Network pharmacological analysis and mechanism prediction of Xiaochaihu Decoction in treatment of COVID-19 with syndrome of pathogenic heat lingering in lung and obstructive cardinalate / 中草药

ABSTRACT

Objective: To study the efficacy network and potential mechanism of Xiaochaihu Decoction (XCHD) in the treatment of coronavirus disease 2019 (COVID-19) with syndrome of pathogenic heat lingering in the lung and obstructive cardinalat, and analyze the active ingredients of XCHD with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficacy. Methods: The correspondence between COVID-19 and XCHD was analyzed by literature consulting. Based on network pharmacology, Cytoscape 3.6.0 and other software were then used to construct XCHD efficacy network of “Chinese medicine prescription-active ingredient-key target” for pneumonia and immune regulation, in order to confirm anti-SARS-CoV-2 active ingredients in the prescription. Some softwares were used to analyze XCHD for COVID-19 treatment in multiple aspects. Results: A total of 48 active ingredients with potential anti-SARS-CoV-2 effect in herbs were collected; 140 active ingredients in XCHD for pneumonia treatment and immune regulation were analyzed, of which 12 ingredients had direct anti-SARS-CoV-2 activity including baicalein, formononetin, quercetin, etc. The active ingredients in XCHD exerted efficacy for pneumonia treatment and immunoregulation through 95 key targets such as IL-6, NOS2, and ESR1, involving multiple pathways such as the TNF signaling pathway, IL-17 signaling pathway, and influenza A. Analysis of gene co-expression and PPI interaction analysis found that ACE2 only co-expressed with NOS2 in the above targets, and also interacted with only five targets in the PPI interaction network. It is speculated that the ACE2 target only plays an important role when SARS-CoV-2 invaded the human body, and had little effect in the treatment of pneumonia after viral infection. Conclusion: The active ingredients in XCHD play a role in treating COVID-19 by inhibiting SARS-CoV-2 activity, blocking the SARS-CoV-2 invasion pathway, inhibiting cytokine storm, and regulating immunity. It is worth noting that drugs designed for the ACE2 target can block virus invasion, but may not be effective for diseases such as alveolar inflammation, Therefore, this study also provides a multi-target and multi-directional space for XCHD for early COVID-19 treatment. In addition, when XCHD is used in the early treatment of COVID-19, we should pay attention to the precise use of drugs based on syndrome accurate identification, one is to avoid adverse reactions, the other is to avoid cytokine damage caused by re-crown disease.