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

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.

Screening and evaluation of anti-SARS-CoV-2 components from Ephedra sinica by ACE2/CMC-HPLC-IT-TOF-MS approach

“…In the present study, the ACE2/CMC model was combined with HPLC-IT-TOF-MS to develop a two-dimensional analysis method for TCMs screening, making the screening work more efficient, fast, and convenient. Chen et al [ 40 ] also synthesized a novel ACE2 biochromatographic stationary phase for the screening of potential ACE2-targeted components from extract of Lianhuaqingwen capsule. Results confirmed the suitability and efficiency of ACE2/CMC model and its coupled system.…”

Traditional Chinese medicine Lianhua Qingwen for treating COVID-19

“…LHQW could reduce patient mortality, improve clinical symptoms (such as fever, cough, fatigue) for COVID-19. [ 11 ] The results network pharmacology showed that LHQW prescription acted on coronavirus through multiple components, multiple targets, and multiple pathways. The major components not only have good binding ability with ACE2, but also effectively bind to the contact surface of ACE2 and the spinous process complex, thus playing a potential therapeutic role in COVID-19.…”

Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts

“…(B) Raw materials of Lianhuaqingwen capsules. (C) Molecular docking of representative components (prunasin, rhein, forsythoside I, and neochlorogenic acid) with ACE2 (image reproduced with permission from Chen et al, 2020c ). …”

“…Results demonstrated that certain representative components exhibited high inhibitory effects on ACE2, including prunasin (affects the binding interface of ACE2 and S protein), rhein (the best binding interface of ACE2), forsythoside I (the binding interface of ACE2), and neochlorogenic acid (the binding interface of peptidase and S protein) ( Fig. 8 C) ( Chen et al, 2020c ). As a large formulation, LHQW may possess complex mechanisms of action; however, these are currently undefined and require additional research.…”