In vitro comparison of Ethanol Metabolism in Precision Cut Liver Slices from C57Bl/6, Balb/c, DBA/2J and 129S1/SvlmJ Mice and with the Aldeyra Product ADX-629

Alcoholic liver disease (ALD) is common consequence of excessive alcohol consumption [1]. When the liver is damaged by the intake of alcohol, repair mechanisms are deployed, which results in fibrosis or scarring of the liver. Development of this disease is due to the byproducts of ethanol metabolism. These byproducts include acetaldehyde from the metabolism of ethanol and malondialdehyde from the breakdown of cell membranes during injury. An Aldeyra product, ADX-629, is a small molecule that acts as a reactive aldehyde species (RASP) inhibitor. ADX-629 covalently binds free aldehydes, thus diminishing excessive RASP levels. To determine the aldehyde scavenging abilities of ADX-629 in attenuating fatty liver disease, precision cut liver slices (PCLS) were exposed to varying concentrations of ADX-629 as well as 25mM of ethanol. PCLS, which provide a novel in vitro/ex vivo experimental model, were then measured for triglyceride levels and supernatants were analyzed for acetaldehyde levels. It was found that ADX-629 reduced the acetaldehyde levels released from PCLS while also decreasing triglyceride levels. ADX-629 offers promising clinical uses such as in the prevention of fatty liver formation in patients with non-alcoholic steatohepatitis and in the treatment of alcoholic patients by preventing oxidative stress caused by the breakdown of ethanol thereby, preventing ALD.https://digitalcommons.unmc.edu/surp2021/1062/thumbnail.jp

Differential Effects of Whole Red Raspberry Polyphenols and Their Gut Metabolite Urolithin A on Neuroinflammation in BV-2 Microglia

Whole red raspberry polyphenols (RRW), including ellagic acid, and their gut-derived metabolite, urolithin A (UroA), attenuate inflammation and confer health benefits. Although results from recent studies indicate that polyphenols and UroA also provide neuroprotective effects, these compounds differ in their bioavailability and may, therefore, have unique effects on limiting neuroinflammation. Accordingly, we aimed to compare the neuroprotective effects of RRW and UroA on BV-2 microglia under both 3 h and 12 and 24 h inflammatory conditions. In inflammation induced by lipopolysaccharide (LPS) and ATP stimulation after 3 h, RRW and UroA suppressed pro-inflammatory cytokine gene expression and regulated the JNK/c-Jun signaling pathway. UroA also reduced inducible nitric oxide synthase gene expression and promoted M2 microglial polarization. During inflammatory conditions induced by either 12 or 24 h stimulation with LPS, UroA—but not RRW—dampened pro-inflammatory cytokine gene expression and suppressed JNK/c-Jun signaling. Taken together, these results demonstrate that RRW and its gut-derived metabolite UroA differentially regulate neuroprotective responses in microglia during 3 h versus 12 and 24 h inflammatory conditions

Science, Sustainability, and Saving the World Club

After-school club lesson plans to educate grade school students on sustainable practices and inform them of the earth\u27s changing climate

The Effects of Red Raspberry Pulp Polyphenols and their Gut Microbiota-Derived Metabolites, the Urolithins, on High Fat Diet-Induced Obesity

Urolithins are gut metabolites of polyphenols that are produced through microbial metabolism. Red raspberries are rich in a specific polyphenol known as ellagic acid. Research has revealed that urolithins have the potential to improve insulin sensitivity and attenuate triglyceride accumulation. Gordonibacter urolithinfaciens (G. uro) is a specific gut microbe that aids in the conversion of polyphenols to urolithins. Through four distinct groups of mice treated in vivo with varying necessary components for urolithin production, the health benefits of urolithins were analyzed. All mice were exposed to high fat diets and weighed and analyzed weekly. G. uro was administered through the drinking water and was found to persist in the gut throughout the experiment. The mice supplemented with G. uro were leaner than mice in the other groups and had lower blood glucose levels. This G. uro supplementation demonstrated the positive metabolic impacts that urolithins can provide

Differential Effects of Whole Red Raspberry Polyphenols and Their Gut Metabolite Urolithin A on Neuroinflammation in BV-2 Microglia

Whole red raspberry polyphenols (RRW), including ellagic acid, and their gut-derived metabolite, urolithin A (UroA), attenuate inflammation and confer health benefits. Although results from recent studies indicate that polyphenols and UroA also provide neuroprotective effects, these compounds differ in their bioavailability and may, therefore, have unique effects on limiting neuroinflammation. Accordingly, we aimed to compare the neuroprotective effects of RRW and UroA on BV-2 microglia under both 3 h and 12 and 24 h inflammatory conditions. In inflammation induced by lipopolysaccharide (LPS) and ATP stimulation after 3 h, RRW and UroA suppressed pro-inflammatory cytokine gene expression and regulated the JNK/c-Jun signaling pathway. UroA also reduced inducible nitric oxide synthase gene expression and promoted M2 microglial polarization. During inflammatory conditions induced by either 12 or 24 h stimulation with LPS, UroA—but not RRW—dampened pro-inflammatory cytokine gene expression and suppressed JNK/c-Jun signaling. Taken together, these results demonstrate that RRW and its gut-derived metabolite UroA differentially regulate neuroprotective responses in microglia during 3 h versus 12 and 24 h inflammatory conditions