基于网络药理学探讨灵芝抗心力衰竭炎症反应的作用机制OA

Objective To investigate the potential active small molecules and their mechanisms of action of Lingzhi(Ganoderma),a representative Chinese medicinal herb with food-medicine homology,in intervening in the inflammatory response of heart failure.Methods Databases including TCMSP and GEO chip data were integrated to screen candidate active components of Lingzhi(Ganoderma)and differential targets associated with heart failure.The network was constructed using Cytoscape 3.10.4 software,and key targets were identified.Functional enrichment analysis was performed using R language,and molecular docking validation was carried out using CB-Dock2.Results Small-molecule components such as quercetin and genistein exhibited relatively high network connectivity.A total of 71 intersecting targets,including matrix metalloproteinase(MMP)-9 and interleukin(IL)-1β,were mainly enriched in pathways related to the regulation of inflammatory response,IL-17,and Toll-like receptor(TLR)signaling.Among the candidate components,Lingzhi(Ganoderma)characteristic triterpenes such as ganoderic acid F were also identified.Representative flavonoid components exhibited binding free energies≤-5.0 kcal/mol with MMP-9 and IL-1β,and formed non-covalent interactions such as hydrogen bonds and hydrophobic interactions with multiple residues in the binding pocket.Conclusion Within the framework of small-molecule components identifiable from current databases,Lingzhi(Ganoderma)may participate in the regulation of heart failure inflammation by acting on targets such as IL-1β and MMP-9.However,these findings cannot be directly extrapolated to the overall mechanism of action of the whole component system of Lingzhi(Ganoderma).