GEN alleviated NASH as well as hypercholesterolemia and obesity in ApoE(-/-) mice fed an HFD. Restoration of altered cholesterol metabolism and oxidative stress may be involved in the protective effect of GEN against NASH development.

No abstract

Lentinula edodes is one of the most popular edible mushrooms worldwide and contains important medicinal components such as lentinan, ergosterol, and eritadenine. Mushroom metabolism is regulated by the mycelia and fruit body using light; however, in mushrooms, the underlying molecular mechanisms controlling this process as well as light-induced gene expression remain unclear. Therefore, in this study, we compared morphological changes and gene expression in the fruit bodies of L. edodes cultivated under blue light and continuous darkness. Our results showed that blue light primarily induced pileus growth (diameter and thickness) compared to dark cultivation. Alternatively, stipe length development was promoted by dark cultivation. We also performed RNAseq on L. edodes under the blue light/ dark cultivation conditions. A total of 12,051 genes were used for aligning the Illumina raw reads and 762 genes that showed fold change cut-offs of >|2| and significance p-values of <0.05 were selected under blue light condition. Among the genes which showed two-fold changed genes, 221 were upregulated and 541 were downregulated. In order to identify blue light induced candidate genes, differentially expressed genes (DEGs) were selected according to 4-fold changes and validated by RT-PCR. We identified 8 upregulated genes under blue light condition, such as DDR48-heat shock protein, Fasciclin-domain-containing protein and carbohydrate esterase family 4 protein, FAD NAD-binding domain-containing protein that are involved in morphological development of primordium and embryonic muscle development, cell adhesion and affect the structure of cellulosic and non-cellulosic cell walls of fruit body development, and photoreceptor of blue light signaling for fruit body and pigment development, respectively. This study provides valuable insights into the molecular mechanisms underlying the role of blue light in mushroom growth and development and can thus contribute to breeding programs to improve mushroom cultivation.

Nonalcoholic fatty liver disease is a complex disorder which includes simple steatosis, steatohepatitis, fibrosis and ultimately cirrhosis. Previous studies have reported that genistein, a soy phytoestrogen, attenuates steatohepatitis induced in obese and type 2 diabetic models. Here we investigated the effect of dietary genistein supplementation (0.05%) on nonalcoholic steatohepatitis (NASH) development induced by a methionine-choline-deficient (MCD) diet in db/db mice. MCD-diet-fed mice exhibited a significantly lower body weight and a higher degree of steatohepatitis with increased oxidative stress, steatosis, inflammation, stellate cell activation, and mild fibrosis. Although genistein did not inhibit hepatic steatosis, we observed that oxidative stress, endoplasmic reticulum stress, and AMP-dependent kinase inactivation were alleviated by genistein. Genistein also down-regulated the augmented gene expressions associated with hepatic inflammation and fibrosis. Therefore, these results suggest that genistein may protect MCD-diet-mediated NASH development by suppressing lipid peroxidation, inflammation, and even liver fibrosis in db/db mice.

Several studies have demonstrated a protective effect of estrogen against the risk of developing neurodegenerative diseases; however, the molecular mechanisms involved have not been fully addressed. Isoflavones have been proposed as potential alternatives to estrogen replacement therapy. Therefore, in the present study, we investigated effects of isoflavones on cell death and tau phosphorylation in SH-SY5Y human neuroblastoma cells. Cells were treated with tunicamycin (TM) to induce endoplasmic reticulum (ER) stress-mediated toxicity, which is involved in development of neurodegenerative diseases. Treatment of cells with either 17beta-estradiol or isoflavones (either genistein or daidzein) significantly protected cells against cell death. The protective effect against cell death was blocked by a specific estrogen receptor blocker, ICI 182,780, suggesting that isoflavones protect against cell death via estrogen receptor-dependent pathways. Isoflavones also suppressed ER stress as determined by decreased expressions of the immunoglobulin binding protein (BiP) mRNA, spliced X-box binding protein-1 (Xbp-1) mRNAs, and C/EBP homologous protein (CHOP). TM activated glycogen synthase kinase 3beta (GSK3beta), a kinase involved in tau phosphorylation; in contrast, isoflavones inactivated GSK3beta and decreased tau hyperphosphorylation. In conclusion, our results clearly demonstrate that isoflavones prevent ER stress-mediated neurotoxicity by inhibiting tau hyperphosphorylation in SH-SY5Y cells.