Network Pharmacology Analysis to Identify Phytochemicals in Traditional Chinese Medicines That May Regulate ACE2 for the Treatment of COVID-19.

Min Fan,Haiming Cui,Feng Wu,Wenhao Niu,Jianming Guo,Wenyue Cao,Chun Liang,Zonggui Wu,Yuchieh Chao

doi:10.1155/2020/7493281

Abstract

“Three formulas and three medicines,” which include Jinhua Qinggan granule, Lianhua Qingwen capsule/granule, Xuebijing injection, Qingfei Paidu decoction, HuaShiBaiDu formula, and XuanFeiBaiDu granule, have been proven to be effective in curbing coronavirus disease 2019 (COVID-19), according to the State Administration of Traditional Chinese Medicine. The aims of this study were to identify the active components of “Three formulas and three medicines” that can be used to treat COVID-19, determine their mechanism of action via angiotensin-converting enzyme 2 (ACE2) by integrating network pharmacological approaches, and confirm the most effective components for COVID-19 treatment or prevention. We investigated all the compounds present in the aforementioned herbal ingredients. Compounds that could downregulate the transcription factors (TFs) of ACE2 and upregulate miRNAs of ACE2 were screened via a network pharmacology approach. Hepatocyte nuclear factor 4 alpha (HNF4A), peroxisome proliferator-activated receptor gamma (PPARG), hsa-miR-2113, and hsa-miR-421 were found to regulate ACE2. Several compounds, such as quercetin, decreased ACE2 expression by regulating the aforementioned TFs or miRNAs. After comparison with the compounds present in Glycyrrhiza Radix et Rhizoma, quercetin, glabridin, and gallic acid present in the herbal formulas and medicines were found to alter ACE2 expression. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to search for possible molecular mechanisms of these compounds. In conclusion, traditional Chinese medicine (TCM) plays a pivotal role in the prevention and treatment of COVID-19. Quercetin, glabridin, and gallic acid, the active components of recommended TCM formulas and medicines, can inhibit COVID-19 by downregulating ACE2.

Highlights

Wenhao Niu,1 Feng Wu,2 Haiming Cui,2 Wenyue Cao,3 YuChieh Chao,4 Zonggui Wu,2 Min Fan,2 and Chun Liang 1
Seven versions of the diagnosis and treatment guidelines for COVID-19 have been published by the National Health Commission of China, and various formulas and three medicines have been proven to be effective [4, 9,10,11]. e State Administration of Traditional Chinese Medicine has proven that the “ ree formulas and three medicines,” which include Jinhua Qinggan granule, Lianhua Qingwen capsule/granule, Xuebijing injection, lung cleansing and detoxifying decoction, HuaShiBaiDu formula, and XuanFeiBaiDu granule, are effective against COVID-19
E angiotensin-converting enzyme 2 (ACE2) can bind to the receptor-binding domain (RBD) of spike glycoprotein, which is responsible for the entry of coronaviruses into the host cells [5, 16]. erefore, ACE2 can be regarded as an important intervention target for COVID-19 [17]. erefore, this study focused on active components of traditional Chinese medicine (TCM) on ACE2 and aimed to determine the efficacy of “ ree formulas and three medicines” in the treatment of COVID-19 via network pharmacology

Summary

Introduction

Hepatocyte nuclear factor 4 alpha (HNF4A), peroxisome proliferator-activated receptor gamma (PPARG), hsa-miR-2113, and hsa-miR-421 were found to regulate ACE2 Several compounds, such as quercetin, decreased ACE2 expression by regulating the aforementioned TFs or miRNAs. After comparison with the compounds present in Glycyrrhiza Radix et Rhizoma, quercetin, glabridin, and gallic acid present in the herbal formulas and medicines were found to alter ACE2 expression. Among 91.5% of patients treated with TCM and western medicine, the cure rates were above 90%, according to the National Health Commission report [7, 8]. E State Administration of Traditional Chinese Medicine has proven that the “ ree formulas and three medicines,” which include Jinhua Qinggan granule, Lianhua Qingwen capsule/granule, Xuebijing injection, lung cleansing and detoxifying decoction, HuaShiBaiDu formula, and XuanFeiBaiDu granule, are effective against COVID-19. A recent systematic review indicated that TCM can be used as an alternative approach for preventing COVID-19 in vulnerable populations, based on previous reports on TCM use for SARS and H1NI influenza prevention [14, 15]

Methods

Results

Conclusion