Prediction of the Active Components and Mechanism of Forsythia suspensa Leaf against Respiratory Syncytial Virus Based on Network Pharmacology

OBJECTIVE: Forsythia suspensa leaf (FSL) has been used as a health tea in China for centuries. Previous experiments have proved that FSL extract has a good effect on the antirespiratory syncytial virus (RSV) in vitro, but its exact mechanism is not clear. Therefore, this study aims to determine the active components and targets of FSL and further explore its anti-RSV mechanism. METHODS: UPLC-Q-Exactive-MS was used to analyze the main chemical components of FSL. The compound disease target network, PPI, GO, and KEGG were used to obtain key targets and potential ways. Then, the molecular docking was verified by Schrödinger Maestro software. Next, the cell model of RSV infection was established, and the inhibitory effect of each drug on RSV was detected. Finally, western blotting was used to detect the effect of the active components of FSL on the expression of PI3K/AKT signaling pathway-related protein. RESULTS: UPLC-Q-Exactive-MS analysis showed that there were 67 main chemical constituents in FSL, while network pharmacological analysis showed that there were 169 anti-RSV targets of the active components in FSL, involving 177 signal pathways, among which PI3K/AKT signal pathway played an important role in the anti-RSV process of FSL. The results of molecular docking showed that cryptochlorogenic acid, phillyrin, phillygenin, rutin, and rosmarinic acid had higher binding activities to TP53, STAT3, MAPK1, AKT1, and MAPK3, respectively. In vitro experiments showed that phillyrin and rosmarinic acid could effectively improve the survival rate of RSV-infected cells, increase the expression level of PI3K, and decrease the expression level of AKT. CONCLUSION: The active ingredients of FSL, phillyrin, and rosmarinic acid can play an anti-RSV role by inhibiting PI3K/AKT signaling pathway. This study provides reliable theoretical and experimental support for the anti-RSV treatment of FSL.