Li Zhang^{1, 2}, Yuqing Wang¹, Qili Lu¹, Fengying Ye¹, Qing Zhang^{3, 4}, Feifei Wang^{3, 4}, Shuyao Zhang^1,, Feng Wang^{3, 4,}

Benzoinum is a resin derived from Styrax tonkinensis bark that has long been used in clinical settings as a traditional Chinese medicine with cardioprotective properties. The mechanistic basis for these pharmacological properties, however, remains to be demarcated. We used a network pharmacology approach to characterise the mechanism of action that benzoinum used to treat AS. The PharmMapper database was used to find potential benzoin target proteins, and the TCMSP, CTD, TTD, GAD, drug Bank, and pharmGkb databases were used to identify AS-related target genes. Following assessments of pathway enrichment, the functional roles of these genes were discovered, allowing the creation of compound-target and target-pathway networks. HUVEC cells were then used to validate these predicted benzoinum-related mechanisms of action, revealing that an active derivative of this resin was able to modulate signaling activity in TNF-α-exposed HUVECs by regulating the caspase-9 and NF-κB signaling pathways. Overall, our predictive network pharmacology analyses and supporting data highlighted the potential mechanisms whereby benzoinum may exert cardiovascular activity in the context of AS.

network pharmacology, atherosclerosis, cell apoptosis, inflammatory