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Bisphenol A (BPA), a plasticizer, is widely believed to cause metabolic disorders. However, an effective intervention is still absent. This study investigated the beneficial effects of Epigallocatechin-3-gallate (EGCG) on insulin resistance and microbial disturbance induced by BPA. The serum glucose, insulin, total triglyceride, and total cholesterol were decreased in BPA-treated mice after the intervention of EGCG. The sensitivity of insulin signals in peripheral tissue was improved by modulating the phosphorylation of IRS-1, Akt, and GSK-3β. In addition, 16S rRNA analysis for fecal microbiota showed the relative abundance of Ruminiclostridium, Blautia, unidentified_Ruminococcaceae, and Candidatus_Saccharimonas were restored by the high dose of EGCG. Furthermore, EGCG increased the concentrations of fecal short-chain fatty acids and protected the gut barrier impaired by BPA. Overall, our results demonstrated the positive effects of EGCG on BPA-induced insulin resistance and gut microbial dysbiosis. The current study provides a potential treatment for the chronic metabolic toxicity of BPA.

Baicalein is a dietary flavonoid that exhibits a variety of intestinal pharmacological activities with limited oral bioavailability. In the present study, the intestinal pharmacokinetics of baicalein was determined by HPLC-ESI-MS/MS and HPLC-PDA analysis. After oral administration, the intestinal concentration of baicalein was peaked at 1 h, and the amount of baicalein in the intestine corresponded to 87%, 45%, and 20% of the administered dose at 1 h, 8 h, and 12 h, respectively. Glucuronidation, sulfation, and methylation metabolites were the major metabolites of baicalein in the small intestine, including duodenum, jejunum, and ileum. Dehydroxylation, sulfation, and methylation metabolites were the major metabolites in the large intestine, including cecum and colon. In vitro, baicalein was transformed into its glucuronidation and methylation metabolites in hepatic and intestinal S9 fraction. The glucuronidation metabolites was hydrolyzed to baicalein by gut microbiota, but the dehydroxylation and methylation metabolites were stable during gut microbiota incubation.In conclusion, the intestinal concentration of baicalein can support its intestinal pharmacological activities, and the present study may provide useful information for understanding the bioactivities of flavonoids with limited systemic bioavailability.

This study was designed to explore the anti-obesity effects of cold-water brewed green tea (CWB-GT) on high-fat diet (HFD)-fed mice. CWB-GT was prepared by brewing tea leaves with 30 ℃ cold water, which contained considerable active ingredients including catechins, gallic acid and theanine. Our data demonstrated that CWB-GT could significantly ameliorate obesity and modulate gut microbiota composition of HFD-fed mice by affecting some specific bacteria. Besides, the expression of lipogenesis-related genes including FAS, HMGR and SREBP-1c in liver was inhibited and the expression of fatty acid oxidation-related genes including PPARα and PGC-1α in adipose tissue was enhanced. These benefits might be attributed to the stimulation of serum peptide YY (PYY) secretion. In particular, specific bacteria modulated by CWB-GT including Lachnospiraceae bacterium DW67, Blautia coccoides, Parabacteroides merdae and Bacteroides_vulgatus might be key mediators in exerting anti-obesity effects. This study suggested that CWB-GT could represent a novel functional low-calorie beverage.

Baicalein, a dietary flavonoid, is the major constituent of Oroxylum indicum and Scutellaria baicalensis which are consumed as teas or dietary supplements in Asia, European, and the United States. The compound exhibits a variety of bioactivities despite its limited bioavailability. In the present work, 4-week treatment of baicalein significantly decreased the levels of blood glucose and circulating lipopolysaccharide (LPS) and improved insulin resistance, inflammation, and lipid profile in diabetic rats induced by STZ and high-fat-high-sugar-diet. These anti-diabetic effects were attributed to the increased SCFAs content and the increased thickness of gut mucus layer, and were associated with the modulation of gut microbiota. Among the key phylotypes, Bacteroides and Bacteroidales S24-7 had the highest relative abundance in the rats receiving high-dose baicalein and showed positive correlation with the phenotypes related to the improvement of type 2 diabetes (T2DM). Our study supports the use of baicalein as a dietary supplement and a potential prebiotic for its ability to modify gut microbiota and to improve T2DM-related biochemical abnormalities.

Baicalein, a major component in Scutellaria baicalensis and Oroxylum indicum, is used as dietary supplement in Asia. In this study, we characterized the insulin-sensitizing activity of baicalein and found that baicalein improved insulin resistance by reducing the expression of SOCS3, increasing the phosphorylation of IRS1 and Akt1, reducing the phosphorylation of GSK3β and increasing hepatic glycogen level. We further evaluated the preventive effect of baicalein combined with acarbose in mice, aiming to enhance the therapeutic effect and reduce the side-effects of acarbose. The combination reduced the relative risk of progression from prediabetes to diabetes by 83.3% and the dose of acarbose by 80%. The underlying mechanisms include reducing postprandial hyperglycemia, improving insulin resistance, improving lipid metabolism, and reducing oxidative stress. Our results suggest that the consumption of 195–780 mg/d baicalein might improve the efficacy of acarbose on diabetes prevention and reduce the side-effects of acarbose in long-term acarbose users.