Investigating the potential anti-inflammatory mechanism of benzophenone compounds from the leaves of Aquilaria sinensis (Lour.) Gilg based on network pharmacology and molecular docking strategies

Abstract

Background

Aquilaria sinensis (Lour.) Gilg (ASG) has been used as traditional medicine for centuries. However, the active ingredients from leaves and their anti-inflammatory mechanism are rarely reported. The network pharmacology and molecular docking strategies were applied to explore the potential mechanisms of Benzophenone compounds from the leaves of ASG (BLASG) against inflammation.

Methods

BLASG-related targets were obtained from the SwissTargetPrediction and PharmMapper databases. Inflammation-associated targets were retrieved from GeneGards, DisGeNET, and CTD databases. Cytoscape software was used to draw a network diagram of BLASG and its corresponding targets. DAVID database was applied for enrichment analyses. A protein-protein interaction (PPI) network was constructed to identify the hub targets of BLASG. Molecular docking analyses were performed by AutoDockTools 1.5.6. Moreover, we used ELISA and qRT-PCR assays to validate the anti-inflammatory effects of BLASG by cell experiments.

Results

Four BLASG were extracted from ASG, and corresponding 225 potential targets were identified. PPI network analysis indicated that SRC, PIK3R1, AKT1, and other targets were the core therapeutic targets. Enrichment analyses revealed that the effects of BLASG are regulated by targets associated with apoptosis and inflammation-related pathways. In addition, molecular docking revealed that BLASG combined well with PI3K and AKT1. Furthermore, BLASG significantly decreased the inflammatory cytokines levels and down-regulated PIK3R1 and AKT1 gene expression in RAW264.7 cells.

Conclusion

Our study predicted the potential targets and pathways of BLASG against inflammation, which offered a promising strategy to reveal the therapeutic mechanism of natural active components in the treatment of diseases.

Keywords:

• Aquilaria sinensis
• network pharmacology
• molecular docking
• inflammation

Author contributions

Weihua Zhang wrote the main manuscript text. Feng Zhao, Yuan Zhi, Xiayin Wang, Shuai Yang, Dan Sun, and Nan Lv prepared figures and performed bioinformatics analysis. Xiaojing Wu edited the article. All authors reviewed the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data can be obtained from the website we provide, and are available from the corresponding author upon request.

Additional information

Funding

This work was sponsored by the study on the mechanism of CAG apoptosis mediated by the PI3K-Akt signaling pathway through the regulation of circRNA by BLASG compounds.