Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease which seriously affects public health. Gut microbiota remains a dynamic balance state in healthy individuals, and its disorder may affect health status and even results in metabolic diseases. Quercetin, a natural flavonoid, has been shown to have biological activities that can be used in the prevention and treatment of metabolic diseases. This study aimed to explore the mechanism of quercetin in alleviating T2DM based on gut microbiota. db/db mice were adopted as the model for T2DM in this study. After 10 weeks of administration, quercetin could significantly decrease the levels of body weight, fasting blood glucose (FBG), serum insulin (INS), the homeostasis model assessment of insulin resistance (HOMA-IR), monocyte chemoattractant protein-1 (MCP-1), D-lactic acid (D-LA), and lipopolysaccharide (LPS) in db/db mice. 16S rRNA gene sequencing and untargeted metabolomics analysis were performed to compare the differences of gut microbiota and metabolites among the groups. The results demonstrated that quercetin decreased the abundance of Proteobacteria, Bacteroides, Escherichia-Shigella and Escherichia_coli. Moreover, metabolomics analysis showed that the levels of L-Dopa and S-Adenosyl-L-methionine (SAM) were significantly increased, but 3-Methoxytyramine (3-MET), L-Aspartic acid, L-Glutamic acid, and Androstenedione were significantly decreased under quercetin intervention. Taken together, quercetin could exert its hypoglycemic effect, alleviate insulin resistance, repair the intestinal barrier, remodel the intestinal microbiota, and alter the metabolites of db/db mice.

Several studies have found that sleep deprivation (SD) can lead to neuronal ferroptosis and affect hippocampal function. However, there are currently no effective interventions. Vitamin B₆ is a co-factor for key enzymes in the transsulfuration pathway which is critical for maintaining cell growth in the presence of cysteine deprivation. The results showed that SD inhibited cystine-glutamate antiporter light chain subunit xCT protein expression and caused cysteine deficiency, which reduced the synthesis of the glutathione (GSH) to trigger neuronal ferroptosis. Nissl staining further revealed significant neuronal loss and shrinkage in the CA1 and CA3 regions of the hippocampus in SD mice. Typical ferroptotic indicators characterized by lipid peroxidation and iron accumulation were showed in the hippocampus after sleep deprivation. As expected, vitamin B₆ could alleviate hippocampal ferroptosis by upregulating the expression of cystathionine beta-synthase (CBS) in the transsulfuration pathway, thereby replenishing the intracellular deficient GSH and restoring the expression of GPX4. Similar anti-ferroptotic effects of vitamin B₆ were demonstrated in HT-22 cells treated with ferroptosis activator erastin. Furthermore, vitamin B₆ had no inhibitory effect on erastin-induced ferroptosis in CBS-knockout HT22 cells. Our findings suggested chronic sleep deprivation caused hippocampal ferroptosis by disrupting the cyst(e)ine/GSH/GPX4 axis. Vitamin B₆ alleviated sleep deprivation-induced ferroptosis by enhancing CBS expression in the transsulfuration pathway.

Background: Epidemiological evidence for the relationship between riboflavin intake and bone health is inconsistent, and this relationship has not been examined in Chinese population. This study aimed to investigate the relationship between dietary intake of riboflavin and prevalence of osteoporosis in a Chinese adult population.Methods: A total of 5,607 participants (mean age, 61.2 years; males, 34.4%) were included in this cross-sectional study. We calculated the riboflavin intake by using the food frequency questionnaire (FFQ) in combination with Chinese food composition database. Bone mineral density (BMD) was detected by an ultrasound bone densitometer. Multivariable logistic regression models were used to evaluate the relationship between dietary riboflavin intake and prevalence of osteoporosis.Results: In this population, the dietary intake of riboflavin ranged from 0.13 to 1.99 mg/d, and the proportion of abnormal BMD was 36.6%. The prevalence of osteoporosis decreased gradually with increasing quartiles of riboflavin intake, before and after adjustment for a range of confounding factors. In the final model, the multivariate-adjusted ORs (95% CI) across the quartiles of riboflavin intake were 1.00 (reference), 0.84 (0.54, 1.31), 0.59 (0.34, 1.04), and 0.47 (0.22, 0.96), respectively (P for trend < 0.05). In sex-disaggregated analysis, similar results to the total population were observed in women, while no significant results were found in men.Conclusion: The dietary riboflavin intake was negatively associated with the prevalence of osteoporosis. However, the association was significant in women but not in men. Our findings indicated that women are more sensitive to riboflavin intake in maintaining a normal BMD.