Decoding the Mechanism of Magnolol in Treating Asthma Based on Network Pharmacology and Transcriptomic Analysis

作者全名:"Luo, L.; Wang, J. Y.; Xiong, A. Y.; Liu, J. L.; Liu, Y.; Liu, S. B.; Xiong, Y.; He, X.; Li, G. P."

作者地址:"Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Chengdu Inst Resp Hlth, Sch Med,Affiliated Hosp,Lab Allergy & Precis Med, Chengdu 610031, Peoples R China; [Luo, L.; Wang, J. Y.; Xiong, A. Y.; Liu, J. L.; Liu, Y.; Liu, S. B.; He, X.; Li, G. P.] ChongQing Med Univ, Chengdu Peoples Hosp 3, Dept Pulm & Crit Care Med, Affiliated Hosp,Branch Natl Clin Res Ctr Resp Dis, Chengdu 610031, Peoples R China; [Xiong, Y.] Sichuan Friendship Hosp, Dept Pulm & Crit Care Med, Chengdu 610000, Peoples R China"

通信作者:"He, X; Li, GP (通讯作者),ChongQing Med Univ, Chengdu Peoples Hosp 3, Dept Pulm & Crit Care Med, Affiliated Hosp,Branch Natl Clin Res Ctr Resp Dis, Chengdu 610031, Peoples R China.; Xiong, Y (通讯作者),Sichuan Friendship Hosp, Dept Pulm & Crit Care Med, Chengdu 610000, Peoples R China."

来源:INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES

ESI学科分类:PHARMACOLOGY & TOXICOLOGY

WOS号:WOS:001104167300026

JCR分区:Q4

影响因子:0.4

年份:2023

卷号:85

期号:5

开始页:1373

结束页:1387

文献类型:Article

关键词:Asthma; Magnolol; therapeutic targets; transcriptomics; network pharmacology

摘要:"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."

基金机构:"National Natural Science Foundation of China [81970026, 82000029, 82200079]; Natural Science Foundation of Sichuan [2022NSFCS 1324]; Chengdu High-level Key Clinical Specialty Construction Project [ZX20201202020]; Chengdu Science and Technology Bureau [2021-YF09-00102-SN, 2020-YF05-00003-SN]"

基金资助正文:"Data could be obtained upon request. This work was supported by the National Natural Science Foundation of China (81970026, 82000029, 82200079) , Natural Science Foundation of Sichuan (2022NSFCS 1324) , Chengdu High-level Key Clinical Specialty Construction Project (ZX20201202020) , Chengdu Science and Technology Bureau (2021-YF09-00102-SN, 2020-YF05-00003-SN) . The authors declare that they have no conflict of interest."