Potential Mechanisms of Perillae folium Against COVID-19: A Network Pharmacology Approach

In China, Perillae folium is widely used to treat colds, especially in the early stages of cold; the effect of taking P. folium is readily noticeable at that time. The active compounds and targets of P. folium were screened from Traditional Chinese Medicine Systems Pharmacology, Chinese Pharmacopoeia, and UniProt. Targets related to the initiation and progression of 2019 Coronavirus Disease (COVID-19) were retrieved from Online Mendelian Inheritance in Man and GeneCards. The potential therapeutic targets of P. folium on COVID-19 were the cross targets between them. Enrichment analysis of Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted by using the Database for Annotation, Visualization and Integrated Discovery website. Molecular docking between key compounds and core targets was performed with AutoDock. The effects of P. folium extract and rosmarinic acid on inflammatory cytokines were tested by a cellular inflammatory model. The "Perillae folium-compound-target-COVID-19" network contained 11 kinds of compounds and 33 matching targets. There were 261 items in the GO functions (P < .05) and 67 items linked to the KEGG signaling pathways (P < .05). Luteolin and rosmarinic acid were key compounds of P. folium. Their docking with the core targets mitogen-activated protein kinase 1 (MAPK1) and chemokine (C-C motif) ligand 2 (CCL2), respectively, showed that they had good affinity with each other. Cell experiments demonstrated that P. folium extract had inhibitory effects on interleukin-6 and tumor necrosis factor (TNF)-α in cells, and was better than rosmarinic acid. Luteolin, rosmarinic acid, and other individual active compounds in P. folium, which may participate in PI3K-Akt, TNF, Jak-STAT, COVID-19, and other multisignaling pathways through multiple targets such as MAPK1 and CCL2, and play a therapeutic role in COVID-19.