Protective Role of Dietary Capsanthin in a Mouse Model of Nonalcoholic Fatty Liver Disease.

Capsanthin is the main carotenoid compound in red paprika (Capsicum annuum L.). However, little is known about the beneficial effects of capsanthin in nonalcoholic fatty liver disease (NAFLD). In this study, the hepatoprotective activity of capsanthin was investigated in a mouse model of NAFLD. Apolipoprotein-E knockout mice were fed with normal diet, Western-type diet (WD, NAFLD model), WD with capsanthin (0.5 mg/kg of body weight/day, CAP), WD with capsanthin-rich extract (25 mg/kg of body weight/day; CRE), or WD with red paprika powder (25 mg/kg of body weight/day, RPP) for 12 weeks. The carotenoid content in CRE or RPP was analyzed using ultraperformance liquid chromatography. The capsanthin concentration in CRE was 2067 mg/100 g of dry weight, which was 63% of total carotenoids. The oral administration of CRE or capsanthin significantly reduced the WD-induced increase in body weight and lipid accumulation in the liver (vs. the RPP group). In addition, CRE or capsanthin significantly inhibited the WD-induced increase in cholesterol and low-density lipoprotein levels. Furthermore, CRE or capsanthin showed reduced levels of plasma alanine and aspartate aminotransferase (ALT and AST, respectively), suggesting a steatohepatitis protective effect. Capsanthin regulated mRNA levels of peroxisome proliferator-activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), acyl-CoA oxidase 1 (Acox1), and sterol regulatory element binding protein-1c (Srebp1c), which are associated with hepatic fatty acid metabolism. Overall, our results suggest that the capsanthin of red paprika plays a protective role against hepatic steatosis/steatohepatitis in NAFLD.

Anthocyanin-Rich Extract from Red Chinese Cabbage Alleviates Vascular Inflammation in Endothelial Cells and Apo E-/- Mice.

Anthocyanins, the most prevalent flavonoids in red/purple fruits and vegetables, are known to improve immune responses and reduce chronic disease risks. In this study, the anti-inflammatory activities of an anthocyanin-rich extract from red Chinese cabbage (ArCC) were shown based on its inhibitory effects in cultured endothelial cells and hyperlipidemic apolipoprotein E-deficient mice. ArCC treatment suppressed monocyte adhesion to tumor necrosis factor-α-stimulated endothelial cells. This was validated by ArCC's ability to downregulate the expression and transcription of endothelial adhesion molecules, determined by immunoblot and luciferase promoter assays, respectively. The regulation of adhesion molecules was accompanied by transcriptional inhibition of nuclear factor-κB, which restricted cytoplasmic localization as shown by immunocytochemistry. Administration of ArCC (150 or 300 mg/kg/day) inhibited aortic inflammation in hyperlipidemic apolipoprotein E-deficient mice, as shown by in vivo imaging. Immunohistochemistry and plasma analysis showed that the aortas from these mice exhibited markedly lower leukocyte infiltration, reduced plaque formation, and lower concentrations of blood inflammatory cytokines than those observed in the control mice. The results suggest that the consumption of anthocyanin-rich red Chinese cabbage is closely correlated with lowering the risk of vascular inflammatory diseases.

Ethanol Extract of Brassica rapa ssp. pekinensis Suppresses Tumor Necrosis Factor-α-Induced Inflammatory Response in Human Umbilical Vein Endothelial Cells.

Brassica rapa L. ssp. pekinensis, commonly known as Chinese cabbage, is a cruciferous vegetable traditionally consumed in east Asia. Although its habitual consumption could account for the low incidence of chronic vascular inflammation, the therapeutic and protective potential of phytochemicals derived from Chinese cabbage has been poorly studied. In this study, we identified the phenolic compounds, kaempferol and quercetin, from the ethanol extract of Chinese cabbage (EtCC). We show for the first time that EtCC contains effective phytochemicals that suppress tumor necrosis factor (TNF)-α-induced inflammatory response in human umbilical vein endothelial cells. The EtCC inhibited TNF-α-induced monocyte adhesion to endothelial cells in a dose-dependent manner. The antiadhesive activity of EtCC directly correlated with downregulation of expression and transcription of vascular cell adhesion molecule-1 (VCAM-1). It was caused by an Nrf-2-dependent mechanism, leading to activation of antioxidant responsive element-driven promoter. Taken together, these results suggest that EtCC inhibits the expression of TNF-α-induced adhesion molecules through the indirect transcriptional modulation of VCAM-1 in endothelial cells. In conclusion, regular consumption of vegetables containing dietary phytochemicals might be a potential therapeutic strategy to protect against various stresses, to prevent several pathological conditions, and to treat chronic vascular inflammation, such as atherosclerosis.

Ulmus davidiana ethanol extract inhibits monocyte adhesion to tumor necrosis factor-alpha-stimulated endothelial cells.

BACKGROUND: Ulmus davidiana var. japonica Rehder (UD) has long been used in traditional folk medicine in Asia. This study is designed to investigate the antiadhesive activity of the ethanol extract of UD (UDE) and its underlying mechanisms in cultured endothelial cells. METHODS: The dried root bark of UD was extracted with 80% (v/v) ethanol. The antiadhesive activity of the UDE was investigated in cultured human umbilical vein endothelial cells and human embryonic kidney epithelial 293T (HEK 293T) cells stably transfected with pGL3-vascular cell adhesion molecule (VCAM)-1-luc. Monocyte adhesion in endothelial cells was induced by tumor necrosis factor-alpha (TNF-α), and the protective effects of UDE on monocyte-endothelial cell adhesion, VCAM-1 expression, reactive oxygen species production, and nuclear factor-κB activity were determined. RESULTS: Exposure to UDE at a concentration of 3-30 µg/mL for 24 hours produced no detectable cytotoxicity in human umbilical vein endothelial cells, but it significantly inhibited TNF-α-induced monocyte adhesion and VCAM-1 expression. TNF-α treatment of HEK 293T/VCAM-1-luc cells resulted in increased luciferase activity of the VCAM-1 promoter, which was inhibited by treatment with UDE. Additionally, TNF-α-induced reactive oxygen species generation, nuclear translocation of nuclear factor-κB, and IκBα degradation in human umbilical vein endothelial cells were effectively reduced by treatment with 30 µg/mL of UDE. CONCLUSION: Our results indicated that UDE treatment inhibited TNF-α-induced monocyte adhesion in endothelial cells, suggesting that UD may reduce vascular endothelial inflammation.

The hexane fraction of Naematoloma sublateritium extract suppresses the TNF-α-induced metastatic potential of MDA-MB-231 breast cancer cells through modulation of the JNK and p38 pathways.

Naematoloma sublateritium (Fr.) P. Karst is a basidiomycete that has been used as traditional medicine. N. sublateritium produces a triterpenoid antitumor compound, clavaric acid, but, in general, the effects of N. sublateritium constituents against tumor invasion and metastasis have been poorly studied. To investigate the inhibitory effect of N. sublateritium constituents on highly invasive and metastatic tumor cells, the TNF-α-stimulated human breast cancer cell line, MDA-MB­231 was treated with the hexane fraction of an N. sublateritium extract (HFNS). Non-cytotoxic concentrations of HFNS markedly inhibited the invasion and migration of the MDA-MB­231 cells in the Matrigel invasion assay and wound-healing analysis, respectively. Gelatin zymography showed that HFNS suppressed the activity of MMP-9, but not of MMP-2. Immunoblotting demonstrated that treatment with HFNS had decreased the level of MMP-9 and urokinase plasminogen activator-1 (uPA-1), but had upregulated expression of the endogenous inhibitor proteins, including TIMP-1,-2, and PAI-1, in a dose-dependent manner. Furthermore, HFNS suppressed the phosphorylation of p38 and JNK1/2, but not that of ERK1/2. This was confirmed by pretreatment of cells with specific inhibitors prior to stimulation with TNF-α. HFNS treatment also led to a dose-dependent inhibition of the DNA-binding activities of AP-1 and NFκB, which are downstream targets of JNK and p38. These data suggested that HFNS inhibits the metastatic potential of MDA-MB­231 cells by inhibiting the phosphorylation of JNK/p38 and reducing AP-1 and NFκB DNA-binding activities. Therefore, HFNS may be a potential therapeutic agent against metastasis of breast cancer.

A standardized bamboo leaf extract inhibits monocyte adhesion to endothelial cells by modulating vascular cell adhesion protein-1.

Bamboo leaves (Phyllostachys pubescens Mazel ex J. Houz (Poacea)) have a long history of food and medical applications in Asia, including Japan and Korea. They have been used as a traditional medicine for centuries. We investigated the mechanism of anti-inflammatory activity of a bamboo leaf extract (BLE) on tumor necrosis factor-alpha (TNF-α)-induced monocyte adhesion in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to BLE did not inhibit cell viability or cause morphological changes at concentrations ranging from 1 µg/ml to 1 mg/ml. Treatment with 0.1 mg/ml BLE caused 63% inhibition of monocyte adhesion in TNF-α-activated HUVECs, which was associated with 38.4% suppression of vascular cell adhesion molecule-1 expression. Furthermore, TNF-α-induced reactive oxygen species generation was decreased to 47.9% in BLE treated TNF-α-activated HUVECs. BLE (0.05 mg/ml) also caused about 50% inhibition of interleukin-6 secretion from lipopolysaccharide-stimulated monocyte. The results indicate that BLE may be clinically useful as an anti-inflammatory or anti-oxidant for human cardiovascular disease including atherosclerosis.