Gut microbiota-based pharmacokinetic-pharmacodynamic study and molecular mechanism of specnuezhenide in the treatment of colorectal cancer targeting carboxylesterase
作者机构：State Key Laboratory of Bioactive Substance and Function of Natural MedicinesInstitute of Materia MedicaChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing100050China
出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)
年 卷 期：2023年第13卷第9期
页 面：1024-1040页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：supported by the National Key R&D Program of China(Grant No.:2022YFA0806400) the CAMS Innovation Fund for Medical Sciences(Grant Nos.:2022-I2M-1-028,2022-I2M-2-002,and 2021-I2M-1-007) the National Natural Science Foundation of China(Grant Nos.:81973290 and 82173888) Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study,China(Grant No.:Z141102004414062)
主 题：Specnuezhenide Pharmacokinetics Tumor Gut microbiota Fungi Metabolism
摘 要：Specnuezhenide(SNZ)is among the main components of Fructus Ligustri Lucidi,which has antiinflammation,anti-oxidation,and anti-tumor *** low bioavailability makes it difficult to explain the mechanism of pharmacological effect of *** this study,the role of the gut microbiota in the metabolism and pharmacokinetics characteristics of SNZ as well as the pharmacological meaning were *** can be rapidly metabolized by the gut microbiome,and two intestinal bacterial metabolites of SNZ,salidroside and tyrosol,were *** addition,carboxylesterase may be the main intestinal bacterial enzyme that mediates its *** the same time,no metabolism was found in the incubation system of SNZ with liver microsomes or liver homogenate,indicating that the gut microbiota is the main part involved in the metabolism of *** addition,pharmacokinetic studies showed that salidroside and tyrosol can be detected in plasma in the presence of gut ***,tumor development was inhibited in a colorectal tumor mice model administered orally with SNZ,which indicated that SNZ exhibited potential to inhibit tumor growth,and tissue distribution studies showed that salidroside and tyrosol could be distributed in tumor *** the same time,SNZ modulated the structure of gut microbiota and fungal group,which may be the mechanism governing the antitumoral activity of ***,SNZ stimulates the secretion of short-chain fatty acids by intestinal flora in vitro and in *** the future,targeting gut microbes and the interaction between natural products and gut microbes could lead to the discovery and development of new drugs.
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