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        Inhalation of panaxadiol alleviates lung infl ammation via inhibiting TNFA/ TNFAR and IL7/IL7R signaling between macrophages and epithelial cells

        Yifan Wang,Hao Wei,Zhen Song,Liqun Jiang,Mi Zhang,Xiao Lu,Wei Li,Yuqing Zhao,Lei Wu,Shuxian Li,Huijuan Shen,Qiang Shu,Yicheng Xie 고려인삼학회 2024 Journal of Ginseng Research Vol.48 No.1

        Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng andits derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic propertieshinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalationadministration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophageinflammation model, and a coculture model of epithelial cells and macrophages were used to study the effectsand mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy andmechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, includinginflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose ofinhalation was much lower than that of intragastric administration under the same therapeutic effect, which maybe related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysisand verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibitingTNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosisand promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7Rsignaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lunginflammation.

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