Inhibition of Escherichia coli nitroreductase by the constituents in Syzygium aromaticum  

作　　者：CHEN Lu CHEN Xi BAI Yue ZHAO Zi-Nan CAO Yun-Feng LIU Li-Kun JIANG Tao HOU Jie 

机构地区：[1]College of Basic Medical Sciences,Dalian Medical University,Dalian 116044,China [2]Dalian Runsheng Kangtai Medical Laboratory Co.,Ltd.,Dalian 116000,China

出　　处：《Chinese Journal of Natural Medicines》2022年第7期506-517,共12页中国天然药物（英文版）

基　　金：supported by the Natural Science Foundation of Liaoning Province(No.20180530025);the Innovative Entrepreneurship Program of High-level Talents in Dalian(No.2017RQ121);the Technology Innovation Foundation of Dalian(No.2020JJ26SN051);the National Natural Science Founding of China(No.82160739).

摘　　要：Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds,hydroxylamines or aromatic amines,most of which are carcinogenic and mutagenic agents.Inhibition of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon,so as to prevent colon diseases.In this study,the inhibitory effects of 55 herbal medicines against Escherichia coli(E.coli)nitroreductase(EcNfsA)were examined.Compared with other herbal extracts,Syzygium aromaticum extract showed superior inhibitory potency toward EcNf-sA mediated nitrofurazone reduction.Then,the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were evaluted.Compared with other tested natural compounds,ellagic acid,corilagin,betulinic acid,oleanic acid,ursolic acid,urolith-in M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA,with IC50 values ranging from 0.67 to 28.98 mol·L^(−1).Furthermore,the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA(Ki<2μmol·L−1)in a competitively inhibitory manner,which created strong interactions with the catalytic triad of EcNfsA.In summary,our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum,where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacteri-al nitroreductase.

关 键 词：Gut bacterial nitroreductase EcNfsA inhibitor Syzygium aromaticum Anti-mutagenic activity 

分 类 号：R965[医药卫生—药理学]