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Find video protocols related to scientific articles indexed in Pubmed.
Antioxidant defense and hepatoprotection by procyanidins from almond (Prunus amygdalus) skins.
J. Agric. Food Chem.
PUBLISHED: 08-13-2014
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Procyanidins, polymeric flavan-3-ols, are known to possess antioxidant, antiatherogenic, and anticarcinogenic properties. In the present study, we investigated the role of almond (Prunus amygdalus) skin procyanidins (ASP) in regulating the protein expression of phase II detoxifying and antioxidant enzymes in HepG2 cells and acetaminophen (APAP)-treated hepatotoxic mice. Treatments of ASP significantly induced the expression of phase II enzymes including
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Korean propolis suppresses angiogenesis through inhibition of tube formation and endothelial cell proliferation.
Nat Prod Commun
PUBLISHED: 05-30-2014
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Propolis, a sticky material that honeybees collect from living plants, has been used for its pharmaceutical properties since ancient times. In this study, we examined the effects of ethanol extracts of Korean propolis (EEKP) from various geographic regions on the inhibition of angiogenesis, both in vitro and in vivo. The effects of EEKP were tested on in vitro models of angiogenesis, that is, tube formation and proliferation of human umbilical vein endothelial cells (HUVECs). All EEKP samples exhibited significant inhibitory effects on tube formation of HUVECs in a concentration-dependent manner (6.25-25 microg/mL). In addition, two EEKP samples, prepared from Uijeongbu and Pyoseon propolis, significantly suppressed the proliferation of HUVECs in a concentration-dependent manner (3.13-25 microg/mL). Furthermore, in an in vivo angiogenesis assay using the chick embryo chorioallantoic membrane (CAM) system, we found that the two EEKP samples significantly reduced the number of newly formed vessels. These results indicate that Korean propolis may have potential applications in the prevention and treatment of angiogenesis-related diseases such as cancer.
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p-Coumaric acid and ursolic acid from Corni fructus attenuated ?-amyloid(25-35)-induced toxicity through regulation of the NF-?B signaling pathway in PC12 cells.
J. Agric. Food Chem.
PUBLISHED: 05-19-2014
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Neuroinflammatory responses induced by amyloid-beta peptide (A?) are important causes in the pathogenesis of Alzheimer's disease (AD). Blockade of A? has emerged as a possible therapeutic approach to control the onset of AD. This study investigated the neuroprotective effects and molecular mechanisms of p-coumaric acid (p-CA) and ursolic acid (UA) from Corni fructus against A?(25-35)-induced toxicity in PC12 cells. p-CA and UA significantly inhibited the expression of iNOS and COX-2 in A?(25-35)-injured PC12 cells. Blockade of nuclear translocation of the p65 subunit of nuclear factor ?B (NF-?B) and phosphorylation of I?B-? was also observed after p-CA and UA treatment. For the upstream kinases, UA exclusively reduced ERK1/2, p-38, and JNK phosphorylation, but p-CA suppressed ERK1/2 and JNK phosphorylation. Both compounds comprehensively inhibited NF-?B activity, but possibly with different upstream pathways. The results provide new insight into the pharmacological modes of p-CA and UA and their potential therapeutic application to AD.
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Kaempferol attenuates the glutamate-induced oxidative stress in mouse-derived hippocampal neuronal HT22 cells.
Food Funct
PUBLISHED: 04-29-2014
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It is thought that the neuronal cell loss caused by oxidative stress is the primary mechanism underlying the pathogenesis of several neurodegenerative disorders. Glutamate is an endogenous neurotransmitter, but at high concentrations it can act as a neurotoxicant by increasing the intracellular levels of reactive oxygen species (ROS). Therefore, the development of factors that can attenuate glutamate-induced oxidative stress in neuronal cells is a good strategy by which new drugs could be discovered that may treat or prevent neurodegenerative diseases. Here, the neuroprotective effects of kaempferol (KF) isolated from the stems of butterbur (Petasites japonicus) were examined in glutamate-treated hippocampal neuronal cells (HT22). The administration of KF (25 ?M) resulted in a significant increase in cell viability (105.18 ± 7.48%) compared with the control (100.00 ± 3.05%), while glutamate (5 mM) reduced cell viability by 39.94 ± 1.61%. The glutamate-induced calcium (Ca(2+)) influx (1.93 ± 0.08-fold) was significantly reduced by 0.89 ± 0.02-fold following the administration of 25 ?M KF. Additionally, when HT22 cells were stressed with excessive glutamate, there was a 3.70 ± 0.01-fold increase in intracellular ROS generation, even though this was effectively attenuated by KF (25 ?M, 0.72 ± 0.01-fold). The protective effects of KF in HT22 cells were later confirmed using a lactate dehydrogenase (LDH) assay and a FITC-annexin V/propidium iodide double staining procedure. These findings also revealed that the neuroprotective effects of KF are a result of the regulation of the expression levels of proteins, such as Bcl-2, Bid, apoptosis-inducing factor (AIF), and mitogen-activated protein kinase (MAPK). This is the first report to investigate the neuroprotective influence of KF in glutamate-treated HT22 cells. These data demonstrate that KF may be a useful candidate for pharmacological therapies that can prevent and treat neurodegenerative diseases such as Alzheimer's disease (AD).
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Safety of red ginseng oil for single oral administration in Sprague-Dawley rats.
J Ginseng Res
PUBLISHED: 02-22-2014
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The single oral administration of red ginseng oil (5000 mg/kg) to Sprague-Dawley rats induced no changes in behavioral patterns, clinical signs, and body weight, and hepatotoxicity parameters such as aspartate aminotransferase and alanine aminotransferase for 14 d. Therefore, these results suggest that the red ginseng oil is safe and nontoxic acutely.
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Oleic acid and linoleic acid from Tenebrio molitor larvae inhibit BACE1 activity in vitro: molecular docking studies.
J Med Food
PUBLISHED: 02-20-2014
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In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC??) value of 61.31 ?M and Ki value of 34.3??M. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH? of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors.
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In vitro BACE1 inhibitory activity of geraniin and corilagin from Geranium thunbergii.
Planta Med.
PUBLISHED: 07-22-2013
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Generation of amyloid ? peptide through the proteolytic process of amyloid precursor protein by ?-secretase and ?-secretase is a main casual factor of Alzheimers disease, since amyloid ? peptide is a major and crucial component of senile plaques in Alzheimers disease brains. In the process of searching for ?-secretase inhibitors from natural resources, the EtOAc soluble fraction of Geranium thunbergii exhibited significant ?-secretase inhibitory activity. Two compounds, geraniin and corilagin, isolated from the most active EtOAc fraction of G. thunbergii, exhibited predominant inhibition against ?-secretase with IC?? values of 4.0 × 10?? M and 3.4 × 10?? M, respectively. Dixon plot of geraniin and corilagin demonstrated that the ?-secretase inhibition was noncompetitive with the substrate, thus clearly suggesting that these compounds might bind either to the ?-secretase subsites or to another regulatory domain with Ki values of 2.8 × 10?? M and 7.9 × 10?? M, respectively. Both compounds exhibited no significant inhibition against ?-secretase and other serine proteases including trypsin and chymotrypsin, showing that they were relatively specific and selective inhibitors of ?-secretase. These novel findings suggest that geraniin and corilagin from G. thunbergii may be effective therapeutic agents for further drug development in Alzheimers disease.
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Anti-inflammatory effect of procyanidins from wild grape (Vitis amurensis) seeds in LPS-induced RAW 264.7 cells.
Oxid Med Cell Longev
PUBLISHED: 06-23-2013
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In the present study, the anti-inflammatory effect and underlying mechanisms of wild grape seeds procyanidins (WGP) were examined using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells. We used nitric oxide (NO) and prostaglandin E2 (PGE2) and reactive oxygen species (ROS) assays to examine inhibitory effect of WGP and further investigated the mechanisms of WGP suppressed LPS-mediated genes and upstream expression by Western blot and confocal microscopy analysis. Our data indicate that WGP significantly reduced NO, PGE2, and ROS production and also inhibited the expression of proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions. Consistently, WGP significantly reduced LPS-stimulated expression of proinflammatory cytokines such as tumor necrosis factor ? (TNF-?) and interleukin- (IL-) 1 ? . Moreover, WGP prevented nuclear translocation of nuclear factor- ? B (NF ? B) p65 subunit by reducing inhibitory ? B- ? (I ? B ?) and NF ? B phosphorylation. Furthermore, we found that WGP inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). Taken together, our results demonstrated that WGP exerts potent anti-inflammatory activity through the inhibition of iNOS and COX-2 by regulating NF ? B and p38 MAPK pathway.
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Stimulation of activity and expression of antioxidant enzymes by solvent fractions and isolated compound from Cedrela sinensis leaves in HepG2 cells.
J Med Food
PUBLISHED: 02-08-2011
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Cedrela sinensis has been widely used in traditional Oriental medicine to treat a variety of diseases. However, little is known about the cellular actions by which this plant mediates its antioxidant effects. In this study, activity-guided fractionations of C. sinensis leaves were performed using column chromatographic techniques as well as biological assays with HepG2 cells. The ethanol (95%) extract of C. sinensis leaves was sequentially extracted with hexane, chloroform, ethyl acetate (EtOAc), butanol, and water, and the fractions were screened for their antioxidant potentials for scavenging radicals as well as inducing antioxidant enzyme activity and expression. The most potent antioxidant EtOAc fraction was further separated using chromatographic techniques including open column and high-performance liquid chromatography. Compound 1 from the EtOAc fraction showed strong radical scavenging activity with a 50% scavenging concentration value close to that of ascorbic acid and induced both the activity and expressions of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Inhibitory effects on the phosphorylations of upstream mitogen-activated protein kinases such as c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38 were also observed after treatments with compound 1. Compound 1 was identified as quercitrin by (1)H- and (13)C-nuclear magnetic resonance techniques. Taken together, our findings demonstrated for the first time that C. sinensis leaves appear to be a useful source of a cytoprotective and chemopreventive agent that can stimulate the activity and expression of crucial antioxidant enzymes in cells.
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Fatty Acid and Volatile Oil Compositions of Allomyrina dichotoma Larvae.
Prev Nutr Food Sci
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Thirty-two different volatile oils were identified from Allomyrina dichotoma (A. dichotoma) larvae by gas chromatography/mass spectrometry (GC/MS). The major volatile components were 2,2,4-trimethyl-3-carboxyisopropyl pentanoic acid isobutyl ester (5.83%), phenol,2,6-bis(a,a-dimethyl ethyl)-4-(1-methyl-1-phenylethyl) (5.72%), heptacosane (5.49%) and phenol,2,4-bis(1-methyl-1-phenylethyl) (5.47%). The composition of the fatty acids in A. dichotoma larvae was also determined by gas chromatography (GC) and fourteen constituents were identified. Oleic acid (19.13%) was the most abundant fatty acid followed by palmitic acid (12.52%), palmitoleic acid (3.71%) and linoleic acid (2.08%) in 100 g of A. dichotoma larvae on a dry weight basis. The quantity of unsaturated fatty acids (64.00%) were higher than that of saturated ones (36.00%). The predominant fatty acids in A. dichotoma consist of monounsaturated fatty acid (MUFA, 57.70%) such as oleic acid, myristoleic acid and palmitoleic acid, followed by saturated fatty acids (36.00%) and polyunsaturated fatty acids (PUFA, 6.50%). In particular, the presence of essential fatty acids, such as linoleic (5.30%) and linolenic acid (0.40%) give A. dichotoma larvae considerable nutritional and functional value and it may be a useful source for food and/or industrial utilization.
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Protective effects of the key compounds isolated from Corni fructus against ?-amyloid-induced neurotoxicity in PC12 cells.
Molecules
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?-Amyloid (A?) peptide is the major component of senile plaques and is considered to have a causal role in the development and progression of Alzheimer’s disease (AD). There is compelling evidence supporting the notion that A?-induced cytotoxicity is mediated though the generation of ROS. In the present study, we investigated the neuroprotective effects of ursolic acid (UA), p-coumaric acid (p-CA), and gallic acid (GA) isolated from Corni fructus (CF) against A?(25-35)-induced toxicity in PC12 cell. Exposure of PC12 cells to 50 ?M A?(25-35) increased cellular oxidative stress, the number of apoptotic cells and caspase-3 activity and finally caused significant cell death. However, UA, p-CA, and GA not only suppressed the generation of ROS but also attenuated DNA fragmentation and eventually attenuated A?-induced apoptosis in a dose-dependent manner. In protecting cells against A? neurotoxicity, UA and GA possessed stronger ability against ROS generation than p-CA, while p-CA showed the strongest anti-apoptotic activity. Particularly, p-CA protected cells at the concentration range from 0.5 up to 125 ?M without any adverse effect. Taken together, these effects of UA, p-CA, and GA may be partly associated with the neuroprotective effect of CF. Furthermore, our findings might raise a possibility of therapeutic applications of CF for preventing and/or treating neurodegenerative diseases.
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?-Secretase (BACE1) inhibitory property of loganin isolated from Corni fructus.
Nat. Prod. Res.
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In the course of searching for anti-dementia agents from natural products, loganin isolated from EtOAc fraction of Corni fructus possessed specific inhibitory activity against ?-secretase (BACE1) with 9.2?×?10?? ?M and K(i) value of 5.5?×?10?? M. Loganin exhibited less inhibitory activity to ?-secretase (TACE) and other serine proteases exhibiting that it was a relatively specific inhibitor of BACE1. These novel findings suggest that loganin may be used to attenuate the progression and/or prevention of Alzheimers disease.
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6-shogaol-rich extract from ginger up-regulates the antioxidant defense systems in cells and mice.
Molecules
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The rhizome of ginger (Zingiber officinale Roscoe) is known to have several bioactive compounds including gingerols and shogaols which possess beneficial health properties such as anti-inflammatory and chemopreventive effects. Based on recent observations that 6-shogaol may have more potent bioactivity than 6-gingerol, we obtained a 6-shogaol-rich extract from ginger and examined its effects on the nuclear factor E2-related factor2 (Nrf2)/antioxidant response element (ARE) pathway in vitro and in vivo. 6-Shogaol-rich extract was produced by extracting ginger powder with 95% ethanol at 80 °C after drying at 80 °C (GEE8080). GEE8080 contained over 6-fold more 6-shogaol compared to the room temperature extract (GEE80RT). In HepG2 cells, GEE8080 displayed much stronger inductions of ARE-reporter gene activity and Nrf2 expression than GEE80RT. GEE8080 stimulated phosphorylations of mitogen-activated protein kinases (MAPKs) such as ERK, JNK, and p38. Moreover, the GEE8080-induced expressions of Nrf2 and HO-1 were attenuated by treatments of SB202190 (a p38 specific inhibitor) and LY294002 (an Akt specific inhibitor). In a mouse model, the GEE8080 decreased the diethylnitrosamine (DEN)-mediated elevations of serum aspartate transaminase and alanine transaminase as well as the DEN-induced hepatic lipid peroxidation. Inductions of Nrf2 and HO-1 by GEE8080 were also confirmed in the mice. In addition, the administration of GEE8080 to the mice also restored the DEN-reduced activity and protein expression of hepatic antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. In conclusion, GEE8080, a 6-shogaol-rich ginger extract, may enhance antioxidant defense mechanism through the induction of Nrf2 and HO-1 regulated by p38 MAPK and PI3k/Akt pathway in vitro and in vivo.
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Antioxidant and Hepatoprotective Effects of the Red Ginseng Essential Oil in H(2)O(2)-Treated HepG2 Cells and CCl(4)-Treated Mice.
Int J Mol Sci
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The aim of this study was to evaluate the antioxidant mechanisms of red ginseng essential oil (REO) in cells as well as in an animal model. REO was prepared by a supercritical CO(2) extraction of waste-products generated after hot water extraction of red ginseng. In HepG2 cells, REO diminished the H(2)O(2)-mediated oxidative stress and also restored both the activity and expression of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Administration of REO inhibited the phosphorylation of upstream mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38. In mice, the CCl(4)-mediated elevation of serum aspartate transaminase and alanine transaminase as well as the induction of hepatic lipid peroxidation were decreased by REO administration. REO treatments also resulted in up-regulation of the antioxidant enzyme expression in the liver. Moreover, increased phosphorylations of MAPKs were inhibited after REO administration. Overall, REO seems to protect the liver from oxidative stress through the activation and induction of antioxidant enzymes via inhibition of MAPKs pathways.
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Inhibitory effects of key compounds isolated from Corni fructus on BACE1 Activity.
Phytother Res
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Progressive cerebral deposition of A? in the brain is a seminal event in the pathogenesis of Alzheimers disease (AD). A? is generated from the amyloid precursor protein (APP) by proteolytic processing of ?-secretase (BACE1) and ?-secretase. Consequently, BACE1, a key enzyme in the production of A?, is a prime target for therapeutic intervention in AD. In the course of screening for natural BACE1 inhibitors from Corni fructus, the ethyl acetate (EtOAc) fraction showed significant inhibitory activity against BACE1. By activity guided purification, three compounds of BACE1 inhibitors p-coumaric acid, gallic acid and ursolic acid were isolated from Corni fructus EtOAc fraction. All isolated compounds suppressed BACE1 in a dose dependent manner. p-Coumaric acid, in particular, exhibited significant inhibitory activity against BACE1 with 9.0?×?10(-5) ?m and a K(i) value of 1.9?×?10(-6) ?m. Also this compound was non-competitive with a substrate in the Dixon plot, suggesting that it might bind either to the ?-secretase subsite or to another regulatory site. All compounds showed no significant attenuation of TACE (?-secretase) and other serine proteases such as chymotrypsin and trypsin, demonstrating that they were relatively selective and specific inhibitors of BACE1. These novel findings suggest that Corni fructus contains biologically active components that may be used to attenuate the progression and/or prevention of Alzheimers disease.
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Procyanidins from Wild Grape (Vitis amurensis) Seeds Regulate ARE-Mediated Enzyme Expression via Nrf2 Coupled with p38 and PI3K/Akt Pathway in HepG2 Cells.
Int J Mol Sci
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Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1-F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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