Mechanisms of Xiangxue decoction in treating COVID-19 via HPLC‒Q-TOF‒MS/MS, network pharmacology, molecular docking and molecular dynamics simulation

To predict the active components of Xiangxue Decoction (XXD), and explore its mechanism in treatment of COVID-19. The chemical compositions of compounds were identified using HPLC‒Q-TOF‒MS/MS technology. Active components were screened using UNIFI, and potential targets were retrieved from TCMSP, GeneCards. The STRING database was used to construct PPI networks. Enrichment analysis was conducted using Metascape. Molecular docking and Molecular dynamics simulations were further used to evaluate the interactions between the active components and potential targets. 162 drug targets, 1458 disease targets and 64 intersection targets were identified. Quercetin, kaempferol, luteolin, nobiletin and β-carotene were identified as the key components. The core targets included TNF, AKT1, IL-6, IL1B, HIF1A, STAT3 and EGFR. GO and KEGG analyses revealed the primary signaling pathways, including the JAK-STAT, MAPK, PI3K / Akt, and NF-kappa B. Molecular dynamics simulations confirmed β-carotene-IL-6, β-carotene-EGFR and β-carotene-TNF revealed preferable stability. Finally, HPLC‒Q-TOF‒MS/MS analysis detected 158 low-abundance and 73 high-abundance compounds in the XXD extract. The mechanism of XXD is complex and may be related to its signaling pathway. These results may support the use of XXD for the treatment of COVID-19.