Yourlocation: Home > News > Effects of chenodeoxycholic acid on human liver microsomes were established by LC-MS /MS technique
In recent years, the frequent occurrence of drug allergic reactions makes Yin Zhihuang especially in the treatment of neonatal jaundice, acute and chronic hepatitis and other severe hepatitis and other treatment, the application of its injection is limited. Most of the pharmacological substances of traditional Chinese medicine need to be catalyzed by the catalytic metabolism of drugs, and may also inhibit or induce the metabolism of drugs, resulting in metabolic interactions between drugs. Uridine diphosphate glucuronide transferase (UGTs) is located in the cell endoplasmic reticulum, is the most important phase II drug metabolism enzyme. They are capable of catalyzing the binding of uridine-5'-diphosphate glucuronic acid (UDPGA) to a variety of lipophilic substrates, which are important routes for the excretion of various exogenous and endogenous substances. Based on the fingerprints of Yinzhihuang Chinese medicine, the chemical products such as phenylpropanoids, flavonoids and their glycosides, anthraquinones and iridoid glycosides and other natural products may affect the metabolic response of UGTs in vivo. Therefore, the study of the interaction between Chinese herbal medicine and UGTs from the perspective of drug metabolic analysis has a certain methodological significance for the safety of Yinzhihuang traditional Chinese medicine preparation. In this paper, the in vitro metabolic incubation system was used to explore the interaction between the important active components of Yinzhihuang and various subtypes of UGT. The main contents of the study were as follows: 1) 9 kinds of probe substrates estradiol, chenodeoxycholic acid, the effects of 9 kinds of UGT on human liver microsomes were established by LC-MS / MS technique. The results showed that there were three kinds of UGT Subunits UGT1A1,1A3,1A4,1A6,1A9,2B7,2B10,2B15 and 2B17 activity analysis method. A method for simultaneous chromatographic analysis of multi - component injection was established and verified. It was found that the traditional method was not feasible to quantify the corresponding metabolites by mass spectrometry of the substrate. 2) The UGT activity screening and evaluation system was established by optimizing the conditions of in vitro incubation, including methylpropionate, monomethyl lactone, magnesium chloride and buffer solution. The effects of 11 components ( Chlorogenic acid, epicatechin, geniposide, luteolin, quercetin, baicalin, scallardolide, emodin and chrysophanol) to nine kinds of UGT subtype enzyme-mediated drug metabolism. We found that epicatechin, quercetin, and baicalin had significant inhibitory effects. It was further confirmed that quercetin and baicalin produced noncompetitive inhibition of UGT1A4 and UGT1A1, respectively. The inhibitory parameters Ki were 11.6 and 59.8 μM. 3) To investigate the catalytic effect of glucuronosyltransferase in human liver microsomes on the contents of hydroxyl groups and carboxyl groups in Yinzhihuang, and to discuss the spatial stereoselectivity of UGT enzyme catalysis on these plant monomers. It was found that UGT enzyme had a catalytic effect on flavonoid glycosides containing one glucoside group, and the catalytic activity of nine UGT isoenzymes was compared. The catalytic efficiency of UGT1A1 was the highest.

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