Abstract

Author(s): L. Luo1, J. Y. Wang1, A. Y. Xiong1, J. L. Liu1, Y. Liu1, S.B. Liu1, Y. Xiong, X. He and G. P. Li*
School of Medicine, Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, 1Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, 2Department of Pulmonary and Critical Care Medicine, Sichuan Friendship Hospital, Chengdu 610000, Chi na

Correspondence Address:
G. P. Li, Department of Pulmonary and Critical Care Medicine, Chengdu Third People’s Hospital branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu 610031, China, E-mail: lzlgp@163.com

Magnolol is an active polyphenol extracted from the traditional Chinese herb Magnolia officinalis, which can be applied for expectorating phlegm and relieving cough. However, the role and molecular mechanism of Magnolol in the treatment of asthma was not fully explored. To comprehensively analyze the pharmacological targets of Magnolol, ovalbumin-induced asthmatic mice model was established, and subsequently conducted with Magnolol. The pathological changes of lung tissue were observed by Haematoxylin and Eosin, periodic acid-Schiff stain and Masson's trichrome staining. Network pharmacology combined with the transcriptomic analysis was applied to investigate the underlying mechanisms and targets. Potential targets were validated by quantitative reverse transcription polymerase chain reaction and immunofluorescence in vivo. As a result, this study found that the inflammatory infiltrations in Magnolol-treated asthma mice were significantly ameliorated. Using network pharmacology, it was identified 33 asthma-related Magnolol targets, which obviously involved in positive regulation of cytokine production and Th17 cell differentiation pathways. Furthermore, the transcriptome analysis showed that the infiltration score of eosinophils, activated mast cells and M1 macrophages were significantly decreased in Magnolol-treated asthmatic mice. Meanwhile, Hallmark analysis exhibited that the enrichment scores of interferon gamma and alpha responses were remarkably enhanced in Magnolol treated ovalbumin-induced asthmatic mice. Moreover, the potential therapeutic targets, Arginase 1, Phosphodiesterase 4B, Signal transducer and activator of transcription 1 and Matrix metallopeptidase 12 were screened out by using combined analysis of asthma targets, Magnolol targets and differential expressed genes. In particular, gene set enrichment analysis revealed that high Matrix metallopeptidase 12 expression was associated with asthma and cytokine-cytokine receptor interaction pathways. The expression of Matrix metallopeptidase 12 was significantly decreased in asthma group and was restored after Magnolol treatment through quantitative reverse transcription polymerase chain reaction and immunofluorescence validation. Together, this study found that Magnolol might have a therapeutic effect on asthma by regulation of Matrix metallopeptidase 12 through cytokine mediated signaling pathway.

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