Eun Ju Jeong

Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice

The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2 mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2 mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms.

Neuroprotective and anti-inflammatory effects of flavonoids isolated from Rhus verniciflua in neuronal HT22 and microglial BV2 cell lines

The neuroprotective and anti-inflammatory activities of the methanolic extract of Rhus verniciflua Stokes (Anacardiaceae) were investigated with mouse hippocampal and microglial cells. Bioactivity-guided isolation yielded 10 flavonoids including fustin (1), fisetin (2), sulfuretin (3), butein (4), butin (5), eriodictyol (6), morin hydrate (7), quercetin (8), kaempferol (9) and isoliquiritigenin (10). Among the isolated flavonoids, compounds 2-5 significantly protected the murine hippocampal HT22 cells against glutamate-induced neurotoxicity and attenuated reactive oxygen species (ROS) generations. In addition, these flavonoids significantly maintained antioxidative defense systems preserving the activities of superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GSH-Px) and the content of glutathione (GSH) decreased by glutamate insult. These compounds also showed significant inhibitory effects on LPS-induced nitric oxide (NO) production in BV2 cells. Especially, compound 4 dose-dependently suppressed the expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results suggest that these flavonoids possess therapeutic potentials as a multipotent agent against neurodegenerative diseases related to oxidative stress and pathological inflammatory responses.

The effects of lignan-riched extract of Shisandra chinensis on amyloid-β-induced cognitive impairment and neurotoxicity in the cortex and hippocampus of mouse.

ETHNOPHARMACOLOGICAL RELEVANCE The fruits of Schisandra chinensis (Trucz.) Baill. (Schisandraceae) which have been used as a tonic especially for kidney yin deficiency in Chinese traditional medicine are recently receiving attention for its preventive activity on age-related neurodegenerative diseases. A variety of studies demonstrated the cognitive-enhancing effects of Schisandra chinensis through animal tests and also in clinical trials. AIM OF STUDY In this study, we attempted to investigate the effects of the lignan-riched extract of Schisandra chinensis fruits (ESP-806) on neurotoxicity and memory impairment induced by Aβ1-42 injection in mice. MATERIALS AND METHODS The fruits of Schisandra chinensis were extracted with the mixture of n-hexane:ethanol (9:1), which is riched with bioactive dibenzocyclooctadiene lignans, schizandrin, gomisin N, wuweigisu C. After oral treatment of ESP-806 (100 mg/kg body weight) followed by injection of Aβ1-42 (2 μg/mouse, i.c.v.), novel object recognition and passive avoidance tests were evaluated. To verify the cognition enhancing effects of ESP-806, we examined the effects of ESP-806 on the activities of β-secretase and acetylcholinesterase, and the contents of Aβ and the reduced glutathione within the cortex and hippocampus of Aβ-injected mice. RESULTS Oral treatment of ESP-806 (100 mg/kg body weight) significantly attenuated Aβ1-42-induced memory impairment evaluated by behavioral tests. Furthermore, the treatment of ESP-806 attenuated the elevation of β-secretase activity accompanying the reduced level of Aβ1-42 in the cortex and hippocampus of the brain. ESP-806 also significantly inhibited the acetylcholinesterase activity in the hippocampus and increased the content of the reduced glutathione in the cortex and hippocampus of mouse brain. CONCLUSIONS These data suggested that the extract of Schisandra chinensis fruits riched with dibenzocyclooctadiene lignans may be useful in the prevention and treatment of Alzheimers disease.

Neuroprotective iridoid glycosides from Cornus officinalis fruits against glutamate-induced toxicity in HT22 hippocampal cells.

The methanolic extract of the fruits of Cornus officinalis S et Z. (Cornaceae) showed the significant neuroprotective activity against glutamate-induced toxicity in HT22 hippocampal cells. Chemical profile of n-BuOH fraction of the methanolic extract of C. officinalis fruits, which showed the most potent activity, was established using HPLC-diode array detector-electrospray-MS (HPLC-DAD-ESI-MS). Through bioactivity-guided isolation, five iridoid glycosides including one new compound, 7-O-butylmorroniside (1), loganin (2), morroniside (3), 7R-O-methylmorroniside (4), 7S-O-methylmorroniside (5) were isolated from the n-BuOH fraction. The protective activities of the isolated compounds, themselves, were not statistically significant. However, the hydrolyzed products of compounds 1, 4 and 5 significantly protected glutamate-injured HT22 cells up to 78±2.2%, 60±3.2% and 59±2.5% of non-treated control, respectively.

KD-501, a standardized extract of Scrophularia buergeriana has both cognitive-enhancing and antioxidant activities in mice given scopolamine

AIM OF THE STUDY The cognitive-enhancing and antioxidant activities of KD-501, a standardized extract of the roots of Scrophularia buergeriana Miquel (Scrophulariceae) were investigated. MATERIALS AND METHODS KD-501 was orally administered to amnesic mice induced by scopolamine and we performed passive avoidance and the Morris water maze tests. To elucidate the mechanism of cognitive-enhancing activity, the effects of KD-501 on the activities of acetylcholinesterase and antioxidant enzymes within the cortex and hippocampus of mice were evaluated. RESULTS Acute and prolonged oral administration of KD-501 significantly ameliorated scopolamine-induced amnesia in passive avoidance test. In the Morris water maze test, acute and prolonged administration of KD-501 improved the impairment of spatial memory induced by scopolamine indicated by the formation of reference and working memories. The activity of acetylcholinesterase was significantly inhibited by KD-501 within the cortex and hippocampus. Moreover, the reduced activities or contents of glutathione reductase, superoxide dismutase (SOD) and reduced GSH within the cortex and hippocampus caused by scopolamine were elevated by the treatment of KD-501. CONCLUSIONS Taken together, it could be postulated that KD-501 may exert its potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidative actions.

Effect of Neuroprotective Flavonoids of Agrimonia eupatoria on Glutamate-Induced Oxidative Injury to HT22 Hippocampal Cells

A methanolic extract of Agrimonia eupatoria (Rosaceae) significantly attenuated glutamate-induced oxidative stress in HT22 hippocampal cells. A new flavonoid, characterized as kaempferol 3-O-β-D-(2″-O-acetyl-6″-(E)-p-coumaroyl)-glucopyranoside (2″-acetyl-tiliroside (1), was isolated from the methanolic extract of A. eupatoria stems together with nine known flavonoids. Compounds 4, 7, 8 and 9 all showed a neuroprotective effect on glutamate-induced toxicity in HT22 cells.

Persicarin from water dropwort (Oenanthe javanica) protects primary cultured rat cortical cells from glutamate‐induced neurotoxicity

The n‐BuOH fraction of O. javanica significantly protected the primary cultures of rat cortical cells exposed to glutamate. Four flavonoids yielded from this fraction through bioactivity‐guidance. The isolated compounds, identified as isorhamnetin (1), afzelin (2), hyperoside (3) and persicarin (4), were evaluated in vitro for their neuroprotective activity. Persicarin (4), the main constituent of O. javanica, showed significant neuroprotective activities in glutamate‐injured rat cortical cells. Persicarin diminished calcium influx and inhibited the subsequent overproduction of nitric oxide and intracellular peroxide. In addition, persicarin significantly restored the reduced activities of glutathione (GSH) reductase and glutathione peroxidase, and the contents of GSH induced by glutamate. These results support a conclusion that persicarin greatly contributes to the neuroprotective activities of O. javanica. Copyright

Development of dried liposome as effective immuno-adjuvant for hepatitis b surface antigen

Dried liposomes containing recombinant hepatitis B surface antigen (HBsAg) were developed to enhance the immunogenicity of HBsAg and to retain the stability of liposomal HBsAg during storage. Vesicles containing HBsAg were prepared by extruding the dehydration-rehydration vesicles with entrapped HBsAg through 400 nm polycarbonate filter. The sized liposomes were lyophilized in the presence of trehalose (4 g/g lipid) as a cryopreservative. Dried liposomes were rehydrated in distilled water with brief vortexing prior to use. When rehydrating the dried liposomes after 1 year of storage at 4°C, the vesicles showed a size distribution similar to that obtained before lyophilization, and retained about 70% of HBsAg immunogenicity. Dried liposomes containing HBsAg showed significantly earlier sero-conversion (p < 0.05) and higher titre compared to the free HBsAg and the mixture of HBsAg and aluminum phosphate. Taken together, these results suggest that the dried liposomes, with high stability and enhanced immunogenicity, can be further developed as potential immuno-adjuvants for HBsAg.

Antifibrotic activity of diterpenes from Biota orientalis leaves on hepatic stellate cells

Antifibrotic effect of twelve diterpenes (1–12) from the 90% methanolic fraction of Biota orientalis leaves was evaluated employing HSC-T6 cells by assessing cell proliferation and morphological change. Among these diterpenes, totarol (8) and isopimara-8(14),15-dien-19-oic acid (9) dramatically reduced cell proliferation in dose-and time-dependent manner. Furthermore, treatment with these compounds resulted in the different pattern of morphological changes of HSC-T6 cells. Taken together, antiproliferative activity of diterpenes from B. orientalis might suggest therapeutic potentials against liver fibrosis.

Anti-inflammatory phenolics isolated from Juniperus rigida leaves and twigs in lipopolysaccharide-stimulated RAW264.7 macrophage cells.

Inflammation is an essential host defense system particularly in response to infection and injury; however, excessive or undesirable inflammatory responses contribute to acute and chronic human diseases. A high-throughput screening effort searching for anti-inflammatory compounds from medicinal plants deduced that the methanolic extract of Juniperus rigida S. et L. (Cupressaceae) inhibited significantly nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Activity-guided fractionation and isolation yielded 13 phenolic compounds, including one new phenylpropanoid glycosides, 3,4-dimethoxycinnamyl 9-O-β-D-glucopyranoside (1). Among the isolated compounds, phenylpropanoid glycosides with p-hydroxy group (2, 4) and massoniaside A (7), (+)-catechin (10), amentoflavone (11) effectively inhibited LPS-induced NO production in RAW264.7 cells.