Siyu Zhai

Auricularia delicate (ADe), an edible fungus belonging to the family Auriculariaceae and order Auriculariales, possesses antimicrobial, hepatoprotective, and antioxidant effects. In this study, after systematic analysis of its composition, ADe was administered to high-fat-diet (HFD)-fed mice to investigate its anti-obesity effect. ADe significantly controlled body weight; alleviated hepatic steatosis and adipocyte hypertrophy; reduced aspartate aminotransferase, total cholesterol, insulin, and resistin; and increased adiponectin levels in HFD-fed mice serum. Based on intestinal microbiota and lipidomics analysis, ADe treatment regulated the composition and abundance of 49 intestinal microorganisms and influenced the abundance of 8 lipid species compared with HFD-fed mice. Based on a correlation analysis of the intestinal microbiota and lipids, Coprococcus showed significant negative associations with ceramide (d18:0 20:0+O), phosphatidylserine (39:4), sphingomyelin (d38:4), and zymosterol (20:2). Moreover, ADe treatment decreased the levels of ROS and MDA and increased the levels of Nrf2, HO-1, and three antioxidant enzymes in HFD-fed mice livers. Collectively, the anti-obesity effect of ADe involves the regulation of oxidative stress and is mediated by the intestinal microbiota. Hence, this study provides a reference for the application of ADe as a candidate food for obesity.

Background: Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer’s disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid β (Aβ)_1–42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. Methods: U251 cells were co-incubated with 10 μM of Aβ_1-42 and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aβ_1-42-damaged U251 cells. Results: In Aβ_1-42-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aβ, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis. Conclusions: The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.

The improper usage of antibiotics is known to cause widespread antibiotic resistance. In this study, the antibacterial effects of a polypeptide-enriched extract from the skin of the amphibian Rana chensinensis (RCP) were evaluated against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus and the fungus Candida albicans. The mechanisms underlying these effects were also studied, and the minimum inhibitory concentration of RCP was determined for each species. Analyses of the levels of adenosine triphosphates (ATPases), including Na⁺/K⁺-ATPase and Ca²⁺-ATPase, and scanning electron microscopy confirmed that RCP damaged the microbial cell walls and membranes. RCP perturbed microbial metabolism and particularly affected the tricarboxylic acid cycle (TCA), suggesting that this agent downregulated the levels of succinate dehydrogenase, malate dehydrogenase and ATPase activity in cells. Furthermore, RCP caused the leakage of genetic material from all four microbial strains. In conclusion, RCP effectively inhibited the growth of Gram-negative and Gram-positive bacteria and a fungal species by disrupting energy metabolic processes.