Deciphering suppressive effects of Lianhua Qingwen Capsule on COVID-19 and synergistic effects of its major botanical drug pairs.

The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, ß-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.

New insights for infection mechanism and potential targets of COVID-19: Three Chinese patent medicines and three Chinese medicine formulas as promising therapeutic approaches.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high pathogenicity and infectiousness has become a sudden and lethal pandemic worldwide. Currently, there is no accepted specific drug for COVID-19 treatment. Therefore, it is extremely urgent to clarify the pathogenic mechanism and develop effective therapies for patients with COVID-19. According to several reliable reports from China, traditional Chinese medicine (TCM), especially for three Chinese patent medicines and three Chinese medicine formulas, has been demonstrated to effectively alleviate the symptoms of COVID-19 either used alone or in combination with Western medicines. In this review, we systematically summarized and analyzed the pathogenesis of COVID-19, the detailed clinical practice, active ingredients investigation, network pharmacology prediction and underlying mechanism verification of three Chinese patent medicines and three Chinese medicine formulas in the COVID-19 combat. Additionally, we summarized some promising and high-frequency drugs of these prescriptions and discussed their regulatory mechanism, which provides guidance for the development of new drugs against COVID-19. Collectively, by addressing critical challenges, for example, unclear targets and complicated active ingredients of these medicines and formulas, we believe that TCM will represent promising and efficient strategies for curing COVID-19 and related pandemics.

Qualitative analysis of chemical components in Lianhua Qingwen capsule by HPLC-Q Exactive-Orbitrap-MS coupled with GC-MS.

The Lianhua Qingwen (LHQW) capsule is a popular traditional Chinese medicine for the treatment of viral respiratory diseases. In particular, it has been recently prescribed to treat infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, due to its complex composition, little attention has been directed toward the analysis of chemical constituents present in the LHQW capsule. This study presents a reliable and comprehensive approach to characterizing the chemical constituents present in LHQW by high-performance liquid chromatography-Q Exactive-Orbitrap mass spectrometry (HPLC-Q Exactive-Orbitrap-MS) coupled with gas chromatography-mass spectrometry (GC-MS). An automated library alignment method with a high mass accuracy (within 5 ppm) was used for the rapid identification of compounds. A total of 104 compounds, consisting of alkaloids, flavonoids, phenols, phenolic acids, phenylpropanoids, quinones, terpenoids, and other phytochemicals, were successfully characterized. In addition, the fragmentation pathways and characteristic fragments of some representative compounds were elucidated. GC-MS analysis was conducted to characterize the volatile compounds present in LHQW. In total, 17 compounds were putatively characterized by comparing the acquired data with that from the NIST library. The major constituent was menthol, and all the other compounds were terpenoids. This is the first comprehensive report on the identification of the major chemical constituents present in the LHQW capsule by HPLC-Q Exactive-Orbitrap-MS, coupled with GC-MS, and the results of this study can be used for the quality control and standardization of LHQW capsules.

The mechanisms and clinical application of Traditional Chinese Medicine Lianhua-Qingwen capsule.

Lianhua-Qingwen capsule (LQC) is a commonly used Traditional Chinese Medicine (TCM) in China and has 11 herb components. The main active ingredient can target specific molecules and perform many clinic treatment roles. LQC has been authorized by National Medical Products Administration (NMPA) of China to treat severe acute respiratory syndrome (SARS) in 2002-2003, type A influenza virus HIN1 pandemic in 2009, H7N9, H3N2 and coronavirus disease-19 (COVID19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in 2020. It is also widely used to treat common cold with wind-heat syndrome, chronic rhinosinusitis (CRS), amygdalitis and chronic obstructive pulmonary disease. This article summarizes the advanced research progress of LQC in clinical application, mechanisms and provides new clues in the clinical application of LQC.

[Mechanism and material basis of Lianhua Qingwen capsule for improving clinical cure rate of COVID-19: a study based on network pharmacology and molecular docking technology].

OBJECTIVE: To explore the potential targets, signal pathways and biological functions that mediate the effect of Lianhua Qingwen capsule in improving clinical cure rate of COVID-19 in light of network pharmacology and molecular docking technology. METHODS: TCMSP, Target, Prediction, CooLGeN, GeneCards, DAVID and other databases were searched for the active components and their target proteins from 13 herbs including Forsythia, Honeysuckle and roasted Ephedra used in Lianhua Qingwen capsule. The common target proteins, signal pathways and biological functions shared by these components and the clinical manifestations of COVID-19 (fever, cough, and fatigue) were identified to construct the network consisting of the component drugs in Lianhua Qingwen capsule, the active ingredients of, their targets of action, and the biological functions involved using Gephi software. RESULTS: A total 160 active components including MOL000522, and MOL003283, MOL003365, MOL003006, MOL003014 in 13 component drugs in Lianhua Qingwen capsule produced therapeutic effects against COVID-19 through 57 target proteins including MAPK1, IL6, HSP90AA1, TNF, and CCL2, involving 35 signaling pathways including NOD-like receptor signaling pathway and Toll-like receptor signaling pathway. The results of molecular docking showed that 83 chemical components had total scores no less than 5.0 for docking with 12 target proteins (including MAPK1, IL6, and HSP90AA1) with high binding activities to form stable conformations. The binding of MOL000522, MOL004989, and MOL003330 with MAPK1; MOL001495 and MOL001494 with NLRP3; MOL004908, MOL004863 and MOL004806 with HSP90AA1; MOL001749 with TLR9; and MOL001495 with AKT1 all had total scores exceeding 9.0. CONCLUSIONS: Lianhua Qingwen capsule contains multiple effective ingredients to improve clinical cure rate of COVID-19, and its therapeutic effect is mediated by multiple protein targets, signal pathways and biological functions.

Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID-19.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide. Lianhua Qingwen capsule (LQC) has shown therapeutic effects in patients with COVID-19. This study is aimed to discover its molecular mechanism and provide potential drug targets. MATERIALS AND METHODS: An LQC target and COVID-19-related gene set was established using the Traditional Chinese Medicine Systems Pharmacology database and seven disease-gene databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network were performed to discover the potential mechanism. Molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. RESULTS: A gene set of 65 genes was generated. We then constructed a compound-target network that contained 234 nodes of active compounds and 916 edges of compound-target pairs. The GO and KEGG indicated that LQC can act by regulating immune response, apoptosis and virus infection. PPI network and subnetworks identified nine hub genes. The molecular docking was conducted on the most significant gene Akt1, which is involved in lung injury, lung fibrogenesis and virus infection. Six active compounds of LQC can enter the active pocket of Akt1, namely beta-carotene, kaempferol, luteolin, naringenin, quercetin and wogonin, thereby exerting potential therapeutic effects in COVID-19. CONCLUSIONS: The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism of LQC. Akt1 is a promising drug target to reduce tissue damage and help eliminate virus infection.