Orally Administered Diosgenin Alleviates Colitis in Mice Induced by Dextran Sulfate Sodium through Gut Microbiota Modulation and Short-Chain Fatty Acid Generation.

Diosgenin (DIO) is a kind of steroid sapogenin derived from natural plants. It exerts strong anti-infection, antiallergy, antiviral, and antishock pharmacological properties. In this article, the protective effects of DIO against dextran sulfate sodium (DSS)-induced colitis in mice were researched. Compared with the 2.5% DSS treatment group, 15 mg/kg body weight of diosgenin alleviated colitis disease, evidenced by the increased body weight, the decrease in the disease activity index, and the histological scores. Furthermore, 16S rRNA high-throughput sequencing results demonstrated that DIO improved the colon homeostasis through modulating the gut microbiota, including increases in the relative abundance of several probiotic bacteria, such as Prevotellaceae (from 1.4% to 5.8%), Lactobacillus (from 12.3% to 29.7%), Mucispirillum (from 0.07% to 0.49%), and decreases in the pathogenic bacteria, such as Streptococcus (from 1.6% to 0.6%) and Pseudomonadaceae (from 0.004% to 0%). In addition, the concentration of gut microbial metabolites, total short-chain fatty acids (SCFAs), acetic acid, and propionic acid were significantly increased after DIO supplementation. In conclusion, our findings suggested that DIO attenuates DSS-induced colitis in mice by means of modulating imbalanced gut microbiota and increases in SCFA generation.

Nephrotoxicity evaluation of 3-monochloropropane-1,2-diol exposure in Sprague-Dawley rats using data-independent acquisition-based quantitative proteomics analysis.

3-Monochloropropane-1,2-diol (3-MCPD), as a heat-induced food process contaminant, possesses strongly toxic effect on kidney. The present study focuses on characterizing the proteome and clarifying the underlying molecular regulatory mechanisms in a model of kidney injury in rats treated with 3-MCPD. Data-independent acquisition (DIA)-mass spectrometry (MS) based proteomics was used to identify dysregulated proteins in kidney tissues of Sprague-Dawley (SD) rats treated with 30 mg/kg/day 3-MCPD by gavage for 28 days. It was found that a total of 975 proteins were deregulated after 3-MCPD treatment. Bioinformatic analyses revealed that several enzymes related to the metabolisms of amino acid, lipid and carbohydrate in endogenous metabolism were altered in response to 3-MCPD treatment. Moreover, some proteins involved in these pathways were also changed, mainly including oxidative stress, oxidative phosphorylation, apoptosis and autophagy. Our study unravels the vital roles of loss of mitochondrial homeostasis and function and cell death pathways in the development of renal damage induced by 3-MCPD, which provides further valuable insights into the initiation and resolution of 3-MCPD nephrotoxicity. The proposed DIA-MS workflow not only provides a choice for proteomic analysis in toxicological research, but also provides a more comprehensive understanding of the molecular mechanisms of nephrotoxicity induced by toxins.

N-Acetylcysteine Inhibits Patulin-Induced Apoptosis by Affecting ROS-Mediated Oxidative Damage Pathway.

Patulin (PAT) belongs to the family of food-borne mycotoxins. Our previous studies revealed that PAT caused cytotoxicity in human embryonic kidney cells (HEK293). In the present research, we systematically explored the detailed mechanism of ROS production and ROS clearance in PAT-induced HEK293 cell apoptosis. Results showed that PAT treatment (2.5, 5, 7.5, 10 µM) for 10 h could regulate the expression of genes and proteins involved in the mitochondrial respiratory chain complex, resulting in dysfunction of mitochondrial oxidative phosphorylation and induction of ROS overproduction. We further investigated the role of N-acetylcysteine (NAC), an ROS scavenger, in promoting the survival of PAT-treated HEK293 cells. NAC improves PAT-induced apoptosis of HEK293 cells by clearing excess ROS, modulating the expression of mitochondrial respiratory chain complex genes and proteins, and maintaining normal mitochondrial function. In addition, NAC protects the activity of antioxidant enzymes, maintains normal GSH content, and relieves oxidative damage. Additionally, 4 mM NAC alleviated 7.5 µM PAT-mediated apoptosis through the caspase pathway in HEK293 cells. In summary, our study demonstrated that ROS is significant in PAT-mediated cytotoxicity, which provides valuable insight into the management of PAT-associated health issues.