Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening
- 药学院－已发表论文 
【Abstract】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 2D 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.
Description药学院吴彩胜副教授联合海军军医大学柴逸峰教授团队在连花清瘟胶囊防治新冠肺炎的药理活性成分和机制研究方面取得新进展，这项研究基于HRMS和智能非靶向数据挖掘技术，全面分析了对多次给药后人血浆和尿液中的连花清瘟胶囊成分，合成了全新的ACE2生物色谱固定相，筛选出连花清瘟胶囊提取物和人尿液样品潜在的ACE2靶向成分。这项研究是连花清瘟胶囊的人体暴露信息的首次报道，为其在抗COVID-19的药理活性成分和作用机制研究提供了化学和药理学理论依据。本研究证明基于人体暴露的研究策略可用于高效的发掘中草药中的药效活性物质。The authors would like to thank Prof. Chuan Li in Shanghai Institute of Materia Medica, Chinese Academy of Sciences (Shanghai, China) to provide biological samples and technical guidance. This research was 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; “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).
CitationActa Pharmaceutica Sinica B,2020:doi.org/10.1016/j.apsb.2020.10.002