Network Pharmacology and Experimental Validation of Qingwen Baidu Decoction Therapeutic Potential in COVID-19-related Lung Injury

Ju Yang; Zhao Zhang; Honghong Liu; Jiawei Wang; Shuying Xie; Pengyan Li; Jianxia Wen; Shizhang Wei; Ruisheng Li; Xiao Ma; Yanling Zhao

doi:10.2174/0113862073236899230919062725

Network Pharmacology and Experimental Validation of Qingwen Baidu Decoction Therapeutic Potential in COVID-19-related Lung Injury

Comb Chem High Throughput Screen. 2023 Nov 10. doi: 10.2174/0113862073236899230919062725. Online ahead of print.

Authors

Ju Yang^{1

2}, Zhao Zhang^{1

2}, Honghong Liu², Jiawei Wang^{1

2}, Shuying Xie², Pengyan Li², Jianxia Wen^{1

2}, Shizhang Wei², Ruisheng Li², Xiao Ma¹, Yanling Zhao²

Affiliations

¹ College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
² Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China.

PMID: 37957903
DOI: 10.2174/0113862073236899230919062725

Abstract

Background and purpose: Coronavirus disease 2019 (COVID-19) is a lifethreatening disease worldwide due to its high infection and serious outcomes resulting from acute lung injury. Qingwen Baidu decoction (QBD), a well-known herbal prescription, has shown significant efficacy in patients with Coronavirus disease 2019. Hence, this study aims to uncover the molecular mechanism of QBD in treating COVID-19-related lung injury.

Methods: Traditional Chinese Medicine Systems Pharmacology database (TCMSP), DrugBanks database, and Chinese Knowledge Infrastructure Project (CNKI) were used to retrieve the active ingredients of QBD. Drug and disease targets were collected using UniProt and Online Mendelian Inheritance in Man databases (OMIM). The core targets of QBD for pneumonia were analyzed by the Protein-Protein Interaction Network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the underlying molecular mechanisms. The analysis of key targets using molecular docking and animal experiments was also validated.

Results: A compound-direct-acting target network mainly containing 171 compounds and 110 corresponding direct targets was constructed. The key targets included STAT3, c-JUN, TNF-α, MAPK3, MAPK1, FOS, PPARG, MAPK8, IFNG, NFκB1, etc. Moreover, 117 signaling pathways mainly involved in cytokine storm, inflammatory response, immune stress, oxidative stress and glucose metabolism were found by KEGG. The molecular docking results showed that the quercetin, alanine, and kaempferol in QBD demonstrated the strongest affinity to STAT3, c- JUN, and TNF-α. Experimental results displayed that QBD could effectively reduce the pathological damage to lung tissue by LPS and significantly alleviate the expression levels of the three key targets, thus playing a potential therapeutic role in COVID-19.

Conclusion: QBD might be a promising therapeutic agent for COVID-19 via ameliorating STAT3-related signals.

Keywords: Acute lung injury; Acute lung injury Network pharmacology; COVID-19; Molecular docking; Network pharmacology; Qingwen Baidu Decoction.