Investigation of metabolism of HN-1 isolated from Millettia pachyloba in vivo and in vitro.
10.19540/j.cnki.cjcmm.20190620.201
- Author:
Cai-Xia DOU
1
;
Xiang QIU
1
;
Li WAN
2
Author Information
1. School of Pharmacy,Chengdu University of Traditional Chinese Medicine Chengdu 611137,China State Key Laboratory of Biotherapy,West China Hospital,Sichuan University Chengdu 610041,China.
2. School of Pharmacy,Chengdu University of Traditional Chinese Medicine Chengdu 611137,China.
- Publication Type:Journal Article
- Keywords:
Millettia pachyloba;
liver microsomes;
metabolic stability;
metabolites
- MeSH:
Animals;
Chromatography, High Pressure Liquid;
Dogs;
Drugs, Chinese Herbal;
Humans;
Mice;
Microsomes, Liver;
Millettia;
Rats;
Rats, Sprague-Dawley;
Tandem Mass Spectrometry
- From:
China Journal of Chinese Materia Medica
2019;44(20):4529-4537
- CountryChina
- Language:Chinese
-
Abstract:
Ultra-fast performance liquid chromatography-mass spectrometry( UFLC-MS/MS) was used to study the anti-inflammatory active ingredient of Millettia pachyloba,6-methoxy-8,8-dimethyl-3-( 2,4,5-trimethoxyphenyl)-4 H,8 H-pyrano[2,3-f]chromen-4-one( HN-1),in liver microsomes of rats,mice,rhesus monkeys,Beagle dogs and humans metabolic stability,and compare the metabolic differences between different species. The metabolic phenotype in human liver microsomes was determined by chemical inhibitor method. Using UPLC-Q-TOF-MS/MS detection method,the in vitro metabolites of various liver microsomes were preliminarily inferred by comparing the samples incubated for 0 min and 60 min in vitro. The metabolites of HN-1 in SD rats were presumed by comparing feces,urine,plasma blanks and samples after administration. The results showed that the metabolism of HN-1 in various liver microsomes was stable,and the metabolic properties of dog and human liver microsomes were the closest. It is mainly catabolized by CYP1 A1,CYP2 D6 and CYP3 A4 isoenzymes in human liver microsomes. The metabolites of HN-1 in vitro and in vivo,including 3 in vitro metabolites and5 in vivo metabolites,were preliminarily estimated. The results laid the foundation for further pharmacological studies of HN-1.
