There are four units of high - pressure to ultrahigh - pressure metamorphism extending from south to north across the Tongbai - Dabie Mountains : the epidote- blueschist - fades unit , the low - temperature eclogite f...There are four units of high - pressure to ultrahigh - pressure metamorphism extending from south to north across the Tongbai - Dabie Mountains : the epidote- blueschist - fades unit , the low - temperature eclogite facies unit , the ultrahigh - pressure eclogite facies unit and the medium-temperature eclogite facies unit . The later two units were formed during the Caledonian subduction between the Tongbai - Dabie microplate and the North China plate ;the former two units are the products of Indosinian continental - continental subduction and collision between the Yangtze and the North China plates.展开更多
Lianhuaqingwen(LHQW)capsule,a herb medicine product,has been clinically proved to be effective in coronavirus disease 2019(COVID-19)pneumonia treatment.However,human exposure to LHQW components and their pharmacologic...Lianhuaqingwen(LHQW)capsule,a herb medicine product,has been clinically proved to be effective in coronavirus disease 2019(COVID-19)pneumonia treatment.However,human exposure to LHQW components and their pharmacological effects remain largely unknown.Hence,this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities.Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach,leading to detection of 132 LHQW prototype and metabolite components,which were absorbed via the gastrointestinal tract and formed via biotransformation in human,respectively.Together with data from screening by comprehensive 2 D angiotensin-converting enzyme 2(ACE2)biochromatography,8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation.Results show that rhein,forsythoside A,forsythoside I,neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2.For the first time,this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human.It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.展开更多
基金The study is sponsored by the key project of National Natural Sci-ence Foundation of China and the Laboratory of Crust-Mantle Constitution, Recycling and Dynamics
文摘There are four units of high - pressure to ultrahigh - pressure metamorphism extending from south to north across the Tongbai - Dabie Mountains : the epidote- blueschist - fades unit , the low - temperature eclogite facies unit , the ultrahigh - pressure eclogite facies unit and the medium-temperature eclogite facies unit . The later two units were formed during the Caledonian subduction between the Tongbai - Dabie microplate and the North China plate ;the former two units are the products of Indosinian continental - continental subduction and collision between the Yangtze and the North China plates.
基金supported by Natural Science Foundation of China,China,(Grant Nos.81773688,U1903119,81973291,and 81973275)Zhejiang University Special Scientific Research Fund for COVID-19 Prevention and Control,China+1 种基金“Phospherus”Project of Shanghai Science and Technology Committee,China,(Grant Nos.19QA1411500)National Major Scientific and Technological Special Project for"Significant New Drugs Development",China,(Grant No.2020ZX09201005)
文摘Lianhuaqingwen(LHQW)capsule,a herb medicine product,has been clinically proved to be effective in coronavirus disease 2019(COVID-19)pneumonia treatment.However,human exposure to LHQW components and their pharmacological effects remain largely unknown.Hence,this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities.Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach,leading to detection of 132 LHQW prototype and metabolite components,which were absorbed via the gastrointestinal tract and formed via biotransformation in human,respectively.Together with data from screening by comprehensive 2 D angiotensin-converting enzyme 2(ACE2)biochromatography,8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation.Results show that rhein,forsythoside A,forsythoside I,neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2.For the first time,this study provides chemical and biochemical evidence for exploring molecular mechanisms of therapeutic effects of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human.It also demonstrates the utility of the human exposure-based approach to identify pharmaceutically active components in Chinese herb medicines.
