Abstract
IntroductionThe overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19. Astragaloside IV is considered as an anti-inflammatory and antioxidant agent. This study aimed at undertaking a network pharmacology approach and bioinformatics analysis to uncover the pharmacological mechanisms of Astragaloside IV on COVID-19.MethodsPotential targets of Astragaloside IV were screened from public databases. Differentially expressed genes (DEGs) in SARS-CoV-2 were screened using bioinformatics analysis on the Gene Expression Omnibus (GEO) datasets GSE147507. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. The overlapping genes, GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs were confirmed, and the location of overlapping targets in the key pathways was queried using KEGG Mapper.ResultsA total of 425 potential targets of Astragaloside IV were screened. Besides, a total of 546 DEGs were identified between SARS-CoV-2 infected samples and control samples, including 380 up-regulated and 166 down-regulated genes. There was a significant overlap in GO terms and KEGG pathways between Astragaloside IV targets and SARS-CoV-2 DEGs. The shared genes included MMP13, NLRP3, TRIM21, GBP1, ADORA2A, PTAFR, TNF, MLNR, IL1B, NFKBIA, ADRB2, and IL6.ConclusionsThis study is the first to propose Astragaloside IV as a new drug candidate for alleviating hyper-inflammation in COVID-19 patients. Besides, the key targets and pathways may reveal the main pharmacological mechanism of Astragaloside IV in the treatment of COVID-19.
Highlights
The overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19
The molecular structure of Astragaloside IV was download from PubChem (Figure 2), and PubChem CID of Astragaloside IV is 13943297
A total of five corresponding potential targets of Astragaloside IV were identified from TargetNet.19, while the corresponding potential targets of Astragaloside IV were identified from CTD
Summary
The overproduction of cytokines and chemokines caused by excessive and uncontrolled inflammation contributes to the development of COVID-19. This study aimed at undertaking a network pharmacology approach and bioinformatics analysis to uncover the pharmacological mechanisms of Astragaloside IV on COVID-19. Clinical studies have revealed that COVID-19 patients admitted to intensive care have increased expression of inflammatory cytokines (IL-6, IL-10, IL-2, and IFN-g). Other studies confirm that a large number of patients with severe COVID-19 are likely to suffer a cytokine storm syndrome (Huang et al, 2020; Shen et al, 2020; Ye et al, 2020). ARDS and cytokine storms occur very often in patients with COVID-19 since excess production of pro-inflammatory cytokines results in ARDS aggravation (Howell and Davis, 2018). There a need to search for therapies to reduce hyper-inflammation and improve prognosis in severe COVID-19 patients
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