Effects of long-term administration of theasinensin A on healthy C57BL/6J mice: Enhancing the function of epididymal white adipose tissue and regulating the colonic microenvironment.

The effects of theasinensin A (TSA) on healthy C57BL/6J mice were investigated. Results showed that long-term administration of 100 mg/kg body weight/day TSA might be non-toxic to healthy mice based on the unaltered basal biochemical indicators related to glucose and lipid metabolism, inflammatory factors and hepatic injury. On the contrary, TSA stimulated the rate of lipid turnover and browning of white adipose tissues, accelerated the adipocytic energy mobilization, and then reduced the white adipocytic size, ultimately enhancing resistance to obesity in healthy mice. Furthermore, TSA not only up-regulated the expression of mucin, tight junction protein, and short-chain fatty acids receptor, but also regulated the intestinal microbiota by enhancing the typical beneficial microbe Akkermansia muciniphila, thereby modulating the colonic microenvironment. These results suggested that TSA had a potential strengthening effect on the resistance of healthy mice to metabolic disorders, which provides a theoretical basis for the utilization of TSA.

Preparation of theasinensin A and theasinensin B and exploration of their inhibitory mechanism on α-glucosidase.

Theasinensin A (TSA) and theasinensin B (TSB), dimers of tea catechins produced during the processing of oolong tea and black tea, had superior inhibitory effects on α-glucosidase. However, the potential inhibitory mechanisms on α-glucosidase are still unclear. In the present study, TSA and TSB were chemically synthesized and purified, and their inhibitory effects on α-glucosidase and potential mechanisms were investigated. The results showed that TSA and TSB could inhibit the activity of α-glucosidase in a reversible and noncompetitive manner with IC50 values of 6.342 and 24.464 µg mL-1, respectively, which were much lower than that of acarbose. The fluorescence and circular dichroism spectra revealed that TSA and TSB could alter the microenvironment and the secondary structure of α-glucosidase, thereby decreasing the α-glucosidase activity. Molecular docking results indicated that both TSA and TSB had a strong binding affinity to α-glucosidase by hydrophobic interactions and hydrogen bonds. Moreover, the stronger inhibition of TSA on α-glucosidase might be related to the closer binding site to the active site pocket of α-glucosidase.