This study aims to reveal the active ingredients and mechanism of Maimendong decoction (MMDT)in the treatment of radiation-induced lung injury (RILI) based on network pharmacology,molecular docking and experimental verification.Firstly,the MMDT active ingredient targets and the RILI disease targets were screened,and a “drug-ingredient-target” network was constructed.The core targets and relevant signaling pathways were determined through protein-protein interaction network,GO and KEGG enrichment analyses.Then,molecular docking was used to analyze the core ingredients and core targets.Finally,the mechanism of MMDT was verified by cultured A549 cells in vitro and mouse animal model in vivo.There were 261 intersection targets in the treatment of RILI by MMDT,and 63 core intersection targets were selected by network topology analysis degree,including six core intersection targets such as tumor protein P53 (TP53),protein kinase B (AKT),signal transducer and activator of transcription 3 (STAT3),tyrosine-protein kinase (SRC),tumor necrosis factor (TNF),and interleukin-6 (IL-6).KEGG signaling pathway enrichment included TNF,P53,phosphatidylinositol 3-kinase (PI3K)/AKT,etc.signaling pathways.We further obtained six core components,including ophiopogonin D,resveratrol,quercetin,berberine,curcumin,and ursolic acid.Molecular docking was conducted using ophiopogonin D,resveratrol with TP53,AKT,STAT3,SRC,TNF,and IL-6.The in vitro experimental results showed that irradiation of A549 cells could lead to the decrease of cell viability,and secretion of pro-inflammatory cytokines TNF-α,IL-1β,IL-6 and IL-10 increased.Ophiopogonin D and resveratrol improved the irradiation-induced decreased cell viability of A549 cells and inhibited the secretion of intracellular pro-inflammatory factors.At the same time,ophiopogonin D and resveratrol could play an anti-inflammatory role by regulating the expression of TP53,SRC,STAT3,IL-6 transcription and protein phosphorylation in A549 cell,so as to effectively improve the effect of RILI.The in vivo experiments showed that MMDT could improve irradiation-induced inflammatory factor infiltrating lung tissue after irradiation in mice,and its mechanism which the core components of ophiopogonin D and resveratrol regulate the expression of TP53,p-SRC and p-STAT3 in vivo to play an anti-inflammatory role,thus achieving the effect of improving RILI.This study revealed the therapeutic effect of MMDT on RILI may be achieved through the effect of ophiopogonin D and resveratrol on the TP53/SRC/STAT3 signal axis.

"> Maimengdong decoction, radiation-induced lung injury, network pharmacology, ophiopogonin D, resveratrol, TP53/SRC/STAT3 signal axis