The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis
作者全名:"Qiaolongbatu, Xijier; Zhao, Wenjuan; Huang, Xucong; Qian, Feng; Yang, Xinyi; Wu, Jiaqi; Ma, Cui; Qu, Han; Wang, Li; Fan, Guorong; Wu, Zhenghua"
作者地址:"[Qiaolongbatu, Xijier; Zhao, Wenjuan; Qian, Feng; Yang, Xinyi; Qu, Han] Shanghai Jiao Tong Univ, Engn Res Ctr Cell & Therapeut Antibody, Pharm X 10, Sch Pharm,Minist Educ, Shanghai, Peoples R China; [Huang, Xucong; Wu, Jiaqi; Ma, Cui; Qu, Han; Fan, Guorong; Wu, Zhenghua] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Clin Pharm, Sch Med, Shanghai, Peoples R China; [Huang, Xucong; Wang, Li] Chongqing Med Univ, Sch Pharm, Chongqing, Peoples R China; [Fan, Guorong; Wu, Zhenghua] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Clin Pharm, 85 Wujin Rd, Shanghai 200080, Peoples R China"
通信作者:"Fan, GR; Wu, ZH (通讯作者),Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Clin Pharm, 85 Wujin Rd, Shanghai 200080, Peoples R China."
来源:DRUG DESIGN DEVELOPMENT AND THERAPY
ESI学科分类:PHARMACOLOGY & TOXICOLOGY
WOS号:WOS:000963497800001
JCR分区:Q1
影响因子:4.7
年份:2023
卷号:17
期号:
开始页:477
结束页:496
文献类型:Article
关键词:schisandrol A; pulmonary fibrosis; mechanism of action; network analysis; metabonomics
摘要:"Background: Schisandrol A (Sch A) is the main active ingredient of Schisandra chinensis (Turcz.) Baill. Our previous study showed that Sch A has anti-pulmonary fibrosis (PF) activity, but its metabolic-related mechanisms of action are not clear. Methods: Here, we explored the therapeutic mechanisms of Sch A on PF by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) metabolomics approach and network analysis. The metabolites of Sch A in mice (bleomycin + Sch A high-dose group) plasma were identified based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Results: 32 metabolites were detected reversed to normal level after treating bleomycin (BLM)-induced PF mice with Sch A. The 32 biomarkers were enriched in energy metabolism and several amino acid metabolisms, which was the first report on the therapeutic effects of Sch A on PF through rescuing the disordered energy metabolism. The UPLC-Q-TOF/MS analysis identified 17 possible metabolites (including isomers) of Sch A in mice plasma. Network analysis revealed that Sch A and 17 metabolites were related to 269 genes, and 1109 disease genes were related to PF. The construction of the Sch A/metabolites-target-PF network identified a total of 79 intersection genes and the TGF-beta signaling pathway was determined to be the main signaling pathway related to the treatment of PF by Sch A. The integrated approach involving metabolomics and network analysis revealed that the TGF-beta 1-ID3-creatine pathway, TGF-beta 1-VIM-carnosine pathway were two of the possible pathways Sch A regulated to modulate metabolic disorders, especially energy metabolism, and the metabolite of Sch A M5 was identified as a most likely active metabolite. Conclusion: The results suggested the feasibility of combining metabolomics and network analysis to reflect the effects of Sch A on the biological network and the metabolic state of PF and to evaluate the drug efficacy of Sch A and its related mechanisms."
基金机构:National Natural Science Foundation of China [81973289]; Shanghai key clinical discipline construction project [DY11.03.19.03]; Scientific and Innovative Action Plan of Shanghai [22S21902000]
基金资助正文:Acknowledgments This work is supported by the National Natural Science Foundation of China (81973289) ; Shanghai key clinical discipline construction project (02.DY11.03.19.03) ; Scientific and Innovative Action Plan of Shanghai (22S21902000) . The authors acknowledge the use of icons from BioRender.com (2020) to create schematic Graphical Abstract. Acknowledge Zhendong Pan for his contribution in the revision of the article.