Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening.
Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening.
复制标题
基于人体暴露和ACE2生物色谱筛选鉴定中药连花清瘟胶囊潜在抗COVID-19药理成分
DOI：
10.1016/j.apsb.2020.10.002
复制
发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Wu C
中科院分区：
文献类型：
--
作者：
Chen X;Wu Y;Chen C;Gu Y;Zhu C;Wang S;Chen J;Zhang L;Lv L;Zhang G;Yuan Y;Chai Y;Zhu M;Wu C
连花清瘟胶囊是一种中草药产品，已被临床证明对治疗2019冠状病毒病（COVID-19）肺炎有效。然而，人体对LHQW组分的暴露及其药理作用在很大程度上仍然未知。因此，本研究旨在确定LHQW组分的人体暴露及其抗COVID-19药理活性。使用HRMS和非靶向数据挖掘方法的组合进行了重复治疗给药后人血浆和尿液中LHQW组分谱的分析，检测到132种LHQW原型和代谢物组分，它们分别通过胃肠道吸收和通过人体生物转化形成。结合血管紧张素转换酶2（ACE 2）二维生物色谱筛选数据，确定了8个LHQW中暴露于人体且具有潜在ACE 2靶向能力的组分，以进行进一步的药效学评价。结果表明，大黄酸、甘草苷A、甘草苷I、新绿原酸及其异构体对ACE 2有较强的抑制作用。本研究首次从人体暴露的成分出发，为探索六合五味丸胶囊治疗COVID-19患者的疗效分子机制提供了化学和生化证据。它也展示了实用的基于人体解剖学的方法来鉴定中草药的药物活性成分。本研究根据人体暴露的成分，提供了六合彩丸胶囊用于治疗COVID-19患者的化学和生化证据。
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. This study provides chemical and biochemical evidence of LHQW capsule for the treatment of COVID-19 patients based on the components exposed to human.
登录
查看更多内容
DOI：
10.19540/j.cnki.cjcmm.20190210.001
发表时间：
2019-06-01
期刊：
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
影响因子：
--
作者：
Li, Qi;Yin, Jie;Zhu, Xiao-Xin
通讯作者：
Zhu, Xiao-Xin
DOI：
10.1016/j.ijantimicag.2020.105995
发表时间：
2020-06-01
影响因子：
10.8
作者：
Luo, Pan;Liu, Dong;Li, Juan
通讯作者：
Li, Juan
影响因子：
--
作者：
Ding Y;Zeng L;Li R;Chen Q;Zhou B;Chen Q;Cheng PL;Yutao W;Zheng J;Yang Z;Zhang F
通讯作者：
Zhang F
影响因子：
4.1
作者：
Chen, Xiaofei;Cao, Yan;Chai, Yifeng
通讯作者：
Chai, Yifeng
影响因子：
7.4
作者：
Chen, Xiaofei;Cao, Yan;Zhang, Hai;Zhu, Zhenyu;Liu, Min;Liu, Haibin;Ding, Xuan;Hong, Zhanying;Li, Wuhong;Lv, Diya;Wang, Lirong;Zhuo, Xianyi;Zhang, Junping;Xie, Xiang-Qun;Chai, Yifeng
通讯作者：
Chai, Yifeng