Study On The Mechanism Of Platycodon Grandiflorus Decoction In The Treatment Of Acute Lung Injury Based On UPLC-Q-TOF-MS/MS And Network Pharmacology

Purpose: Acute lung injury(ALI)is a type of diffuse lung inflammation caused by various internal and external stimuli.PGD has been demonstrated to exert a protective effect against ALI.However,its exact mechanism of action is unknown.To investigate the mechanism of action of PGD against ALI by network pharmacology and UPLC-Q-TOF-MS/MS.Methods: A mouse model of lipopolysaccharide(LPS)-induced ALI was established to evaluate the therapeutic activity of PGD.The chemical makeup of PGD was analyzed using UPLC-Q-TOF-MS/MS and the active ingredients,hub targets,and key pathways involved in its action mechanism were determined using network pharmacology analysis.The hub targets and active ingredients were verified by molecular docking using Autodock Vina software.The mechanism by which PGD inhibits the PI3K/AKT/NF-κB signaling pathway was investigated via western blotting and quantitative real-time reverse transcription-polymerase chain reaction(RT-q PCR).Results: PGD ameliorated histopathological changes in lung tissues,decreased the total leukocyte count and total protein concentration in the bronchoalveolar lavage fluid,and attenuated levels of inflammatory factors in the bronchoalveolar lavage fluid(BALF),lung tissue,and serum.At the positive and negative ion scanning mode,70 components were identified.Network pharmacology analysis revealed the main ingredients to be glabridin,chrysin,3,3’-dimethyl quercetin,jaranol,isorhamnetin,hydroxygenkwanin,quercetin,acacetin,apigenin,and kaempferol.The core targets involved were GAPDH,TP53,AKT1,ALB,TNF,IL-6,VEGFA,EGFR,STAT3,and JUN,while the key pathways were PI3K/AKT and NF-κB.Molecular docking studies revealed an excellent level of binding between the active ingredients and the main targets.Western blotting and RT-q PCR experiments confirmed that PGD could reduce the expression of p-PI3K、p-AKT、 p-NF-κB、p-PI3K/PI3K、 p-AKT/AKT、and p-NF-κB/NF-κB and the m RNA expression of PI3K、AKT、and NF-κB.Conclusion: This study showed that PGD may alleviate LPS-induced ALI by modulating the PI3K/AKT/NF-κB pathway,downregulating the level of pro-inflammatory factors and weakening lung pathological damage.