The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis
Xijier Qiaolongbatu,1,* Wenjuan Zhao,1,* Xucong Huang,2,3,* Feng Qian,1 Xinyi Yang,1 Jiaqi Wu,2 Cui Ma,2 Han Qu,1,2 Li Wang,3 Guorong Fan,2 Zhenghua Wu2 1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy,...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2023-02-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/the-therapeutic-mechanism-of-schisandrol-a-and-its-metabolites-on-pulm-peer-reviewed-fulltext-article-DDDT |
| _version_ | 1811164161139277824 |
|---|---|
| author | Qiaolongbatu X Zhao W Huang X Qian F Yang X Wu J Ma C Qu H Wang L Fan G Wu Z |
| author_facet | Qiaolongbatu X Zhao W Huang X Qian F Yang X Wu J Ma C Qu H Wang L Fan G Wu Z |
| author_sort | Qiaolongbatu X |
| collection | DOAJ |
| description | Xijier Qiaolongbatu,1,* Wenjuan Zhao,1,* Xucong Huang,2,3,* Feng Qian,1 Xinyi Yang,1 Jiaqi Wu,2 Cui Ma,2 Han Qu,1,2 Li Wang,3 Guorong Fan,2 Zhenghua Wu2 1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3School of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua Wu; Guorong Fan, Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-133-0177-7863 ; +86-21-36123711, Email zhenghua.wu@shgh.cn; fanguorong@sjtu.edu.cnBackground: 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-β 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-β 1-ID3-creatine pathway, TGF-β 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.Graphical Abstract: Keywords: schisandrol A, pulmonary fibrosis, mechanism of action, network analysis, metabonomics |
| first_indexed | 2024-04-10T15:16:51Z |
| format | Article |
| id | doaj.art-119000783ac84937abcd0a986a9ec611 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-04-10T15:16:51Z |
| publishDate | 2023-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-119000783ac84937abcd0a986a9ec6112023-02-14T18:00:38ZengDove Medical PressDrug Design, Development and Therapy1177-88812023-02-01Volume 1747749681643The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network AnalysisQiaolongbatu XZhao WHuang XQian FYang XWu JMa CQu HWang LFan GWu ZXijier Qiaolongbatu,1,* Wenjuan Zhao,1,* Xucong Huang,2,3,* Feng Qian,1 Xinyi Yang,1 Jiaqi Wu,2 Cui Ma,2 Han Qu,1,2 Li Wang,3 Guorong Fan,2 Zhenghua Wu2 1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3School of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua Wu; Guorong Fan, Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-133-0177-7863 ; +86-21-36123711, Email zhenghua.wu@shgh.cn; fanguorong@sjtu.edu.cnBackground: 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-β 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-β 1-ID3-creatine pathway, TGF-β 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.Graphical Abstract: Keywords: schisandrol A, pulmonary fibrosis, mechanism of action, network analysis, metabonomicshttps://www.dovepress.com/the-therapeutic-mechanism-of-schisandrol-a-and-its-metabolites-on-pulm-peer-reviewed-fulltext-article-DDDTschisandrol apulmonary fibrosismechanism of actionnetwork analysismetabonomics |
| spellingShingle | Qiaolongbatu X Zhao W Huang X Qian F Yang X Wu J Ma C Qu H Wang L Fan G Wu Z The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis Drug Design, Development and Therapy schisandrol a pulmonary fibrosis mechanism of action network analysis metabonomics |
| title | The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis |
| title_full | The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis |
| title_fullStr | The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis |
| title_full_unstemmed | The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis |
| title_short | The Therapeutic Mechanism of Schisandrol A and Its Metabolites on Pulmonary Fibrosis Based on Plasma Metabonomics and Network Analysis |
| title_sort | therapeutic mechanism of schisandrol a and its metabolites on pulmonary fibrosis based on plasma metabonomics and network analysis |
| topic | schisandrol a pulmonary fibrosis mechanism of action network analysis metabonomics |
| url | https://www.dovepress.com/the-therapeutic-mechanism-of-schisandrol-a-and-its-metabolites-on-pulm-peer-reviewed-fulltext-article-DDDT |
| work_keys_str_mv | AT qiaolongbatux thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT zhaow thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT huangx thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT qianf thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT yangx thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT wuj thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT mac thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT quh thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT wangl thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT fang thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT wuz thetherapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT qiaolongbatux therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT zhaow therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT huangx therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT qianf therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT yangx therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT wuj therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT mac therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT quh therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT wangl therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT fang therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis AT wuz therapeuticmechanismofschisandrolaanditsmetabolitesonpulmonaryfibrosisbasedonplasmametabonomicsandnetworkanalysis |