Eun Ju Jeong

Cognitive-enhancing effects of Rhus verniciflua bark extract and its active flavonoids with neuroprotective and anti-inflammatory activities.

The neuroprotective potential of flavonoids within the brain comprises anti-apoptosis of neuronal cells, anti-neuroinflammation and enhancement of cognitive function. We reported that Rhus vernciflua inhibits glutamate-induced neurotoxicity in primary cultured rat cortical cells. Here we narrowed it down to get neuroprotective fractions from the plant yielding flavonoid-rich ethyl acetate fraction (PREF). Among its active flavonoids, fisetin exhibited not only inhibitory effect against lipopolysaccharide (LPS)-induced neuroinflammation by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also memory enhancing effects via reactivation of cAMP responsive element binding protein (CREB)-brain derived neurotrophic factor (BDNF) pathway in memory-impaired mice by scopolamine. Butein also showed a similar activity to fisetin even though to a lesser extent. The neuroprotection by PREF and selected flavonoids may involve maintenance of antioxidant defense mechanism including glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). Conclusively, we demonstrate the R. vernciflua bark extract and its active flavonoids with potent neuroprotective and anti-inflammatory effects might be good therapeutic candidates as cognitive-enhancers.

Cognition-enhancing and neuroprotective activities of the standardized extract of Betula platyphylla bark and its major diarylheptanoids.

Diarylheptanoids have been the center of the intensive research efforts for Alzheimers disease and other neurodegenerative diseases. The present study aimed to determine the effect of the standardized extract of B. platyphylla bark and its major diarylheptanoids in scopolamine-induced amnesic mice through cyclic AMP response element-binding protein (CREB) activation. Oral administration of the standardized extract of B. platyphylla bark (100mg/kg body weight), aceroside VIII (1mg/kg body weight) and platyphylloside (1 or 2mg/kg body weight) significantly ameliorated scopolamine-induced amnesia in passive avoidance test. CREB phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the cortex and hippocampus of the scopolamine-treated mice were markedly increased by the treatment of the standardized extract of B. platyphylla bark and platyphylloside. The standardized extract of B. platyphylla bark and its major diarylheptanoids also significantly protected HT22 cells against neurotoxicity induced by glutamate insult. The standardized extract of B. platyphylla bark and platyphylloside may ameliorate memory deficits by activating the CREB-BDNF pathway and prevent a neurodegeneration by inhibiting neuronal cell death.

Neuroprotective biflavonoids of Chamaecyparis obtusa leaves against glutamate-induced oxidative stress in HT22 hippocampal cells

Four biflavonoids (1-4), five flavonoids glycosides (5-9), two catechins (10, 11), two lignans (12-13), neolignan glycoside (14) and phenylpropanoid glycoside (15) were isolated from the leaves of Chamaecyparis obtusa (Cupressaceae). Neuroprotective effects of the isolated compounds were evaluated employing HT22 mouse hippocampal cells, a model system to study glutamate-induced oxidative stress. The glutamate injured HT22 cells were protected significantly by amentoflavone (3), ginkgetin (4) and (-)-epitaxifolin 3-O-β-D-xylopyranoside (9). The reduced activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione reductase (GR) in response to high concentration of glutamate were preserved by pre-treatment of 3, 4 or 9, while the activities of glutathione peroxidase (Gpx) and catalase (CAT) were little affected. The reduced content of GSH induced by glutamate was also recovered by 3, 4 or 9 in accommodation with the decrease in ROS production. In addition, the phosphorylation of ERK1/2 induced by glutamate insult was clearly prevented by 3, while little changed by 4. Taken together, amentoflavone (3), ginkgetin (4) and (-)-epitaxifolin 3-O-β-D-xylopyranoside (9) derived from C. obtusa could protect HT22 neuronal cells against glutamate-induced oxidative damage through preserving antioxidant enzymes activities and/or inhibiting ERK1/2 activation.

Antiproliferative triterpenes from the leaves and twigs of Juglans sinensis on HSC-T6 cells.

Bioassay-guided fractionation of an 80% MeOH extract of leaves and twigs of Juglan sinensis has resulted in the isolation of four new triterpenes (1-4) and 17 known triterpenes (5-21). The new compounds were determined to be 1-oxo-3β,23-dihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside (1), 1-oxo-3β-hydroxyolean-18-ene (2), 3β,23-dihydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranoside (3), and 3β,22α-dihydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranoside (4) by spectroscopic analysis. Compounds 2, 13, 15, and 21 showed antiproliferative activities (14.2, 14.8, 15.6, and 11.0% at 100 μM, respectively) in HSC-T6 cells. Flow cytometry assays revealed that these compounds inhibited HSC-T6 proliferation by inducing apoptosis.

Salicortin-Derivatives from Salix pseudo-lasiogyne Twigs Inhibit Adipogenesis in 3T3-L1 Cells via Modulation of C/EBPα and SREBP1c Dependent Pathway

Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2′,6′-O-acetylsalicortin (1), 2′-O-acetylsalicortin (2), 3′-O-acetylsalicortin (3), 6′-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2′,6′-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC50 value of 11.6 μM, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2′,6′-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBPβ during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2′,6′-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBPα and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity.

Densanins A and B, New Macrocyclic Pyrrole Alkaloids Isolated from the Marine Sponge Haliclona densaspicula

Densanins A (1) and B (2) were isolated from the sponge Haliclona densaspicula. On the basis of spectral data and the Mosher ester method, the complete structures were characterized as hexacyclic diamine alkaloids, which were probably derived from 3-alkylpyridine. Compounds 1 and 2 showed relatively potent inhibitory effects on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells with IC(50) values of 1.05 and 2.14 μM, respectively.

Characterization and anti-inflammatory effects of iodinated acetylenic acids isolated from the marine sponges Suberites mammilaris and Suberites japonicus.

The previously unknown compounds 1-4, acetylenic acids with one or two iodine atom(s), were isolated from the marine sponges Suberites mammilaris and Suberites japonicus. Their complete structures were determined using NMR and mass spectrometry. The methylated compounds 1a and 2a exhibited a strong NO inhibitory effect on RAW264.7 cells, while methylated 3a and 4a were inactive in RAW264.7 cells, but highly active in BV2 microglia cells.

Hepatoprotective effects of Limonium tetragonum, edible medicinal halophyte growing near seashores

Background: During the process of hepatic fibrosis, the activation of hepatic stellate cells (HSCs) is responsible for the increased formation and reduced degradation of extracellular matrix in the liver. By employing the hepatic stellate cell line, HSC-T6, it was found that the methanol extract of Limonium tetragonum, a halophyte living in salt marsh near south and western seashores of Korea significantly inhibited the proliferation of HSC-T6 cells. Objective: In the present study, we attempted to investigate the antifibrotic effects of the mathanolic extract of L. tetragonum (MELT) in the activated HSC-T6 cells. Materials and Methods: The proliferation of HSC-T6 was stimulated by culturing environment or platelet-derived growth factor (PDGF-BB) insult, and then the inhibitory activities of MELT were measured. Results: It was found that MELT suppressed the proliferation of the activated HSC-T6 in concentration- and time-dependent manners. The increased collagen deposition in the activated HSC-T6 cells was also decreased by the treatment of MELT. The maximal dose of MELT, however, had little effect on primary cultured rat hepatocytes. Wlammatory cytokine, tumor necrosis factor alpha (TNF-α) produced by lipopolysaccharide-stimulated RAW264.7 macrophages was inhibited by MELT. Conclusion: Collectively, the above results demonstrated that MELT suppressed HSCs proliferation but not in hepatocytes, implying that L. tetragonum may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.

Anti-obesity Effect of Dioscorea oppositifolia Extract in High-Fat Diet-Induced Obese Mice and Its Chemical Characterization

Dioscorea oppositifolia is a well-known edible and traditional medicine for the treatment of gastrointestinal diseases. In our previous study, D. oppositifolia exhibited both pancreatic lipase inhibition and an anti-adipogenesis effect in vitro. This study was performed to investigate the anti-obesity effect of D. oppositifolia on high-fat diet-induced obese mice. Female ICR mice were fed a high-fat diet with the 100 mg/kg of D. oppositifolia n-BuOH extract for 8 weeks. The high-fat diet mice received the 15 mg/kg Orlistat orally as a positive control. The body weight, parametrial adipose tissue weight, and the levels of triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL)-cholesterol in blood serum of female ICR mice were significantly decreased by feeding a high-fat diet with the n-BuOH extract of D. oppositifolia. An inhibitory effect of D. oppositifolia extract on dietary fat absorption was also clearly shown. The D. oppositifolia sample was found to contain 3,5-dimethoxy-2,7-phenanthrenediol and (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)-3,5-heptanediol as main components based on its phytochemical analysis. The present study is the first report of the anti-obesity effect by D. oppositifolia n-BuOH extract using an established disease model. The increase in fecal fat excretion by treatment of D. oppositifolia may be an effective approach for treating obesity and related diseases.

Protective Effects of Ethyl Acetate Soluble Fraction of Limonium tetragonum on Diethylnitrosamine-Induced Liver Fibrosis in Rats

Diethylnitrosamine (DEN) is a potent toxic material that can cause necrosis and subsequent fibrosis in the liver. Based on the previously reported hepatoprotective effect of Limonium tetragonum against the proliferation of hepatic stellate cells, we tested the EtOAc soluble fraction of L. tetragonum extract (EALT) in a DEN-induced hepatotoxic rat model. The development of hepatotoxicity including mononuclear cell infiltration and fibrosis induced by intraperitoneal injections of DEN (70 mg/2 mL/kg body weight (b.w.) per week) was observed at 4, 6 and 8 weeks after the first DEN treatment. Administration of EALT (200 mg/kg body weight, per os (p.o.)) induced significant reductions in serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and triglycerides (TG) in DEN-injected rats. Increased oxidative stress in DEN-induced liver fibrosis rats was diminished by EALT treatment through a decrease in malondialdehyde (MDA) and increase in superoxide dismutase (SOD). Histologic findings that included markedly attenuated mononuclear cell infiltration and fibrosis could be observed in liver samples from the EALT-treated groups. An extract of Hovenia dulcis fruit and Sylimarin were used as positive controls. The present study provides direct experimental evidence for EALT attenuated hepatic injury and fibrosis in DEN-treated mice. The L. tetragonum EtOAc fraction might be useful in treating fibrotic liver diseases.