Discovery of pulmonary fibrosis inhibitor targeting TGF-b RI in Polygonum cuspidatum by high resolution mass spectrometry with in silico strategy  

作　　者：Huarong Xu Jiameng Qu Jian Wang Kefei Han Qing Li Wenchuan Bi Ran Liu 

机构地区：[1]National and Local Joint Engineering Laboratory for Key Technology of Chinese Material Medica Quality Control,School of Pharmacy,Shenyang Pharmaceutical University,Shenyang,110016,China [2]School of Traditional Chinese Material Medica,Shenyang Pharmaceutical University,Shenyang,110016,China [3]Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education,Shenyang Pharmaceutical University,Shenyang,110016,China [4]Health Science Center Department of Pharmacy,Shenzhen University,Shenzhen,Guangdong,518118,China

出　　处：《Journal of Pharmaceutical Analysis》2022年第6期860-868,共9页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:81703463 and 81603277);the National Key R&D Program of China(Grant No.:U1508220);the Liaoning Distinguished Professor Project for Qing Li,and the Doctoral Scientific Research Foundation of Liaoning Province(Grant No.:20170520199).

摘　　要：Pulmonary fibrosis(PF)is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2-3 years.The inhibition of transforming growth factor-β receptor type-I(TGF-β RI)by an appropriate drug may provide a promising strategy for the treatment of this disease.Polygonum cuspidatum(PC)is a well-known traditional Chinese herbal medicine which has an anti-PF effect.Accordingly,a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI.Based on this strategy,a total of 24 ingredients were identified.Then,absorption,distribution,metabolism,and excretion(ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour.Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors.Eventually,a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI,with an IC_(50) of 2.211 μM in vitro.Furthermore,the complex formed through molecular docking was tested via molecular dynamics simulations,which revealed that resveratrol had strong interactions with residues of TGF-β RI.This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI.In addition,this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.

关 键 词：Polygonum cuspidatum Pulmonary fibrosis TGF-βreceptor type-I RESVERATROL High resolution mass spectrometry Molecular docking 

分 类 号：R962[医药卫生—药理学]