the left prefrontal (from 0.063 to 0.085 μV), right prefrontal (from 0.064 to 0.085 μV), and left frontal (from 0.073 to 0.100 μV) regions following inhalation of the San-Jo-In essential oil. The changes in the EEG activities following inhalation of San-Jo-In suggest that the oil can improve psychological well-being by increasing attention and relaxation.

Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling

Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3β mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Akt blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3β blocked the natural decline in LTP. These results demonstrate that GSK-3β might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Akt/GSK-3β signaling.