Investigation of meranzin hydrate's immunoenhancing effects and mechanisms based on zebrafish model organism and network pharmacology
Objective To investigate the immunoenhancing effects and mechanisms of action of meranzin hydrate(MH),an active component of Aurantii Fructus,based on the model organism zebrafish in combination with network pharmacology.Methods Two types of immunocompromised zebrafish models were established:One using rapamycin to reduce the number of neutrophils in the tail,and another using vinorelbine to diminish the fluorescence intensity of macrophages in tail vein vessels.The neutrophil count in the tail and the fluorescence intensity of macrophages in tail vein vessels were measured in each treatment group of MH(10,20,50、100,and 200 pg·mL-1),and the growth rate of neutrophils(％)and the improvement rate of macrophages(％)were calculated.The mechanism by which MH enhances immune function was predicted using network pharmacology,with target screening for MH conducted using PharmMapper and the TCMSP database.Immune-related targets were retrieved from the Gene Cards and OMIM databases.Intersection of these target sets was analyzed for protein interactions in the String Database,followed by GO and KEGG analyses.A PPI network of MH's immunomodulatory action was constructed in Cytoscape 3.9.1,with key targets identified based on the median degree value of nodes.Results Compared to the model group,MH significantly increased both the neutrophil count(P＜0.01,0.001)in the tail and the fluorescence intensity(P＜0.05)of macrophages in tail vein vessels,demonstrating its dose-dependent protective effects against immune suppression induced by rapamycin and camptothecin.The immunoenhancing mechanism of MH may be associated with key targets such as AKT1,EGFR,SRC,MMP9,ESRI,and signaling pathways including PI3K-Akt,Rap1,and AGE-RAGE.Conclusion MH enhances immune function,potentially through the regulation of PI3K-Akt,Rap1,and AGE-RAGE signaling pathways.
NETL
NSTL
万方数据
