Fermented Castanea crenata Inner Shell Extract Increases Fat Metabolism and Decreases Obesity in High-Fat Diet-Induced Obese Mice.

The anti-obesity effects of fermented Castanea crenata inner shell extract (FCCE) were investigated using high-fat diet (HFD)-induced obese mice. In the FCCE intake groups, body weight gain and adipocyte area were significantly reduced, especially body weight gain in the 250 mg/kg FCCE group (G4) decreased by 37%, respectively, compared with negative control group (G2, HFD group). After oral administration of the FCCE, the increase of serum low-density lipoprotein (LDL)-cholesterol induced by HFD was suppressed significantly, as well as the level of aspartate aminotransferase, and alanine aminotransferase, which are markers of hepatitis induced by obesity. Serum leptin in G4 group was significantly decreased to less than that of G2 group. Also, in G4 and 500 mg/kg FCCE group (G5), enzymes-related lipogenesis, citrate synthase, and ATP citrate lyase were decreased, whereas the level of enoyl-CoA hydratase used for ß-oxidation was significantly increased in comparison with normal diet group. Furthermore, the FCCE stimulated the expression of lipolytic regulators, especially AMP-activated protein kinase. In conclusion, we suggest that the FCCE may ameliorate in diet-induced obesity by regulating lipid metabolism.

Antiobesity Effect of Garlic Extract Fermented by Lactobacillus plantarum BL2 in Diet-Induced Obese Mice.

Obesity is viewed as a serious public health problem. This study aimed to investigate the antiobesity effects of fermented garlic extract by lactic acid bacteria (LAFGE) on obesity. Male C57BL/6J mice were fed with high-fat diet (HFD) to induce obesity. The HFD-induced obese mice were orally administrated with 250 or 500 mg/kg LAFGE for 8 weeks. Feeding HFD-fed mice with 250 or 500 mg/kg LAFGE reduced body weight by 14% and 18%, respectively, compared to HFD. HFD-fed mice with 500 mg/kg LAFGE administration had lower epididymal, retroperitoneal, and mesenteric adipose tissue mass by 36%, 44%, and 63%, respectively, compared to HFD. The concentration of plasma triacylglyceride and total cholesterol was significantly lower in the HFD-fed mice with LAFGE administration. Moreover, LAFGE supplementation suppressed adipogenesis by downregulation in mRNA and protein expression of PPARγ, C/EBPα, and lipogenic proteins, including SREBP-1c, FAS, and SCD-1. Based on these findings, LAFGE may ameliorate diet-induced obesity by inhibiting adipose tissue hypertrophy by suppressing adipogenesis.

Germinated Waxy Black Rice Suppresses Weight Gain in High-Fat Diet-Induced Obese Mice.

This study was performed to investigate the antiobesity effect of germinated waxy black rice (GWBR) in high-fat diet (HFD)-induced obese mice. The mice were divided into a normal diet (ND) group, HFD group, and 2 test groups for 8 weeks: 2.5% GWBR-supplemented (GWBR-2.5) group and 5% GWBR-supplemented (GWBR-5) group. Supplementing with GWBR significantly reduced body weight gain and lipid accumulation in the liver and adipose tissue compared to the HFD control group. Triglyceride (TG), total cholesterol, and low-density lipoprotein-cholesterol levels in serum were decreased by GWBR supplementation, whereas high-density lipoprotein-cholesterol level significantly increased. In addition, mRNA levels of transcriptional factors, such as peroxisome proliferator-activated receptor-γ, CCAAT enhancer-binding protein (C/EBP)-α, C/EBP-ß, sterol regulatory element-binding protein-1c, and related genes, including adipocyte fatty acid-binding protein, fatty acid synthase, and lipoprotein lipase, were significantly lower in the GWBR groups. However, lipolytic enzymes, such as hormone-sensitive lipase, adipose TG lipase, and carnitine palmitoyltransferase-1, and uncoupling protein 2 mRNA levels were significantly higher in GWBR-supplemented mice. These results suggest that GWBR exerts antiobesity effects by decreasing lipid accumulation and promoting lipolysis in HFD-induced obese mice.

Germinated brown rice extract inhibits adipogenesis through the down-regulation of adipogenic genes in 3T3-L1 adipocytes.

The aim of this study was to examine the anti-adipogenic effect of germinated brown rice methanol extract (GBR) in 3T3-L1 adipocytes. The GBR inhibited adipocyte differentiation was measured by Oil Red O staining and glycerol-3-phosphate dehydrogenase (GPDH) activity in a dose-dependent manner without initiating any cytotoxicity. The mRNA levels of adipogenic transcription factors such as CCAAT/enhancer binding protein (C/EBPα), proliferator-activated receptorγ (PPARγ), and sterol regulatory element-binding protein-1c (SREBP-1c), and adipogenic genes, such as fatty acid synthase (FAS), adipocyte fatty acid-binding protein (aP2), and lipoprotein lipase (LPL), were significantly down-regulated by treatment with GBR when compared to that of untreated control cells. Moreover, tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) mRNA expressions were attenuated by GBR in mature adipocytes. These data suggest that GBR exhibits an anti-adipogenic effect through the suppression of adipogenesis in 3T3-L1 adipocytes.

Anti-obesity effects of germinated brown rice extract through down-regulation of lipogenic genes in high fat diet-induced obese mice.

Lipid accumulation using Oil Red O dye was measured in 3T3-L1 murine adipocytes to examine the anti-obesity effect of four types of germinated rice, including germinated brown rice (GBR), germinated waxy brown rice (GWBR), germinated black rice (GB-R), and germinated waxy black rice (GWB-R). GBR methanol extract exhibited the highest suppression of lipid accumulation in the 3T3-L1 cell line and also the anti-obesity effect of GBR on high fat induced-obese mice. The mice were divided into three groups and were administered: ND, a normal diet; HFD control, a high fat diet; and GBR, a high fat diet plus 0.15% GBR methanol extract for 7 weeks. GBR administration significantly decreased body weight gain and lipid accumulation in the liver and epididymal adipose tissue as compared to the HFD control group. In addition, serum triglycerides (TGs) and total cholesterol (TC) levels were significantly decreased by following GBR administration compared with those in the HFD control group, whereas the high-density lipoprotein (HDL) cholesterol level increased. Furthermore, the mRNA levels of adipogenic transcriptional factors, such as CCAAT enhancer binding protein (C/EBP)-α, sterol regulatory element-binding protein (SREBP)-1c, and peroxisome proliferator activated receptors (PPAR)-γ, and related genes (aP2, FAS), decreased significantly. Taken together, GBR administration suppressed body weight gain and lipid accumulation in the liver and epididymal adipocytes, and improved serum lipid profiles, in part, by controlling adipogenesis through a reduction in transcriptional factors. These results suggest that GBR is a potential agent against obesity.

Effects of methoxsalen from Poncirus trifoliata on acetylcholinesterase and trimethyltin-induced learning and memory impairment.

Previously, we identified methoxsalen (8-methoxy-2',3',6,7-furocoumarin) as the bioactive compound probably responsible for acetylcholinesterase (AchE) inhibition achieved by feeding crude extract of Poncirus trifoliate. To confirm the activity of methoxsalen, Institute of Cancer Research (ICR) mice were fed a control or a methoxsalen-supplemented diet for 4 weeks, and then learning and memory enhancing effects with respect to trimethyltin (TMT)-induced neurotoxicity were evaluated. The brain tissues of ICR mice were dissected after completion of the behavioral tests for biochemical analysis. Methoxsalen effectively reversed TMT-induced memory impairment on both Y-maze and passive avoidance tests. Brain AchE activity was inhibited by the oral consumption of all concentrations of methoxsalen. Moreover, the level of oxidative stress was significantly ameliorated in the groups on methodsalen containing diets. This is the first in vivo study conducted with methoxsalen in the field of AD research, and it indicates that further investigation of methoxsalen is warranted.

Inhibitory effect of pomegranate on intestinal sodium dependent glucose uptake.

Intestinal glucose uptake is mainly performed by its specific transporters, SGLT1 and GLUTs expressed in the intestinal epithelial cells. By using Caco-2 cells and 2-NBDG, we observed that intestinal glucose uptake was markedly inhibited by pomegranate (Punica granatum L, PG) among 200 screened edible Korean plants. The effects of the PG extract on Na(+)-dependent glucose uptake were further evaluated using brush border membrane vesicles (BBMV) obtained from the mouse small intestine. PG inhibited Na(+)-dependent glucose uptake with the IC(50) value of 424 µg/ml. The SGLT1 protein expression was dose dependently down regulated with PG treatment in Caco-2 cells. We next assessed the antihyperglycemic effect of PG in streptozotocin (STZ)-induced diabetic mice. Administration of PG (800 mg/kg) to STZ mice for four weeks improved postprandial glucose regulation. Furthermore, elevated Na(+)-dependent glucose uptake by BBMV isolated from STZ mice was normalized by PG treratment. These results suggest that PG could play a role in controlling the dietary glucose absorption at the intestinal tract by decreasing SGLT1 expression, and may contribute to blood glucose homeostasis in the diabetic condition.

Punica granatum protects against oxidative stress in PC12 cells and oxidative stress-induced Alzheimer's symptoms in mice.

Alzheimer's disease (AD) is a progressive degenerative brain disorder that is characterized by neuronal loss, neurofibrillary tangles, and the abnormal deposition of senile plaque and amyloid ß peptide (Aß). The brains of AD patients are under intense oxidative stress. The overproduction of Aß leads to Aß-associated free radical oxidative stress. In this study, the antioxidative and neuronal protective effects of Punica granatum extract were investigated against oxidative stress-induced cytotoxicity in PC12 cells. The ethanol extracts of P. granatum protected PC12 cells from hydrogen peroxide (H2O2-induced oxidative stress. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assays revealed a significant increase in cell viability when oxidatively stressed PC12 cells were treated with the P. granatum extract. To examine the effects of P. granatum on Aß1₋42-induced learning and memory impairment in mice, in vivo behavioral tests were performed. Treatment with the extract of P. granatum increased step-through latency in mice injected with Aß1₋42. The results of this study suggest that the ethanol extract of P. granatum mitigated H2O2-induced oxidative stress in PC12 cells. In addition, the extract inhibited neuronal cell death caused by Aß-induced oxidative stress and Aß-induced learning and memory deficiency.

Inhibitory effects of Terminalia chebula extract on glycation and endothelial cell adhesion.

Terminalia chebula Retz. has been used in India for a long time to treat many diseases, and its extract was reported to have antidiabetic activity in vivo. In this study, T. chebula methanolic extract (TCE) containing 2.7 % chebulic acid was evaluated for its preventive effects against the formation of advanced glycation end products (AGEs) and endothelial cell dysfunction. When the effects of TCE on AGE formation and on protein crossing-linking by glycation with D-threose and lens crystallines were examined, TCE showed inhibitory activity in a dose-dependent manner, and the concentration of 1000 µg/mL presented an activity similar to that of 5 mM aminoguanidine as a positive control. Upon investigating the protective activity of TCE against AGE-induced vascular endothelium dysfunction, human umbilical vein endothelial cells (HUVEC) incubated with 100 µg/mL of AGEs had significantly enhanced reactive oxygen species (ROS) formation, whereas the treatment of T. chebula reduced AGE-induced ROS generation. The incubation of HUVEC with 100 µg/mL of AGEs caused a considerable increase in THP-1 monocytic cell adhesion, but this adhesion was reduced by the treatment of TCE. These results suggest that TCE is a potential agent for alleviating diabetic complications.

Ipomoea batatas attenuates amyloid ß peptide-induced neurotoxicity in ICR mice.

In this study, the protective effects of 17 Korean native plants against amyloid ß peptide (Aß)-induced oxidative stress were screened using the 2',7'-dichlorofluorescin diacetate assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Ipomoea batatas exerted the highest protective effects against oxidative stress and was selected for further investigation. To confirm the protective activity of this extract, the I. batatas extract was fed to ICR mice that had been injected with Aß to induce neuronal deficits. In these experiments, the extract of I. batatas significantly reversed Aß-induced neurotoxicity as assessed by the passive avoidance test, a behavioral experiment. Moreover, I. batatas administration reduced the level of lipid peroxidation and increased catalase activities in biochemical studies using the brain tissue of mice. These results indicate that I. batatas might be beneficial against Alzheimer's disease, especially by limiting oxidative stress in the brain.

In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress.

The protective effects of Taraxacum officinale (dandelion) root against alcoholic liver damage were investigated in HepG2/2E1 cells and ICR mice. When an increase in the production of reactive oxygen species was induced by 300 mM ethanol in vitro, cell viability was drastically decreased by 39%. However, in the presence of hot water extract (TOH) from T. officinale root, no hepatocytic damage was observed in the cells treated with ethanol, while ethanol-extract (TOE) did not show potent hepatoprotective activity. Mice, which received TOH (1 g/kg bw/day) with ethanol revealed complete prevention of alcohol-induced hepatotoxicity as evidenced by the significant reductions of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities compared to ethanol-alone administered mice. When compared to the ethanol-alone treated group, the mice receiving ethanol plus TOH exhibited significant increases in hepatic antioxidant activities, including catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione. Furthermore, the amelioration of malondialdehyde levels indicated TOH's protective effects against liver damage mediated by alcohol in vivo. These results suggest that the aqueous extract of T. officinale root has protective action against alcohol-induced toxicity in the liver by elevating antioxidative potentials and decreasing lipid peroxidation.

Antifibrotic effects of green tea on in vitro and in vivo models of liver fibrosis.

AIM: To examine the protective effect of green tea extract (GT) on hepatic fibrosis in vitro and in vivo in dimethylnitrosamine (DMN)-induced rats. METHODS: HSC-T6, a rat hepatic stellate cell line, was used as an in vitro assay system. Cell proliferation, collagen content, and type 1 collagen expression were examined in activated HSC-T6 cells. Collagen was determined by estimating the hydroxyproline content. In rats with DMN-induced hepatic fibrosis, serum aspartate aminotransferase and alanine aminotransferase concentrations, liver hydroxyproline and lipid peroxides were determined. Pathologic changes were examined by hematoxylin & eosin staining. RESULTS: GT administration prevented the development of hepatic fibrosis in the rat model of DMN-induced liver fibrosis. These results were confirmed both by liver histology and by quantitative measurement of hepatic hydroxyproline content, a marker of liver collagen deposition. Accordingly, inhibition of proliferation, reduced collagen deposition, and type 1 collagen expression were observed in activated HSC-T6 cells following GT treatment. These results imply that GT reduced the proliferation of activated HSC and down regulated the collagen content and expression of collagen type 1, thereby ameliorating hepatic fibrosis. CONCLUSION: This study demonstrates that green tea administration can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis.

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.

Proteomic analysis of the protective effects of Platycodi Radix in liver of chronically alcoholic rats.

In this study, we examined the effect of Platycodi Radix (PR) supplementation in chronically alcoholic rats. Sprague-Dawley rats were divided into three groups: control group (no alcohol), alcohol group (36.8% of total calories), and 0.3% PR group. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased by alcohol treatment, and PR supplementation normalized the AST level. Moreover, alcohol-induced cytochrome P450 2E1 was decreased by PR treatment. Proteomic analysis of liver tissues of alcohol-exposed rats and PR-supplemented rats revealed that 50 different proteins functionally characterized as involved with cytoskeleton regulation, signal transduction, cytokine, apoptosis, and reactive oxygen species metabolism showed significant quantitative changes. The expression levels of glutathione S-transferase mu, Bcl-2-like protein, and peroxiredoxin IV were decreased in the alcoholic group, whereas the levels of these proteins were increased more than threefold in the PR group. However, the expression levels of smooth muscle actin, cytochrome P450 2D, mitogen-activated protein kinase 8, and 3alpha-hydroxysteroid dehydrogenase were increased in the alcohol group and were decreased in the PR group. These data suggest that the antioxidant enzymes may play a protective role against alcohol-induced damage via oxidative stress defense mechanisms induced by PR supplementation.

Effect of anti-histone acetyltransferase activity from Rosa rugosa Thunb. (Rosaceae) extracts on androgen receptor-mediated transcriptional regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa rugosa Thunb. (Rosaceae) has been traditionally used for treatments of diabetes, chronic inflammatory diseases, pain, and anticancer in Korea. AIM OF STUDY: We investigate the inhibitory effect of histone acetyltransferase activity from the methanol extract of stems of Rosa rugosa on androgen receptor-mediated transcriptional regulation. MATERIALS AND METHODS: For the present study, Rosa rugosa methanol extract (RRME) was obtained from stem part of Rosa rugosa using methanol extraction. Histone acetyltransferase assay were performed to measure the inhibitory effect on acetylation, reporter assay, real-time PCR and ChIP assay were performed to measure androgen receptor-mediated transcriptional regulation, and MTT test were performed to measure cell viability. RESULTS: RRME inhibited both p300 and CBP (60-70% at 100 microg/ml) activity. We show RRME mediates agonist-dependent androgen receptor (AR) activation and suppresses antagonist-dependent inhibition. RRME treatment also decreased transcription of AR regulated genes and also reduced histone H3 and AR acetylation in the promoters of prostate-specific antigen (PSA) and beta-2-microglobulin (B2M). Finally, RRME treatment reduced the growth of LNCaP, a human prostate cancer cell line. CONCLUSION: These results demonstrate RRME is a potent HAT inhibitor, which reduced AR and histone acetylation leading to decreased AR-mediated transcription and reduced LNCaP cell growth.

Anti-histone acetyltransferase activity from allspice extracts inhibits androgen receptor-dependent prostate cancer cell growth.

Histone acetylation depends on the activity of two enzyme families, histone acetyltransferase (HAT) and deacetylase (HDAC). In this study, we screened various plant extracts to find potent HAT inhibitors. Hot water extracts of allspice inhibited HAT activity, especially p300 and CBP (40% at 100 microg/ml). The mRNA levels of two androgen receptor (AR) regulated genes, PSA and TSC22, decreased with allspice treatment (100 microg/ml). Importantly, in IP western analysis, AR acetylation was dramatically decreased by allspice treatment.Furthermore, chromatin immunoprecipitation indicated that the acetylation of histone H3 in the PSA and B2M promoter regions was also repressed. Finally, allspice treatment reduced the growth of human prostate cancer cells, LNCaP (50% growth inhibition at 200 microg/ml). Taken together, our data indicate that the potent HAT inhibitory activity of allspice reduced AR and histone acetylation and led to decreased transcription of AR target genes, resulting in inhibition of prostate cancer cell growth.

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.

Protective effects of Platycodi radix on alcohol-induced fatty liver.

The protective effects of Platycodi radix (PR), the root of Platycodon grandiflorum A. DC, on alcohol-induced fatty liver and possible mechanisms involved in this protection were investigated in rats. Administration of PR significantly prevented alcohol-induced elevation of serum and liver lipids. Furthermore, PR treatment normalized hepatic liver fatty acid binding protein (L-FABP) expression and cytochrome P450 2E1 (CYP2E1) activity in alcohol-treated rats. These results suggest that inhibition of CYP2E1 and regulation of L-FABP by PR play an important role in alcohol-induced hepatoprotection.

Ferulic acid supplementation prevents trimethyltin-induced cognitive deficits in mice.

This study's objective was to clarify the ameliorative effects ferulic acid (4-hydroxy-3-methoxycinnamic acid) has against cognitive deficits and ChAT activation in trimethyltin (TMT) induced, memory injured mice following a 28-d ferulic acid treatment. After administering TMT for 3 d, each mouse performed Y-maze and passive avoidance tests to check immediate working memory performance and cognitive function. The results showed that ferulic acid administration attenuated TMT-induced memory injury and a decline in ChAT activity in the mice. This suggests that ferulic acid might be useful for preventing cognitive dysfunction as well as for boosting the activation of ChAT in dementia.

Antioxidative and anti-diabetic effects of amaranth (Amaranthus esculantus) in streptozotocin-induced diabetic rats.

The anti-diabetic and antioxidative effect of amaranth grain (AG) and its oil fraction (AO) was studied in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into four groups after induction of STZ-diabetes: normal control; diabetic control; diabetic-AG supplement (500 g kg(-1) diet); diabetic-AO supplement (100 g kg(-1) diet) and fed experimental diets for 3 weeks. Serum glucose, insulin, activities of serum marker enzymes of liver function and liver cytosolic antioxidant enzymes were measured. The AG and AO supplement significantly decreased the serum glucose and increased serum insulin level in diabetic rats. Serum concentration of liver function marker enzymes, GOT and GPT, were also normalized by AG and AO treatment in diabetic rats. Liver cytosolic SOD and GSH-reductase activities were significantly increased, and catalase, peroxidase and GSH-Px activities were decreased in diabetic rats. AG and AO supplement reverted the antioxidant enzyme activities to near normal values. Hepatic lipid peroxide product was significantly higher, and GSH content was decreased in diabetic rats. However, AG and AO supplement normalized these values. Our data suggest that AG and AO supplement, as an antioxidant therapy, may be beneficial for correcting hyperglycaemia and preventing diabetic complications.