Network pharmacology-based prediction of the potential mechanism of cinnamaldehyde in regulating host immune responses to PRRSV

The potential targets and signaling pathways involved in cinnamaldehyde （CA）‐mediated regulation of host immune responses against porcine reproductive and respiratory syndrome virus （PRRSV） were predicted based on the integration of multiple databases and network pharmacological analyses， providing a theoretical basis for subsequent in vivo validation experiments. First， the potential targets of CA were obtained by searching the PubChem， PharmMapper and TCMSP databases， and the key targets were screened by intersecting them with PRRSV‐associated host genes retrieved from the CTD database. Subsequently， a protein‐protein interaction （PPI） network was constructed using the STRING database， and core targets were identified through topological analysis. Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed on the key targets using the DAVID database. Finally， a "compound‐target‐pathway" network was constructed using Cytoscape to systematically elucidate the underlying associations. A total of 134 potential targets of CA were obtained， and 47 key targets were identified after intersection with PRRSV‑related genes. Topological analysis of the PPI network identified 13 core targets， including TLR4， RELA （p65）， NFKBIA （IκBα）， NFE2L2 （NRF2）， HMOX1， JAK1 and JAK2. Functional enrichment analysis yielded 154 enriched terms， among which NF-κB binding activity exhibited the highest enrichment significance in the molecular function category （-log₁₀P>5）. KEGG pathway enrichment analysis identified 60 significantly enriched pathways， which were mainly associated with immune-inflammatory signaling pathways， including Toll-like receptor， NF‑κB， and NOD-like receptor pathways. In conclusion， CA was suggested to participate in the host immune response against PRRSV infection by regulating immune-inflammatory signaling pathways， such as the TLR4/NF‑κB and NOD-like receptor pathways. These findings provided a more comprehensive theoretical perspective for understanding the multi‑target antiviral mechanisms of CA and established a scientific foundation for further in vivo validation of its anti-PRRSV effects.