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Poly-γ-glutamic acid (PGA) is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Lastly, PGA promoted activation of 5' adenosine monophosphate-activated protein (AMPK) in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study. [ABSTRACT FROM AUTHOR]

We investigated the hepatoprotective effects of the extract of dandelion leaves (EDL) on a murine model of methionine- and choline-deficient (MCD) diet-induced nonalcoholic steatohepatitis (NASH). C57BL/6 mice were fed for 4 weeks with one of the following diets: control diet (Cont), MCD diet (MCD), MCD diet supplemented with EDL at 200 mg/kg body weight•daily (MCD+ D200), and MCD diet supplemented with EDL at 500 mg/kg body weight•daily (MCD+ D500). Hepatic function was assessed by evaluating the following parameters: liver histology; plasma levels of alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and reduced glutathione (GSH); expression levels of TNF-α and IL-6; and levels of caspase-3 and pJNK/JNK protein. Histopathological evaluations revealed that addition of EDL to the MCD diet dampens the severity of the clinical signs of NASH. Moreover, EDL led to a significant decrease in the serum levels of ALT, hepatic TG, and MDA, and in the expression levels of TNF-α, and IL-6; on the contrary, the levels of reduced GSH increased. At the post-transcriptional level, EDL significantly decreased the activation of procaspase-3 to active caspase-3, and the phosphorylation of JNK. These results suggest that the beneficial effects of EDL on NASH are mainly due to its antioxidant and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

The antidiabetic effect of the Citrus junos Tanaka (also known as yuja or yuzu) was examined. Ethanol extract of yuja peel (YPEE) significantly stimulated 2-[N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) uptake in C2C12 myotubes. However, ethanol extract of yuja pulp (YpEE) and water extract of yuja peel (YPWE) or pulp (YpWE) did not stimulate glucose uptake. In addition, peroxisome proliferator-activated receptor gamma (PPAR-γ) and AMP-activated protein kinase (AMPK) activities were increased by YPEE in a dose-dependent manner. Pretreatment of AMPK inhibitor decreased the glucose uptake stimulated by YPEE in C2C12 myotubes. We confirmed the anti-diabetic effect of YPEE in mice fed a high fat-diet (HFD). Compared with control mice on a normal diet (ND), these mice showed increased body weight, liver fat, insulin resistance, triacylglycerol (TG), and total cholesterol content. Addition of 5% YPEE significantly reduced the weight gain and rise in liver fat content, serum triacylglycerol (TG), total cholesterol, and insulin resistance found in mice fed a high-fat diet (HFD). Moreover, YPEE reduced the secretion of HFD-induced adipocytokines such as leptin and resistin. YPEE also resulted in increased phosphorylation of AMPK in muscle tissues. These results suggest that ethanol extract of yuja peel exerts anti-diabetic effects via AMPK and PPAR-γ in both cell culture and mouse models. [ABSTRACT FROM AUTHOR]

This study was designed to evaluate the effects and mechanism of Platycodi radix, having white balloon flower (Platycodon grandiflorum for. albiflorum (Honda) H. Hara) on obesity and insulin resistance. The extracts of Platycodi radix with white balloon flower were tested in cultured cells and administered into mice on a high-fat diet. The Platycodi radix activated the AMPK/ACC phosphorylation in C2C12 myotubes and also suppressed adipocyte differentiation in 3T3-L1 cells. In experimental animal, it suppressed the weight gain of obesemice and ameliorated obesity-induced insulin resistance. It also reduced the elevated circulating mediators, including triglyceride (TG), T-CHO, leptin, resistin, andmonocyte chemotactic protein ( MCP)-1 in obesity. As shown in C2C12 myotubes, the administration of Platycodi radix extracts also recovered the AMPK/ACC phosphorylation in the muscle of obese mice. These results suggest that Platycodi radix with white balloon flower ameliorates obesity and insulin resistance in obese mice via the activation of AMPK/ACC pathways and reductions of adipocyte differentiation. [ABSTRACT FROM AUTHOR]

Genistein is a polyphenolic nonsteroidal isoflavonoid with estrogen-like activity has been shown to have anticancer, antioxidant, and anti-inflammatory activities. Fractalkine is a unique chemokine that functions as a chemoattractant and an adhesion molecule on endothelial cells activated by proinflammatory cytokines. In this study, we investigated the effects of genistein (5-25 μM) on fractalkine expression in human umbilical vein endothelial cells (HUVECs) and on its receptor, CX3CR1, in THP-1 cells in response to treatment with tumor necrosis factor (TNF)- α. TNF-α significantly induced fractalkine expression in endothelial cells. Genistein decreased TNF-α-induced fractalkine expression through suppression of Akt and p38 phosphorylation and NF-κB activities. Genistein also strongly suppressed TNF-α-induced expression of CX3CR1 in monocytes. Genistein suppressed TNF-α-stimulated adhesion of monocytes to HUVECs. Immunohistochemical analysis revealed that genistein suppressed the in vivo lipopolysaccharide (LPS)-induced arterial endothelial fractalkine expression in the heart, kidney, and small intestine. These results suggest that genistein may provide a new pharmacological approach for suppressing fractalkine/CX3CR1-mediated injury under vascular inflammatory conditions. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

IntroductionHypo-high-density lipoprotein cholesterolemia (hypo-HDL-C) contributes to the development of cardiovascular diseases. The hypothesis that the polygenic variants associated with hypo-HDL-C interact with lifestyle factors was examined in 58,701 middle-aged Korean adults who participated in the Korean Genome and Epidemiology Study (KoGES).MethodsParticipants were categorized into the Low-HDL (case; n = 16,980) and Normal-HDL (n = 41,721) groups. The participants in the Low-HDL group were selected using the guideline-based cutoffs for hypo-HDL-C (

Allium tuberosum is widely cultivated in Asian countries and has been reported to be effective for the prevention of certain diseases, including atherosclerosis. The current study was designed to evaluate the inhibitory effects of ethanol extract of Allium tuberosum on histone acetyltransferase activity and non-alcoholic fatty liver disease (hepatic steatosis). The inhibitory effect of a 70% ethanol extract of Allium tuberosum (EAT) on histone acetyltransferase (HAT) activity was evaluated by colorimetric assay and autoradiography. EAT significantly inhibited the activity of histone acetyltransferase in a dose-dependent manner. To examine whether EAT can reduce hepatic steatosis, we used oleic acid (OA)-induced HepG2 cell model of steatosis. EAT 100 and 200 µg/mL, significantly reduced OA-induced lipid accumulation in HepG2 cells. The expression of PPAR-α was also increased by EAT, which did not show significant cytotoxicity until 400 µg/mL concentrations in HepG2 cells. We further demonstrated that OA treatment on HepG2 cell caused a significant increase in histone H3 lysine 9 (H3K9) acetylation. EAT significantly decreased the OA- increased H3K9 acetylation in HepG2 cells. Finally, we also investigated the hypolipidemic effect of EAT using mice fed a high-fat diet (HFD). Administration of 2% EAT significantly reduced the HFD-induced increase in body weight, liver weight, subcutaneous fat, fatty liver and adipose tissue size. These results suggest that Allium tuberosum may be useful for the prevention of hepatic steatosis and is possibly mediated by the inhibition of histone acetylation. [ABSTRACT FROM AUTHOR]

This study investigated the effect and the underlying mechanism of ginseng berry (GB) in a mouse model of type 2 diabetes, supplied with 0.05% or 0.1% dietary GB for 12 weeks. GB significantly improved hyperglycemia and insulin resistance, as demonstrated by the blood glucose and insulin levels, HOMA-IR, and GTT. Moreover, the expression of gluconeogenic genes such as PEPCK and G6Pase and the hepatic metabolites involved in the pathway of gluconeogenesis, such as glucose-6-phosphate and dihydroxyacetone phosphate, were significantly reduced by GB. Hepatic steatosis was also significantly ameliorated; TG content and expression of lipogenic enzymes and transcriptional factors such as FAS, ACC, and SREBP1 were reduced by GB. Simultaneously, AMPK phosphorylation was increased both in fatty liver and in lipid-accumulated HepG2 cells by GB. In conclusion, GB improved hyperglycemia by downregulating hepatic glucose production and hepatic steatosis, and AMPK appeared to be an important regulator of these effects.

Hepatic steatosis is the most common chronic liver disease in Western countries. Both genetic and environmental factors are known as causes of the disease although their underlying mechanisms have not been fully understood. This study investigated the association of DNA methylation with oleic acid-induced hepatic steatosis. It also examined effects of food components on DNA methylation in hepatic steatosis. Genome-wide DNA methylation of oleic acid (OA)-induced lipid accumulation in vitro cell model was investigated using reduced representation bisulfite sequencing. Changes of DNA methylation were also analyzed after treatment with food components decreasing OA-induced lipid accumulation in the model. We identified total 81 regions that were hypermethylated by OA but hypomethylated by food components or vice versa. We determined the expression of seven genes proximally located at the selected differentially methylated regions. Expression levels of WDR27, GNAS, DOK7, MCF2L, PRKG1, and CMYA5 were significantly different between control vs OA and OA vs treatment with food components. We demonstrated that DNA methylation was associated with expression of genes in the model of hepatic steatosis. We also found that food components reversely changed DNA methylation induced by OA and alleviated lipid accumulation. These results suggest that DNA methylation is one of the mechanisms causing the hepatic steatosis and its regulation by food components provides insights that may prevent or alleviate lipid accumulation.

The inhibitory effects of yuja peel extract (Citrus junos Tanaka) on experimental colitis and colorectal cancer cells were evaluated. Yuja peel extracted with 70% ethanol (YPEE) reduced LPS-induced secretion of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and interleukin-6 (IL-6) by reduction of cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), and p38 phosphorylation in RAW264.7 cells. YPEE at 100 mg/(kg·day) also reduced both disease activity index (DAI) and colon shortening induced by Dextran sulphate sodium (DSS) in mice. COX-2 expression was decreased in colon tissue by YPEE. In addition, YPEE induced apoptotic body appearance in HT-29 colorectal cancer cells via decreasing COX-2. Furthermore, YPEE at 100 mg/(kg·day) inhibited tumour growth in tumour xenografts, which was accompanied by reduced COX-2 expression in colon tissue. Taken together, Yuja may be useful in preventing colitis and colorectal cancer via reduction of COX-2 expression.

Equol is a nonsteroidal estrogen metabolized from the soy isoflavone daidzein by intestinal bacteria. Although its clinical benefits remain unclear, many reports have demonstrated that equol plays various biological roles in cancer, osteoporosis, and cardiovascular disease. Contrary to reports in other systems, the function of equol in the olfactory system has not been well understood. In the olfactory system, various odorants can bind to their receptors on olfactory sensory neurons and subsequently activate adenylyl cyclase (AC). Increased cAMP levels via the activated AC modulate Ca2+ influx and lead to altered membrane potential. This process results in transmission of electric signals to the brain. Because cAMP signal transduction and Ca2+ levels play crucial roles in the olfactory system, we investigated the effects of equol on the cAMP pathway and Ca2+ influx after stimulation by the odorant eugenol in gastric adenocarcinoma cells. Our results reveal that the upregulated cAMP level by eugenol was significantly decreased by equol treatment. Phosphorylation of PKA and CREB, downstream targets of cAMP, was also reduced. Furthermore, the odorant-induced Ca2+ levels were decreased in the presence of equol. Taken together, these data suggest that equol inhibits the odorant-induced signaling pathway through modulation of PKA/CREB signaling transduction. [ABSTRACT FROM AUTHOR]

Angiogenesis, the growth of new blood vessels from an existing capillary bed, is a critical homeostatic mechanism, which regulates vascular endothelial cell populations in response to various physiological requirements and pathophysiological demands. Since the relevance of angiogenesis in gastrointestinal chronic inflammation and cancer has been demonstrated, inhibition of angiogenesis is an attractive strategy for the treatment of inflammatory bowel disease, colon cancer, and breast cancer. Here, we attempt to identify phytochemical that contributes to the well-documented preventive effects of plant-based diets on cancer incidence and mortality. We describe biochanin A as a putative antiangiogenic phytochemical that inhibits angiogenesis in human umbilical vascular endothelial cells (HUVECs). Treatment with 100 μM biochanin A inhibited vascular endothelial growth factor (VEGF)-induced migration of HUVECs by up to 60% in a dose-dependent manner. VEGF-induced tube formation of HUVECs was also inhibited by biochanin A. In HUVECs, VEGF treatment increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). However, pretreatment of HUVECs with 100 μM biochanin A decreased phosphorylation of Akt and eNOS. These results showed that biochanin A is, at least, a putative anti-angiogenic phytochemical that regulates the Akt-eNOS signaling pathway. [ABSTRACT FROM AUTHOR]