龙脷叶75%乙醇提取物止咳作用及网络药理学研究OACHSSCD

Objective:To investigate the antitussive effects and mechanisms of the 75%ethanol extract of Sauropus spatulifolius Beille leave.Methods:A cough model was established by capsaicin aerosol induction.The rats were randomly assigned into the blank group,model group,pentoxyverine citrate group,and high-,medium-,and low-dose groups of the 75%ethanol extract of S.spatulifolius leaves,with 6 rats in each group.The antitussive efficacy of the 75%ethanol extract of S.spatulifolius leaves was eval-uated by determining the cough inhibition rate in rats.Histopathological changes in rat lung tissues were observed using hematoxy-lin-eosin(HE)staining,and the levels of calcitonin gene-related peptide(CGRP)and neurokinin A(NKA)in lung tissues and ser-um were measured.Network pharmacology and molecular docking analyses were used to evaluate the mechanisms underlying the an-titussive effects of the 75%ethanol extract of S.spatulifolius leaves.Results:During the pharmacodynamic experiments,all rats in each group exhibited normal food and water intake,and no deaths occurred.Except for the model group,all other groups showed re-duced capsaicin-induced cough frequency,indicating good antitussive effects.Compared with the model group,the high-and medi-um-dose groups showed statistically significant differences(P<0.05),with increased organ indices,and lung consolidation was markedly improved in all administration groups.The concentrations of CGRP in lung tissues and serum of the pentoxyverine citrate group and medium-dose group were significantly lower than those in the model group,with statistically significant differences(P<0.05).Network pharmacology analysis identified 24 active compounds,399 key compound-related targets,key intersecting targets including signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),and heat shock protein 90 alpha family class A member 1(HSP90AA1),as well as 172 related Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways.Molecular docking results showed that SRC had relatively high binding activity with apigenin,while epidermal growth factor receptor(EGFR)exhibited relatively high binding activity with 7-hydroxycoumarin,emodin,apigenin,and kaempferol.Conclusion:The 75%ethanol extract of S.spatulifolius leaves exhibits antitussive effects in capsaicin-induced cough rats and may exert its antitussive activity by reducing CGRP expression levels in lung tissues and serum.The underlying mecha-nisms may also involve the regulation of targets such as STAT3 and SRC by multiple components,including apigenin,EGFR-related compounds,7-hydroxycoumarin,emodin,and kaempferol.