The present study was designed to investigate the pharmacokinetics and tissue distributions of veratric acid following intravenous administration in rats.The concentrations of veratric acid in rat plasma at various times after administrated at doses of 2.5,5,and 10 mg·kg–1 were quantified by HPLC.The tissue distributions of veratric acid at various times after a single intravenous dose of 2.5 mg·kg–1 were also analyzed.The plasma pharmacokinetic parameters at the three doses were as follows:t1/2,(86.23 ± 6.83),(72.66 ± 4.10) and(71.20 ± 2.90) min; C0,(11.10 ± 1.47),(23.67 ± 1.24) and(39.17 ± 3.90) μg·m L–1; and AUC0→∞,(1 240.90 ± 129.14),(2 273.84 ± 132.47) and(3 516.4 ± 403.37) min·μg·m L–1,respectively.The compound was distributed into tissues rapidly and extensively after intravenous administration and was mainly distributed into the liver,heart and kidneys.
The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature.The knowledge of C-glycoside breakdown and synthesis is very limited.Recently,the enzyme Dgp A/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin(daidzein-8-C-glucoside).Here we investigated how puerarin is recognized and oxidized by Dgp A based on crystal structures of Dgp A with or without substrate and biochemical characterization.More strikingly,we found that apart from being a C-glycoside cleaving enzyme,Dgp A/B/C is capable of efficiently converting O-to C-glycoside showing the activity as a structure isomerase.A possible mechanistic model was proposed dependently of the simulated complex structure of Dgp B/C with 3’’-oxo-daidzin and structure-based mutagenesis.Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation,but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.
