Mulberry and dandelion water extracts prevent alcohol-induced steatosis with alleviating gut microbiome dysbiosis.[Pubmed: 30105955]

Chronic alcohol intake causes hepatic steatosis and changes the body composition and glucose metabolism. We examined whether water extracts of mulberry (WMB) and white flower dandelion ( Taraxacum coreanum Nakai, WTC) can prevent and/or delay the symptoms of chronic ethanol-induced hepatic steatosis in male Sprague Dawley rats, and explored the mechanisms. Ethanol degradation was examined by orally administering 3 g ethanol/kg bw after giving them 0.3 g/kg bw WMB or WTC. All rats were continuously provided about 7 g ethanol/kg bw/day for four weeks and were given either of 0.1% dextrin (control), WMB, WTC, or water extracts of Hovenia dulcis Thunb fruit (positive-control) in high-fat diets. Area under the curve of serum ethanol levels was lowered in descending order of control, WTC and positive-control, and WMB in acute ethanol challenge. WMB and WTC prevented alcohol intake-related decrease in bone mineral density and lean body mass compared to the control. After glucose challenge, serum glucose levels increased more in the control group than other groups in the first part and the rate of decrease after 40 min was similar among all groups. These changes were associated with decreasing serum insulin levels. WMB had the greatest efficacy for decreasing triglyceride and increasing glycogen deposits. WMB and WTC prevented the disruption of the hepatic cells and nuclei while reducing malondialdehyde contents in rats fed alcohol, but the prevention was not as much as the normal-control. The ratio of Firmicutes to Bacteroidetes in the gut was much higher in the control than the normal-control, but WTC and WMB decreased the ratio compared to the control. WMB and WTC separated the gut microbiota community from the control. In conclusion, WMB and WTC protected against alcoholic liver steatosis by accelerating ethanol degradation and also improved body composition and glucose metabolism while alleviating the dysbiosis of gut microbiome by chronic alcohol intake. Impact statement Excessive alcohol consumption is associated with serious pathologies and is common in much of the world. Pathologies include liver damage, glucose intolerance, and loss of lean body mass and bone mass. These pathologies are mediated by changes in metabolism as well as toxic metabolic byproducts, and possibly by gut dysbiosis. In this study, we demonstrate that aqueous extracts of mulberry and dandelion protected rats against ethanol-induced losses in lean body and bone masses, improved glucose tolerance and partially normalized gut bacterial populations, with mulberry extract being generally more effective. This research suggests that mulberry and dandelion extracts may have the potential to improve some of the pathologies associated with excess alcohol consumption, and that further clinical research is warranted.

Hovenia dulcis Thunb. and its active compound ampelopsin inhibit angiogenesis through suppression of VEGFR2 signaling and HIF-1α expression.[Pubmed: 29039561]

Specific inhibition of angiogenesis has been considered a powerful strategy for the treatment of cancer and other angiogenesis-related human diseases. Hovenia dulcis Thunb., Japanese raisin tree or Oriental raisin tree, is a hardy tree found in Asia, Eastern China and Korea and has been known to possess various biological activities, including antifatigue, antidiabetic, neuroprotective and hepatoprotective activity. In the present study, for the first time, we evaluated whether a 100% ethanol extract of Hovenia dulcis Thunb. (HDT) inhibits the angiogenesis of human umbilical vein endothelial cells (HUVECs) using in vitro angiogenesis assays. HDT suppressed vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion and tube formation of HUVECs at subtoxic doses. In addition, HDT significantly inhibited in vivo angiogenesis of the chorioallantoic membrane from growing chick embryos without exhibiting cytotoxicity. Furthermore, HDT downregulated not only VEGF receptor 2 (VEGFR2) signaling in HUVECs, but also hypoxia-inducible factor (HIF)-1α expression in hepatocarcinoma cell line HepG2. Ampelopsin is a bioactive flavanonol found in Hovenia dulcis Thunb. Our data showed that ampelopsin inhibited angiogenesis with no cytotoxicity by suppressing both VEGFR2 signaling and HIF-1α expression. These results suggest that Hovenia dulcis Thunb. and its active compound ampelopsin exhibit potent antiangiogenic activities and therefore could be valuable for the prevention and treatment of angiogenesis-related diseases including cancer.

A standardized extract of the fruit of Hovenia dulcis alleviated alcohol-induced hangover in healthy subjects with heterozygous ALDH2: A randomized, controlled, crossover trial.[Pubmed: 28750942]

Hovenia dulcis, known as the oriental raisin tree, is mainly found in East Asia. It has long been used as traditional folk remedies for alcohol intoxication.

Structural elucidation of a pectin-type polysaccharide from Hovenia dulcis peduncles and its proliferative activity on RAW264.7 cells.[Pubmed: 28715863]

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Ceanothane- and lupane-type triterpene esters from the roots of Hovenia dulcis and their antiproliferative activity on HSC-T6 cells.[Pubmed: 28686899]

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Anti-steatotic and anti-inflammatory effects of Hovenia dulcis Thunb. extracts in chronic alcohol-fed rats.[Pubmed: 28380415]

The anti-steatotic and anti-inflammatory effects of fruit water extract (FW) and seed ethanol extract (SE) of Hovenia dulcis Thunb. in chronic alcohol-fed rats were investigated. Rats were fed a liquid diet containing 36% calories from alcohol and orally administered FW or SE (300 and 500mg/kg/day). Both FW and SE reduced hepatic lipid contents and droplets, serum lipid concentration and inflammatory markers (hs-CRP, TNF-α and IL-6) levels compared with the alcohol control group. Alcohol led to significant decreases in the hepatic fatty acid oxidative gene (Ppargc1a, Cpt1a and Acsl1) levels, while it significantly increased the Myd88 and Tnfa gene levels. However, FW or SE supplementation significantly up-regulated gene expression of Ppargc1a, Ppara, Cpt1a and Acsl1, and down-regulated gene expression of Myd88, Tnfa and Crp compared with the alcohol control group. FW or SE supplementation also significantly decreased hepatic activities of fatty acid synthase and phosphatidate phosphohydrolase in chronic alcohol-fed rats. Plasma alcohol and acetaldehyde levels, hepatic enzyme activity and protein expression of CYP2E1 were lowered by FW or SE supplementation. These results indicate that both FW and SE play an important role in improvement of alcoholic hepatic steatosis and inflammation via regulation of lipid and inflammation metabolism.

Evaluation of Total Flavonoids, Myricetin, and Quercetin from Hovenia dulcis Thunb. As Inhibitors of α-Amylase and α-Glucosidase.[Pubmed: 27787697]

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Hovenia Dulcis Extract Reduces Lipid Accumulation in Oleic Acid-Induced Steatosis of Hep G2 Cells via Activation of AMPK and PPARα/CPT-1 Pathway and in Acute Hyperlipidemia Mouse Model.[Pubmed: 27762456]

Hovenia dulcis Thunb. (HDT) was known to have anti-fatigue, anti-diabetes, neuroprotective, and hepatoprotective effects. In the present study, the anti-fatty liver mechanism of HDT was elucidated in oleic acid (OA)-treated Hep G2 cells and acute hyperlipidemia mouse model using Triton WR-1339. Here, HDT activated p-AMP-activated protein kinase (p-AMPK), proliferator activated receptor-α, carnitine palmitoyltransferase and also inhibited the expression of lipogenesis and cholesterol synthesis proteins, such as 3-hydroxy-3-methylglutaryl-CoA reductase, sterol regulatory element binding protein-1c, SREBP-2, and fatty acid synthase in OA-treated Hep G2 cells. Conversely, AMPK inhibitor compound C blocked the anti-fatty liver effect of HDT to induce AMPK phosphorylation and decrease 3-hydroxy-3-methylglutaryl-CoA reductase and lipid accumulation by oil red O staining in OA-treated Hep G2 cells. Additionally, HDT pretreatment protected against the increase of serum total cholesterol, triglyceride, low-density lipoprotein cholesterol and phospholipid in an acute hyperlipidemia mouse model with enhancement of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase activities. Taken together, HDT inhibits OA-induced hepatic lipid accumulation via activation of AMPK and proliferator activated receptor-α/carnitine palmitoyltransferase signaling and enhancement of antioxidant activity as a potent candidate for nonalcoholic fatty liver disease and hyperlipidemia.