Abstract： Objective To predict the mechanism of honeysuckle for IgA nephropathy(IgAN)by network pharmacology,and to verify the results by in vitro experiments.Methods The main active components of honeysuckle were obtained through TCMSP platform.The related targets of IgAN were retrieved by GeneCards and OMIM database,and mapped to the potential targets of honeysuckle.The targets of IgAN and honeysuckle were overlapped,and the KEGG pathway enrichment analysis was performed by constructing drug-component-disease-target network diagram.Finally,an cell model of IgAN was constructed by co-culturing human glomerular endothelial cells(HRGECs)and human mesangial cells(HMCs)stimulated with recombinant human IgA.Different concentrations of luteolin were given to verify the network pharmacology results.Results Network pharmacology analysis showed that PI3K-AKT signaling pathway might be a potential target of honeysuckle for IgAN.The topological analysis of network diagram showed that the active component luteolin was most related to PI3K-AKT signaling pathway.In vitro experiments showed that luteolin inhibited the proliferation of HMCs and reduced the secretion of inflammatory factor IL-6,thus enhancing the expression of adhesion molecules in HRGECs,improving the junction between cells and reducing the permeability of HRGECs monolayers.The expression of PI3K-AKT signaling pathway-related proteins in HMCs was detected,and luteolin inhibited the phosphorylation of PI3K and AKT in cells.Conclusion Luteolin inhibits the proliferation of HMCs and IL-6 secretion by inhibiting PI3K-AKT signaling pathway to improve glomerular filtration barriers in IgAN.