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Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening

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Acta Pharmaceutica Sinica B 2021年第1期11卷 222-236页

作者： Xiaofei Chen Yunlong Wu Chun Chen Yanqiu Gu Chunyan Zhu Suping Wang Jiayun Chen Lei Zhang Lei Lv Guoqing Zhang Yongfang Yuan Yifeng Chai Mingshe Zhu Caisheng Wu School of Pharmacy Naval Medical UniversityShanghai 200433China Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiamen 361102China Department of Pharmacy Shanghai Ninth People’s HospitalShanghai Jiao Tong UniversityShanghai 201999China Department of Pharmacy Shanghai Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200438China MassDefect Technologies PrincetonNJ 08540USA

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.

关键词： lianhuaqingwen capsule PATBS COVID-19 ACE2 Biochromatography Comprehensive 2D analysis In vivo exposure Surface plasma response Molecular docking

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Natural herbal medicine lianhuaqingwen capsule anti-influenza A （H1N1） trial： a randomized, double blind, positive controlled clinical trial

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Chinese Medical Journal 2011年第18期124卷 2925-2933页

作者： DUAN Zhong-ping JIA Zhen-hua ZHANG Jian LIU Shuang CHEN Yu LIANG Lian-chun ZHANG Chang-qing ZHANG Zong SUN Yan ZHANG Shu-qin WANG Yong-yan WU Yi-ling Beijing You-An Hospital Capital Medical University Beijing 100069 China Key Research Centre of Collateral Disease of State Administration of Traditional Chinese Medicine Yiling Pharmaceutical Research Academy of Hebei Province Shijiazhuang Hebei 050035 China Kaifeng Infectious Disease Hospital Kaifeng Henan 415001 China Jinan Infectious Disease Hospital Jinan Shandong 250021 China Henan Provincial Infectious Disease Hospital Zhengzhou Henan 450005 China Jilin Provincial Hepatopathy Hospital Changchun Jilin 130061China China Academy of Chinese Medical Sciences Beijing 100700China

Background The 2009 influenza A （H1N1） virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine lianhuaqingwen capsule （LHC） in patients infected with influenza A （H1N1） virus. Methods A total of 244 patients aged 16-65 years confirmed with influenza A （H1N1） virus infection by the real time RT-PCR were randomized to one of two treatment groups of 122 patients each. Each group assigned to receive either LHC or Oseltamivir for five days and observation for seven days. The patients were enrolled within 36 hours of illness onset if they had an axillary temperature of ≥37.4℃ and with at least one of the following symptoms： nasal obstruction, runny nose, cough, sore throat, fatigue, headache, myalgia, chills and sweating. The primary end point was the duration of illness. Results Of 244 patients, 240 （98.36%） patients with a median age 21 years completed the study between October 24, 2009 and November 23, 2009. There were no significant overall differences between LHC treated and Oseltamivir treated patients in the median duration of illness （LHC 69 hours vs. Oseltamivir 85 hours P 〉0.05） or the median duration of viral shedding （LHC 103 hours vs. Oseltamivir 96 hours, P 〉0.05）. However, it was worthwhile to note that LHC significantly reduced the severity of illness and the duration of symptoms including fever, cough, sore throat, and fatigue （P〈0.05）. Both study medications were well tolerated. No drug related serious adverse events occurred during the study. Conclusions Compared with Oseltamivir, LHC achieved a similar therapeutic effectiveness reduction of the duration of illness and duration of viral shedding. Therefore, LHC might be an alternative therapeutic measure for influenza A （H1N1） virus infections.

关键词： influenza A （H1N1 ） lianhuaqingwen capsule clinical randomized controlled trial

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