Combination of Network Pharmacology and In Vitro Experiments on LPSinduced A549 Cells to Explore the Molecular Mechanisms of Huanglian Jiedu Decoction Treating Pneumonia

Abstract

Objective: Huanglian Jiedu decoction (HLJDD) was shown to exert therapeutic effect on pneumonia for a long time in China. However, its pharmacological mechanism remains to be elucidated. Methods: The active compounds and target proteins of HLJDD were screened from TCMSP and the targets of pneumonia were obtained from GeneCards. GO and KEGG enrichment were applied in this study. Networks were established by Cytoscape with R-Bioconductor. The affinity between components and targets were detected by molecular docking. Finally, active ingredients and targets were selected to be verified in an inflammatory model established in LPS-induced A549 cells. CCK8 proliferation assay and western blot were performed to test the relative indicators. Results: 102 bioactive components and 205 targets from 4 herbs in HLJDD were collected. 68 potential therapeutic targets and 55 corresponding compounds were screened to establish the networks. 4 active compounds (quercetin, wogonin, kaempferol and baicalein) and 5 hub genes (IL6, AKT1, CXCL8, CCL2 and IL1B) were then selected to make molecular docking. The results indicated that quercetin and wogonin had better affinity with CXCL8, CCL2 or IL1B. In vitro experiments revealed that both quercetin and wogonin could decrease the proliferation inhibiting and apoptosis of A549 cells injured by LPS. The expression CXCL8, CCL2 or IL1B were down-regulated after quercetin or wogonin treating, compared with LPS-induced A549 cells (P < 0.01). Conclusion: The current study suggested that the mechanism of HLJDD treating pneumonia might be inhibiting the apoptosis through targeting the inflammatory factors mainly by quercetin and wogonin.