UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study
Rheumatoid arthritis (RA) is characterized by systemic inflammation and synovial hyperplasia. Pristimerin, a natural triterpenoid isolated from plants belonging to the Celastraceae and Hippocrateaceae families, has been reported to exhibit anti-inflammation and anti-proliferation activities. Our stu...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-09-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/12/9/839 |
| _version_ | 1797484915347947520 |
|---|---|
| author | Mengying Lv Qiaoling Liang Zhaoyong Luo Bo Han Tengyang Ni Yang Wang Li Tao Weiting Lyu Jie Xiang Yanqing Liu |
| author_facet | Mengying Lv Qiaoling Liang Zhaoyong Luo Bo Han Tengyang Ni Yang Wang Li Tao Weiting Lyu Jie Xiang Yanqing Liu |
| author_sort | Mengying Lv |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is characterized by systemic inflammation and synovial hyperplasia. Pristimerin, a natural triterpenoid isolated from plants belonging to the Celastraceae and Hippocrateaceae families, has been reported to exhibit anti-inflammation and anti-proliferation activities. Our study aims to reveal the antiarthritic effects of pristimerin and explore its potential mechanism using in vitro, in silico, and in vivo methods. In the present study, pristimerin treatment led to a dose-dependent decrease in cell viability and migration in TNF-α stimulated human rheumatoid arthritis fibroblast-like synoviocytes MH7A. Moreover, UPLC-LTQ-Orbitrap-based cell metabolomics analysis demonstrated that phospholipid biosynthesis, fatty acid biosynthesis, glutathione metabolism and amino acid metabolic pathways were involved in TNF-α induced MH7A cells after pristimerin treatment. In addition, the adjuvant–induced arthritis (AIA) rat model was employed, and the results exhibited that pristimerin could effectively relieve arthritis symptoms and histopathological damage as well as reduce serum levels of TNF-α, NO and synovial expressions of p-Akt and p-Erk in AIA rats. Furthermore, network pharmacology analysis was performed to visualize crucial protein targets of pristimerin for RA treatment, which showed that the effects were mediated through the MAPK/Erk1/2, PI3K/Akt pathways and directing binding with TNF-α. Taken together, our study not only offered new insights into the biochemical mechanism of natural compounds for RA treatment, but also provided a strategy that integrated in vitro, in silico and in vivo studies to facilitate screening of new anti-RA drugs. |
| first_indexed | 2024-03-09T23:11:16Z |
| format | Article |
| id | doaj.art-ed8a67ba9c0848dc8ae0e05f89d47d47 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T23:11:16Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-ed8a67ba9c0848dc8ae0e05f89d47d472023-11-23T17:44:33ZengMDPI AGMetabolites2218-19892022-09-0112983910.3390/metabo12090839UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo StudyMengying Lv0Qiaoling Liang1Zhaoyong Luo2Bo Han3Tengyang Ni4Yang Wang5Li Tao6Weiting Lyu7Jie Xiang8Yanqing Liu9Department of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaDepartment of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaDepartment of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaKey Laboratory of Xinjiang Phytomedicine Resource and Utilization, School of Pharmacy, Ministry of Education, Shihezi University, Shihezi 832002, ChinaDepartment of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaDepartment of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaDepartment of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaDepartment of Medicinal Chemistry, Rutgers University, Piscataway, NJ 08854, USADepartment of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaDepartment of Pharmacy, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225001, ChinaRheumatoid arthritis (RA) is characterized by systemic inflammation and synovial hyperplasia. Pristimerin, a natural triterpenoid isolated from plants belonging to the Celastraceae and Hippocrateaceae families, has been reported to exhibit anti-inflammation and anti-proliferation activities. Our study aims to reveal the antiarthritic effects of pristimerin and explore its potential mechanism using in vitro, in silico, and in vivo methods. In the present study, pristimerin treatment led to a dose-dependent decrease in cell viability and migration in TNF-α stimulated human rheumatoid arthritis fibroblast-like synoviocytes MH7A. Moreover, UPLC-LTQ-Orbitrap-based cell metabolomics analysis demonstrated that phospholipid biosynthesis, fatty acid biosynthesis, glutathione metabolism and amino acid metabolic pathways were involved in TNF-α induced MH7A cells after pristimerin treatment. In addition, the adjuvant–induced arthritis (AIA) rat model was employed, and the results exhibited that pristimerin could effectively relieve arthritis symptoms and histopathological damage as well as reduce serum levels of TNF-α, NO and synovial expressions of p-Akt and p-Erk in AIA rats. Furthermore, network pharmacology analysis was performed to visualize crucial protein targets of pristimerin for RA treatment, which showed that the effects were mediated through the MAPK/Erk1/2, PI3K/Akt pathways and directing binding with TNF-α. Taken together, our study not only offered new insights into the biochemical mechanism of natural compounds for RA treatment, but also provided a strategy that integrated in vitro, in silico and in vivo studies to facilitate screening of new anti-RA drugs.https://www.mdpi.com/2218-1989/12/9/839pristimerinrheumatoid arthritiscell metabolomicsnetwork pharmacology analysisMH7Aadjuvant-induced arthritis |
| spellingShingle | Mengying Lv Qiaoling Liang Zhaoyong Luo Bo Han Tengyang Ni Yang Wang Li Tao Weiting Lyu Jie Xiang Yanqing Liu UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study Metabolites pristimerin rheumatoid arthritis cell metabolomics network pharmacology analysis MH7A adjuvant-induced arthritis |
| title | UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study |
| title_full | UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study |
| title_fullStr | UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study |
| title_full_unstemmed | UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study |
| title_short | UPLC-LTQ-Orbitrap-Based Cell Metabolomics and Network Pharmacology Analysis to Reveal the Potential Antiarthritic Effects of Pristimerin: In Vitro, In Silico and In Vivo Study |
| title_sort | uplc ltq orbitrap based cell metabolomics and network pharmacology analysis to reveal the potential antiarthritic effects of pristimerin in vitro in silico and in vivo study |
| topic | pristimerin rheumatoid arthritis cell metabolomics network pharmacology analysis MH7A adjuvant-induced arthritis |
| url | https://www.mdpi.com/2218-1989/12/9/839 |
| work_keys_str_mv | AT mengyinglv uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT qiaolingliang uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT zhaoyongluo uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT bohan uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT tengyangni uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT yangwang uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT litao uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT weitinglyu uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT jiexiang uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy AT yanqingliu uplcltqorbitrapbasedcellmetabolomicsandnetworkpharmacologyanalysistorevealthepotentialantiarthriticeffectsofpristimerininvitroinsilicoandinvivostudy |