Metabolites identification and species comparison of Oroxylin A, an anti-cancer flavonoid, in vitro and in vivo by HPLC-Q-TOF-MS/MS

Abstract

1. Oroxylin A, the main component of Scutellaria baicalensis Georigi has been widely studied due to its well-known pharmacological effects. According to previous studies, Oroxylin A with low bioavailability was converted into glucuronidation and sulphonated metabolites, which had high exposure in plasma and generated certain activities. It is necessary to study the metabolites and metabolic pathways of Oroxylin A.

2. This study aimed to explore the metabolites of Oroxylin A in liver microsomes, primary hepatocyte incubation samples of five different species (human, monkey, dog, mouse, rat), and in bile, urine and faeces of rats.

3. It would provide a systematic description of metabolic pathway of Oroxylin A. Also, a method of high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry detector (HPLC-Q-TOF-MS/MS) for identification of each metabolite in various biological matrices was developed.

4. This experiment illustrated that phase II metabolites were the main form of Oroxylin A in vitro and in excretion of rats, accompanied with a small amount of phase I metabolites.

5. Furthermore, there were obvious species differences among the metabolism in vitro, especially in phase II. Monkeys and rats may be more suitable for preclinical research than dogs and mice as non-rodent or rodent species.

Keywords:

• Metabolites identification
• Oroxylin A
• species comparison
• Flavonoid
• in vitro and in vivo

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Natural Science Foundation of Jiangsu Province [grant number BK20190557] and National Natural Science Foundation of China [grant number 81503148], [grant number 81473272].