Ameliorative Effect of Citrus junos Tanaka Waste (By-Product) Water Extract on Particulate Matter 10-Induced Lung Damage.

Citrus junos Tanaka (CJ)-related products are well-accepted by consumers worldwide; thus, they generate huge amounts of waste (peel, pulp, and seed) through CJ processing. Although some CJ by-products (CJBs) are recycled, their use is limited owing to the limited understanding of their nutritional and economic value. The exposure to particulate matter (PM) increases the risk of respiratory diseases. In this study, we investigated the ameliorative effects of CJB extracts (100, 200 mg/kg/day, 7 days) on PM10-induced (10 mg/kg, intranasal, 6 h) lung damage in BALB/c mice. Cell type-specific signaling pathways are examined using the A549 (PM10, 200 µg/mL, 6 h) and RAW264.7 (LPS, 100 ng/mL, 6 h) cell lines. The CJB extracts significantly attenuated PM10-induced pulmonary damage and inflammatory cell infiltration in a mouse model. The essential protein markers in inflammatory signaling pathways, such as AKT, ERK, JNK, and NF-κB for PM10-induced phosphorylation, were dramatically reduced by CJB extract treatment in both the mouse and cell models. Furthermore, the CJB extracts reduced the production of reactive oxygen species and nitric oxide in a dose-dependent manner in the cells. Comprehensively, the CJB extracts were effective in reducing PM10-induced lung injuries by suppressing pulmonary inflammation, potentially due to their anti-inflammatory and antioxidant properties.

Xanthorrhizol Suppresses Vascular Endothelial Growth Factor-Induced Angiogenesis by Modulating Akt/eNOS Signaling and the NF-[Formula: see text]B-Dependent Expression of Cell Adhesion Molecules.

Angiogenesis plays a crucial role in tumor growth and metastasis. Vascular endothelial growth factor (VEGF)-stimulated endothelial cell proliferation and migration are critical steps in tumor angiogenesis. Here, we investigated the anti-angiogenic activity of xanthorrhizol, a sesquiterpenoid isolated from the Indonesian medicinal plant Curcuma xanthorrhiza. Xanthorrhizol at noncytotoxic concentrations inhibited the proliferation, migration, and formation of capillary-like tubes in VEGF-treated human umbilical vein endothelial cells (HUVECs). Xanthorrhizol inhibited the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) and the expression of vascular cell adhesion molecule (VCAM)-1 and E-selectin in VEGF-treated HUVECs. The expression and transcriptional activity of NF-[Formula: see text]B were downregulated by xanthorrhizol in VEGF-treated HUVECs. Furthermore, xanthorrhizol significantly inhibited VEGF-induced angiogenesis in the chorioallantoic membrane of fertilized eggs and Matrigel plugs subcutaneously injected into mice. Xanthorrhizol inhibited tumor volume and tumor-derived angiogenesis in mice inoculated with breast cancer cells. The in vitro and in vivo anti-angiogenic activities of xanthorrhizol were as potent as those of curcumin, a well-known anticancer agent derived from C. longa. Taken together, xanthorrhizol inhibits VEGF-induced angiogenesis of endothelial cells by blocking the activation of the PI3K/Akt/eNOS axis and subsequent upregulation of adhesion molecules induced by the transcriptional activation of NF-[Formula: see text]B. Xanthorrhizol is a promising anti-angiogenic agent and can serve as a beneficial agent to enhance anticancer treatments.

Ameliorative Effects of Dendropanax morbifera on Cognitive Impairment Via Enhancing Cholinergic Functions and Brain-Derived Neurotrophic Factor Expression in ß-Amyloid-Induced Mice.

Alzheimer's disease accounts for the majority of dementia and shows hallmarks such as sequential cognitive dysfunction and abnormal behavior. Dendropanax morbifera (DM) has traditionally been used to treat a variety of diseases in East Asia. The aim of this study was to assess the therapeutic effects of DM on brain neuron damage and on cognitive deficit in neuronal cell induced by Aß1-42 in mice. Treatment with DM reduced the levels of intracellular reactive oxygen species and protected against the death of neuronal cells induced by Aß1-42 peptide. In addition, it was also found that pretreatment with DM decreased cognitive damage induced by Aß peptide via enhancing the cholinergic system and antioxidant defense system in mice. Furthermore, the study verified that the change in the expression of both cyclic-adenosine monophosphate response element binding protein and of brain-derived neurotrophic factor in the hippocampus in Aß peptide-treated mice was significantly ameliorated after treatment with DM. Accordingly, these results suggest that pretreatment with DM defends against oxidative stress and cognitive impairment caused by Aß peptide.

Comparison of the Effects of Nonfermented and Fermented Panax ginseng Root Against Hypertriglycemia in High-Fat Diet-Fed Mice.

Panax ginseng (P. ginseng C.A. Meyer, Araliaceae) is used as a therapeutic agent for various diseases. P. ginseng saponins, known as ginsenosides, are the main bioactive compounds responsible for its pharmacological activities. In this work, we have developed a new method of P. ginseng root processing termed solid-state fermentation and examined its effects compared with nonfermented P. ginseng. Mice were fed a high-fat diet (HFD) to induce hyperlipidemia and then received 100 mg·kg bw-1·day-1 of fermented or nonfermented P. ginseng orally for 3 weeks. We assessed the activities of lipogenic pathways and lipid levels in the liver and plasma. The administration of either nonfermented or fermented P. ginseng improved hepatic lipid transfer protein profiles. Nonfermented P. ginseng exhibited significant effects on the regulation of lipid synthesis and oxidation. However, apolipoprotein A4 (apoA4) expression was increased by the administration of fermented P. ginseng. When ginsenosides were analyzed by high-performance liquid chromatography (HPLC), the amounts of the ginsenosides, Rg2, Rc, Rh1(S), Rh1(R), and Rd, were increased by fermentation, with Rd becoming a major constituent of fermented P. ginseng. These findings imply that nonfermented P. ginseng improves hypertriglycemia in HFD-fed mice through regulation of the hepatic lipogenic pathway. In contrast, the effects of fermented P. ginseng were mediated through increased apoA4, leading to decreased triglycerides. The HPLC profiles of ginsenosides suggest that the compositional changes in P. ginseng caused by fermentation processing could be useful in the development of novel triglyceride-lowering therapies.

Hypolipidemic and Antidiabetic Effects of Functional Rice Cookies in High-Fat Diet-Fed ICR Mice and db/db Mice.

We have previously reported the lipid-lowering effects of a Korean rice cookie called dasik (RCD) in comparison with a western style cookie. In this study, Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) fruit-supplemented RCD (SRCD) was added to a diet, and the hypolipidemic and antidiabetic effects of different diets were examined by using the ICR and db/db mouse models, respectively. ICR mice were fed the AIN-76 diet, or high-fat diet (HFD), or the RCD- or SRCD-supplemented HFD (10%, w/w) for 9 weeks (n = 7 per group). Compared with the RCD group, plasma and hepatic triglyceride and cholesterol concentrations were decreased in the SRCD group. Hepatic expressions for fatty acid and cholesterol synthesis were downregulated, whereas those for beta-oxidation and cholesterol export were upregulated (P < .05). The antidiabetic effects of SRCD were tested in db/db mice for 10 weeks (n = 7 per group). Glucose tolerance was improved in the SRCD group through the regulation of gluconeogenic enzymes and biomarkers related to the insulin signaling pathway (P < .05). In addition, SRCD increased the expression levels of antioxidative enzymes, and decreased those of inflammatory cytokines (P < .05). Moreover, oxidative stress, leptin, and insulin levels were lower in the SRCD group than in the other groups (P < .05). In conclusion, the lipid-lowering and antidiabetic effects of SRCD were greater than those of RCD with respect to the suppression of lipid synthesis, oxidative stress, and inflammation and the improvement of glucose metabolism.

Neuroprotective Effects of the Methanol Extract of Kimchi, a Korean Fermented Vegetable Food, Mediated Via Suppression of Endoplasmic Reticulum Stress and Caspase Cascade Pathways in High-Cholesterol Diet-Fed Mice.

Endoplasmic reticulum (ER) stress-related unfolded peptide accumulation is closely associated with the development of neurodegenerative diseases known as protein misfolding disorders. The antioxidative properties of kimchi, a traditional Korean fermented vegetable dish, have been well established. In this study, the neuroprotective effects of the kimchi methanol extract (KME) were examined in high-cholesterol diet (HCD)-fed mice. The animals were fed a HCD, with oral administration of either KME (KME group, 200 mg·kg bw-1·day-1, n = 10) or distilled water (Control group, n = 10) for 8 weeks. Compared with the levels in the control group, the reactive oxygen species, peroxynitrite, and lipid peroxidation levels in the brain were significantly decreased in the KME group (P < .05), whereas the glutathione level was increased (P < .05). In addition, the ER stress biomarkers, phospho-eukaryotic initiation factor 2 subunit α, glucose-regulated protein 78, X-box binding protein 1, inositol-requiring enzyme 1, and C/EBP homologous protein and the nuclear factor-kappaB-mediated inflammation were significantly reduced in the KME group (P < .05). In contrast, the expression levels of antioxidative enzymes regulated by nuclear factor erythroid 2-related factor-2 were elevated (P < .05). The amyloid-beta expression levels of the KME group were lower than that of the control group (P < .05). Moreover, the expression levels of Bcl-2-associated X, and caspases-3 and -9 were downregulated, with a concomitant upregulation of B cell lymphoma 2 (P < .05). Accordingly, KME provide neuronal cell protection via suppressing ER stress and caspase cascade signaling.

Perilla Oil Reduces Fatty Streak Formation at Aortic Sinus via Attenuation of Plasma Lipids and Regulation of Nitric Oxide Synthase in ApoE KO Mice.

Consumption of n-3 polyunsaturated fatty acids (PUFA) is associated with a reduced incidence of atherosclerosis. Perilla oil (PO) is a vegetable oil rich in α-linolenic acid (ALA), an n-3 PUFA. In this study, antiatherogenic effects and related mechanisms of PO were investigated in atherosclerotic mice. Apolipoprotein E knockout (ApoE KO) mice (male, n = 27) were fed high-cholesterol and high-fat diets containing 10 % w/w lard (LD), PO, or sunflower oil (SO) for 10 weeks. Plasma triglyceride, total cholesterol, and low-density lipoprotein cholesterol concentrations reduced in the PO and SO groups compared to the concentrations in the LD group (P < 0.05). The PO group showed reduced fatty streak lesion size at the aortic sinus (P < 0.05) compared to the sizes in the LD and SO groups. A morphometric analysis showed enhancement of endothelial nitric oxide synthase expression and reduction of inducible nitric oxide synthase expression in the PO group compared to that in the LD group (P < 0.05). Furthermore, aortic protein expression of intercellular cell adhesion molecule 1 and vascular cell adhesion molecule 1 was diminished in the PO group compared to that in the LD and SO groups (P < 0.05). These findings suggested that PO inhibited the development of aortic atherosclerosis by improving the plasma lipid profile, regulating nitric oxide synthase, and suppressing the vascular inflammatory response in the aorta of ApoE KO mice.

Superiority of traditional cooking process for bugak (Korean traditional fried dish) for plasma lipid reduction.

In this study, the efficacy and mode of action of the Korean traditional fried dish bugak for reducing plasma lipids are investigated. Three different studies were performed as follows: lipid-lowering effects of bugak compared with (1) different preparation methods, (2) different batters, and (3) different frying oils. Traditionally, bugak is prepared with fermented glutinous rice batter (FGR) and pan-fried in unroasted sesame oil (USSO; this preparation of bugak is referred to as FGRUSSO). FGR is prepared by placing the glutinous rice and water in a crock for 7 days at room temperature. For the study, wheat flour batter (WF) and soybean oil (SBO) were alternatively used. Low-density lipoprotein receptor knockout (LDLr⁻/⁻) mice (n=24) were fed atherogenic diets with bugak (20 g/100 g of feed) for 10 weeks. Plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) concentration and hepatic lipid accumulations decreased significantly in mice fed FGRUSSO, compared with bugak made with WF and fried in SBO (WFSBO). Protein expression of fatty acid synthesis (FAS) and 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMGCR) in the FGRUSSO group was decreased, although sterol regulatory element-binding proteins (SREBP-1 and -2) were not different. When batter differences were compared, TG concentration of mice fed bugak prepared with FGR and fried in SBO (FGRSBO) was lower than the WFSBO group due to suppression of hepatic FAS expression. In the oil comparison study, TC and LDL-C concentrations in the FGRUSSO group were lower due to attenuated HMGCR activity. In conclusion, bugak prepared by traditional cooking methods was most effective for lowering plasma TG, TC, and LDL-C via suppressing hepatic FAS and HMGCR activity, although transcription factors for regulating lipogenic enzyme expression were not significantly different.

Reconstitution of anti-allergic activities of PG102 derived from Actinidia arguta by combining synthetic chemical compounds.

PG102, a water-soluble extract from an edible fruit, Actinidia arguta, has previously been shown to control various factors involved in allergy pathogenesis. It was investigated whether the original activities of PG102 could be reconstituted by mixing chemical compounds present in PG102. Six compounds present in PG102 were, individually or in the form of mixtures, tested for their effects on the expression of various Th2 cytokines and inflammatory mediators in the cell-based assay. Each chemical inhibited IL-4 expression to varying degrees. The chemical compounds were combined at a ratio present in PG102, resulting in two formulations, CQMIIH and CQM, consisting of all or the first three of the following chemicals, citric, quinic, and malic acids, myo-inositol, isoquercitrin, and 5-hydroxymethyl-2-furaldehyde. The mixtures reconstituted original activities of PG102 to a significant level. In the murine asthma model, CQM ameliorated asthmatic symptoms and significantly decreased the level of IgE and IL-5. The decreased phosphorylation of ERK1/2 was observed in cells and mice treated with PG102 and the mixtures. Our data indicated that the substantial portion of PG102's anti-allergic activities could be reconstituted, in vitro and in vivo, by mixing six chemical compounds, suggesting the possibility of developing a new type of anti-allergic agent. This approach may be useful for developing chemically defined functional products from complex botanical extracts.

Current statin usage for patients with acute coronary syndrome undergoing percutaneous coronary intervention: multicenter survey in Korea.

BACKGROUND: Although high-dose statin therapy has been reported to improve outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), patterns of statin usage for such patients have not been reported in real-world clinical practice. HYPOTHESIS: Some clinical factors would affect the pattern of statin usage in patients with ACS. METHODS: In the multicenter prospective registry, 3362 patients with ACS who underwent PCI were analyzed. High-dose statin treatment was defined as atorvastatin ≥40 mg or rosuvastatin ≥20 mg per day. The patterns of statin usage were investigated for 30 days after the index PCI. RESULTS: High-dose statins were administered prior to PCI to 13.7% and 19.6% of patients with unstable angina/non-ST-elevated myocardial infarction (UA/NSTEMI) and ST-elevated myocardial infarction (STEMI), respectively (P < 0.001). After PCI, 476 (14.2%) patients were maintained on high-dose statins, and 550 (16.4%) patients received no statins. Independent factors associated with high-dose statin usage after PCI were STEMI (odds ratio [OR]: 1.704, 95% confidence interval [CI]: 1.321-2.197, P < 0.001), high total cholesterol level (OR: 1.445, 95% CI: 1.136-1.837, P = 0.003), and current smoker (OR: 1.556, 95% CI: 1.206-2.008, P < 0.011). The absence of hypercholesterolemia was an independent factor determining the nonuse of statins (OR: 0.229, 95% CI: 0.148-0.353, P < 0.001). CONCLUSIONS: In real-world clinical practice, high-dose statin treatment is being underused despite extensive evidence for patients with ACS undergoing PCI, particularly in UA/NSTEMI. Efforts are needed to ensure that clinical practice complies with evidence-based guidelines.

Inhibitory effect of Poncirus trifoliate on acetylcholinesterase and attenuating activity against trimethyltin-induced learning and memory impairment.

Various native Korean plants were screened to find an effective acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer's disease (AD). Among these plants, the ethanol extract of Poncirus trifoliate was selected for isolating the AChE inhibitor because it exhibited the highest inhibitory activity (47.31%). To separate the active compound from Poncirus trifoliate, solvent partition, open column chromatography, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC) were utilized. The putative chemical structure of the AChE inhibitor was identified as methoxsalen by successive analysis with electron ionization mass spectrometry (EI-MS) and (13)C/(1)H-nuclear magnetic resonance (NMR). To confirm the attenuating effect of the Poncirus trifoliate extract against trimethyltin (TMT)-induced neurotoxicity, in vivo behavior tests were carried out. Our findings suggest that the Poncirus trifoliate extract significantly reversed TMT-induced learning and memory impairment. These results demonstrate that the Poncirus trifoliate extract could possess a wide range of beneficial activities for neurodegenerative disorders, notably AD.

Decursin and decursinol inhibit VEGF-induced angiogenesis by blocking the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase.

The root of Angelica gigas Nakai contains two major coumarins, which have been previously identified as decursin and decursinol. Decursin has been demonstrated to exhibit potent anti-cancer activity both in vitro and in vivo. In this study, we found that decursin and decursinol at non-cytotoxic doses inhibited the VEGF-induced proliferation, migration, and capillary-tube formation of HUVECs. Moreover, decursin and decursinol suppressed microvessel formation on chorioallantoic membranes in fertilized eggs and into mouse Matrigel plugs. The oral administration of decursin and decursinol also reduced VEGF-induced angiogenesis in Matrigel. Furthermore, decursin and decursinol reduced the phosphorylation of ERK and JNK, but not p38 MAPK, in VEGF-stimulated HUVECs. Taken together, our results reveal that decursin and decursinol inhibit VEGF-induced angiogenesis by reducing the activation of ERK and JNK in HUVECs, and possess potent in vivo anti-angiogenic activity, coupled with the advantage of oral dosing. Thus, these compounds may have the potential for the treatment of cancers dependent on VEGF-induced vascularization.

Bamboo culm extract supplementation elevates HDL-cholesterol and ameliorates oxidative stress in C57BL/6 mice fed atherogenic diet.

Previously, we reported that bamboo culms possess a stronger antioxidative capacity than bamboo leaves in vitro. In this study, we investigated whether bamboo culm extract (BCE) supplementation ameliorates oxidative stress and hepatic nuclear factor kappaB (NF kappa B) activation in C57BL/6 mice fed an atherogenic diet. In addition, the effect of BCE supplementation on plasma lipid levels of the animals was tested. The mice were randomly assigned to a normal diet, an atherogenic diet (control), or an atherogenic diet supplemented with 1% (wt/wt) BCE or 3% (wt/wt) BCE for 16 weeks. Atherogenic diet-induced oxidative stress, measured by hepatic thiobarbituric acid-reactive substances and protein carbonyls, was significantly lower in the BCE-supplemented groups than in the control (P < .05). Total antioxidative capacity was elevated in the BCE groups, along with greater activities of antioxidative enzymes such as superoxide dismutase and catalase, compared to the control or normal groups (P < .05). The hepatic NF kappa B binding activities were significantly lower in the BCE groups as well (P < .05). The high-density lipoprotein-cholesterol level was significantly elevated by BCE supplementation (P < .05), whereas the effects of BCE on triglyceride and total cholesterol were inconsistent. Results from this study suggest that BCE supplementation may lessen oxidative stress via a series of changes, including a reinforced antioxidant system, and also suggest that the lowered oxidative stress status may down-regulate the activation of inflammatory mediators.

Ameliorating effect of Gardenia jasminoides extract on amyloid beta peptide-induced neuronal cell deficit.

The brains of Alzheimer's disease (AD) patients are characterized by large deposits of amyloid beta peptide (Abeta). Abeta is known to increase free radical production in nerve cells, leading to cell death that is characterized by lipid peroxidation, free radical formation, protein oxi-dation, and DNA/RNA oxidation. In this study, we selected an extract of Gardenia jasminoides by screening, and investigated its ameliorating effects on Abeta-induced oxidative stress using PC12 cells. The effects of the extract were evaluated using the 2,7 -dichlorofluorescein diacetate (DCF-DA) assay and the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. To find the active component, the ethanol extract was partitioned with hexane, chloroform, and ethyl acetate, respectively, and the active component was purified by silica-gel column chromatography and HPLC. The results suggested that Gardenia jasminoides extract can reduce the cytotoxicity of Abeta in PC 12 cells, possibly by reducing oxidative stress.

Improvement of lipid profile by amaranth (Amaranthus esculantus) supplementation in streptozotocin-induced diabetic rats.

BACKGROUND/AIMS: Lipid disorders may exacerbate some complications of diabetes. Amaranth has been reported to exhibit a cholesterol-lowering effect in hyperlipidemic animals. The present study was designed to investigate the effect of amaranth on serum glucose and the lipid profile in diabetic rats. METHODS: Male Sprague-Dawley rats were assigned to normal control, diabetic control, diabetic amaranth-grain (AG)-supplemented (500 g/kg diet) and diabetic amaranth-oil (AO)-supplemented (90 g/kg diet) groups and fed experimental diets for 3 weeks. Effects were monitored on glucose tolerance, serum and liver lipids, and fecal excretions of lipids and bile acids. RESULTS: Fasting serum glucose levels and the glucose tolerance of diabetic rats were improved by AG and AO supplementation. Serum and liver lipids such as total cholesterol, triglyceride (TG) and very-low-density lipoprotein cholesterol concentrations were also lowered in diabetic animals by AG and AO consumption. Fecal excretions of cholesterol, TG and bile acid were markedly reduced in diabetic rats, and these parameters were dramatically increased by AG and AO supplementation. CONCLUSION: AG and AO supplementation improve the glucose and lipid metabolism in streptozotocin-induced diabetic rats.

Daidzein activates choline acetyltransferase from MC-IXC cells and improves drug-induced amnesia.

The choline acetyltransferase (ChAT) activator, which enhances cholinergic transmission via an augmentation of the enzymatic production of acetylcholine (ACh), is an important factor in the treatment of Alzheimer's disease (AD). Methanolic extracts from Pueraria thunbergiana exhibited an activation effect (46%) on ChAT in vitro. Via the sequential isolation of Pueraria thunbergiana, the active component was ultimately identified as daidzein (4',7-dihydroxy-isoflavone). In order to investigate the effects of daidzein from Pueraria thunbergiana on scopolamine-induced impairments of learning and memory, we conducted a series of in vivo tests. Administration of daidzein (4.5 mg/kg body weight) to mice was shown significantly to reverse scopolamine-induced amnesia, according to the results of a Y-maze test. Injections of scopolamine into mice resulted in impaired performance on Y-maze tests (a 37% decreases in alternation behavior). By way of contrast, mice treated with daidzein prior to the scopolamine injections were noticeably protected from this performance impairment (an approximately 12%-21% decrease in alternation behavior). These results indicate that daidzein might play a role in acetylcholine biosynthesis as a ChAT activator, and that it also ameliorates scopolamine-induced amnesia.

Deoxypodophyllotoxin, a naturally occurring lignan, inhibits the passive cutaneous anaphylaxis reaction.

This study examined the effect of a podophyllotoxin derivative, deoxypodophyllotoxin (anthricin), which is a medicinal herb product isolated from Anthriscus sylvestris Hoffm. Deoxypodophyllotoxin was tested in a rat PCA (passive cutaneous anaphylaxis) assay by administering deoxypodophyllotoxin intraperitoneally (1.0 to 10 mg/kg, i.p.) and intravenously (0.25 to 1.0 mg/kg, i.v.). Deoxypodophyllotoxin dose-dependently inhibited the PCA reaction activated by anti-dinitrophenyl (DNP) IgE. The PCA inhibitory activity of deoxypodophyllotoxin was stronger than those of prednisolone and indomethacin, which were used as positive controls. These results suggest that deoxypodophyllotoxin may be beneficial in regulating the immediate-type allergic reaction.

Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia.

This study was performed to identify safe and more effective acetylcholinesterase (AChE) inhibitors in the treatment of Alzheimer's disease. The total methanol extract of Citrus junos had a significant inhibitory effect on AChE in vitro. By sequential fractionation of C.junos, the active component was finally identified as naringenin. Naringenin inhibited AChE activity in a dose-dependent manner. In this study, we also evaluated the anti-amnesic activity of naringenin, a major flavanone constituent isolated from C. junos, in vivo using ICR mice with amnesia induced by scopolamine (1 mg/kg body weight). Naringenin, when administered to mice at 4.5 mg/kg body weight, significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance and the Y-maze test. These results suggest that naringenin may be a useful chemopreventive agent against Alzheimer's disease.

Effects of oleamide on choline acetyltransferase and cognitive activities.

We screened 50 Korean traditional natural plants to measure the activation effect on choline acetyltransferase and attenuation of scopolamine-induced amnesia. The methanolic extracts from Zizyphus jujuba among the tested 50 plants, showed the highest activatory effect (34.1%) on choline acetyltransferase in vitro. By sequential fractionation of Zizyphus jujuba, the active component was finally identified as cis-9-octadecenoamide (oleamide). After isolation, oleamide showed a 65% activation effect. Administration of oleamide (0.32%) to mice significantly reversed the scopolamine-induced memory and/or cognitive impairment in the passive avoidance test and Y-maze test. Injection of scopolamine to mice impaired performance on the passive avoidance test (31% decrease in step-through latency), and on the Y-maze test (16% decrease in alternation behavior). In contrast, mice treated with oleamide before scopolamine injection were protected from these changes (12-25% decrease in step-through latency; 1-10% decrease in alternation behavior). These results suggest that oleamide should be a useful chemo-preventive agent against Alzheimer's disease.

In vitro and in vivo antibacterial activities of DW286, a new fluoronaphthyridone antibiotic.

The in vitro and in vivo activities of DW286, a novel fluoronaphthyridone with potent antibacterial activity, were compared with those of ciprofloxacin, gemifloxacin, sparfloxacin, and trovafloxacin. Against gram-positive bacteria, such as Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis, the in vitro activity of DW286 was stronger than that of any other reference antibiotic. Against gram-negative bacteria, the activity of DW286 was similar to those of trovafloxacin and gemifloxacin but was weaker than that of ciprofloxacin. In a mouse systemic infection caused by three S. aureus strains, including methicillin-resistant S. aureus and quinolone-resistant S. aureus (QRSA), DW286 demonstrated the most potent activity, as found in vitro. Specially, DW286 is >or=8-fold more active against QRSA than the other fluoroquinolones. And the 50% protective doses for DW286 were correspondent with the in vitro activities.