Abstract: Objective To investigate the main chemical constituents of Balanophora involucrata and the mechanism of its anti-inflammatory effect based on network pharmacology and molecular docking technology. Methods Literature reports, Materia Medica, GeneCards and other databases were searched for anti-inflammatory compounds and their targets. String database and Cytoscape 3.7.2 software were used to obtain the protein-protein interaction (PPI) network and the drug-active ingredient-targets network and for GO and KEGG enrichment analyses. Molecular docking was performed using Auto Dock Tools 1.5.6. In an inflammatory RAW264.7 cell model induced by lipopolysaccharide (LPS), the effect of 25, 50, 100, 200 μg/mL Balanophora involucrata extract was tested on the production of inflammatory cytokines and phosphorylation level of PI3K and Akt using ELISA and Western blotting. Results A total of 318 common targets of drugs and diseases were identified, and the core targets were Src, HSP90AA1 and PIK3CA, involving cancer, PI3K/Akt, MAPK and other signaling pathways as shown by KEGG analysis. Molecular docking showed that both the main active constituents of Balanophora involucrata could spontaneously bind to the core targets. In the inflammatory cell model, treatment with Balanophora involucrata extract significantly inhibited the production of IL-1β at the concentrations of 100 and 200 μg/mL, reduced IL-6 and TNF-α expressions at the concentrations of 50, 100, and 200 μg/mL, and lowered phosphorylation levels of PI3K and Akt proteins at the concentrations of 25, 50, 100, and 200 μg/mL (all P<0.05). Conclusions The anti-inflammatory mechanism of Balanophora involucrata involves multiple targets and multiple pathways, and its effect is mediated possibly by reducing IL-1β, IL-6 and TNF-α production and inhibiting phosphorylation levels of PI3K and Akt proteins to suppress the activation of the PI3K/Akt signaling pathway.

Key words: network pharmacology; molecular docking; Balanophora involucrata; anti-inflammation; anti-inflammatory mechanism