iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice
Abstract ACT001 is a novel sesquiterpene lactone derivative that has been shown to have significant antitumor and anti-inflammatory effects. However, the effect of ACT001 on nonalcoholic steatohepatitis (NASH) is unknown. Methionine and choline deficient (MCD) diet induced NASH model in C57BL/6J mic...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-38448-4 |
| _version_ | 1797779005464641536 |
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| author | Hui Zhou Bin Niu Xue Wu Weike Chu Yibing Zhou Ze Chen Yuqiang Mi Yonggang Liu Ping Li |
| author_facet | Hui Zhou Bin Niu Xue Wu Weike Chu Yibing Zhou Ze Chen Yuqiang Mi Yonggang Liu Ping Li |
| author_sort | Hui Zhou |
| collection | DOAJ |
| description | Abstract ACT001 is a novel sesquiterpene lactone derivative that has been shown to have significant antitumor and anti-inflammatory effects. However, the effect of ACT001 on nonalcoholic steatohepatitis (NASH) is unknown. Methionine and choline deficient (MCD) diet induced NASH model in C57BL/6J mice. Steatosis, inflammation and fibrosis-related indices of serum and liver tissues were detected by fully automated biochemical analyzer, enzyme-linked immunosorbent assay (ELISA) kit, flow cytometry, hematoxylin and eosin (H&E), Masson and immunohistochemical staining. The results showed that ACT001 reduced serum lipid and inflammatory factor levels, attenuated hepatic steatosis, inflammation and fibrosis, and inhibited hepatic oxidative stress and activation of NOD-like receptor protein 3 (NLRP3) inflammatory vesicles in NASH mice. In addition, 381 differentially expressed proteins (DEPs), including 162 up-regulated and 219 down-regulated proteins, were identified in the MCD group and ACT001 high-dose group using isotope labeling relative and absolute quantification (iTRAQ) technique analysis. Among these DEPs, five proteins associated with NAFLD were selected for real-time fluorescence quantitative PCR (RT-qPCR) validation, and the results were consistent with proteomics. In conclusion, ACT001 has a therapeutic effect on NASH, and the results of proteomic analysis will provide new ideas for the mechanism study of ACT001 for NASH treatment. |
| first_indexed | 2024-03-12T23:24:34Z |
| format | Article |
| id | doaj.art-c57e3441ceef4dbaa1d672b7ebe84230 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-12T23:24:34Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c57e3441ceef4dbaa1d672b7ebe842302023-07-16T11:14:12ZengNature PortfolioScientific Reports2045-23222023-07-0113111710.1038/s41598-023-38448-4iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in miceHui Zhou0Bin Niu1Xue Wu2Weike Chu3Yibing Zhou4Ze Chen5Yuqiang Mi6Yonggang Liu7Ping Li8Clinical School of the Second People’s Hospital, Tianjin Medical UniversityClinical School of the Second People’s Hospital, Tianjin Medical UniversityClinical School of the Second People’s Hospital, Tianjin Medical UniversityClinical School of the Second People’s Hospital, Tianjin Medical UniversityClinical School of the Second People’s Hospital, Tianjin Medical UniversityClinical School of the Second People’s Hospital, Tianjin Medical UniversityClinical School of the Second People’s Hospital, Tianjin Medical UniversityDepartment of Pathology, Tianjin Second People’s HospitalClinical School of the Second People’s Hospital, Tianjin Medical UniversityAbstract ACT001 is a novel sesquiterpene lactone derivative that has been shown to have significant antitumor and anti-inflammatory effects. However, the effect of ACT001 on nonalcoholic steatohepatitis (NASH) is unknown. Methionine and choline deficient (MCD) diet induced NASH model in C57BL/6J mice. Steatosis, inflammation and fibrosis-related indices of serum and liver tissues were detected by fully automated biochemical analyzer, enzyme-linked immunosorbent assay (ELISA) kit, flow cytometry, hematoxylin and eosin (H&E), Masson and immunohistochemical staining. The results showed that ACT001 reduced serum lipid and inflammatory factor levels, attenuated hepatic steatosis, inflammation and fibrosis, and inhibited hepatic oxidative stress and activation of NOD-like receptor protein 3 (NLRP3) inflammatory vesicles in NASH mice. In addition, 381 differentially expressed proteins (DEPs), including 162 up-regulated and 219 down-regulated proteins, were identified in the MCD group and ACT001 high-dose group using isotope labeling relative and absolute quantification (iTRAQ) technique analysis. Among these DEPs, five proteins associated with NAFLD were selected for real-time fluorescence quantitative PCR (RT-qPCR) validation, and the results were consistent with proteomics. In conclusion, ACT001 has a therapeutic effect on NASH, and the results of proteomic analysis will provide new ideas for the mechanism study of ACT001 for NASH treatment.https://doi.org/10.1038/s41598-023-38448-4 |
| spellingShingle | Hui Zhou Bin Niu Xue Wu Weike Chu Yibing Zhou Ze Chen Yuqiang Mi Yonggang Liu Ping Li iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice Scientific Reports |
| title | iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice |
| title_full | iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice |
| title_fullStr | iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice |
| title_full_unstemmed | iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice |
| title_short | iTRAQ-based quantitative proteomics analysis of the effect of ACT001 on non-alcoholic steatohepatitis in mice |
| title_sort | itraq based quantitative proteomics analysis of the effect of act001 on non alcoholic steatohepatitis in mice |
| url | https://doi.org/10.1038/s41598-023-38448-4 |
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