Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming
Inflammation is thought to be a key cause of many chronic diseases and cancer. However, current therapeutic agents to control inflammation have limited long-term use potential due to various side-effects. This study aimed to examine the preventive effects of norbergenin, a constituent of traditional...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1117638/full |
| _version_ | 1827949637337612288 |
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| author | Wan Li Wan Li Zhengnan Cai Zhengnan Cai Florian Schindler Florian Schindler Sheyda Bahiraii Sheyda Bahiraii Martin Brenner Martin Brenner Martin Brenner Elke H. Heiss Wolfram Weckwerth Wolfram Weckwerth |
| author_facet | Wan Li Wan Li Zhengnan Cai Zhengnan Cai Florian Schindler Florian Schindler Sheyda Bahiraii Sheyda Bahiraii Martin Brenner Martin Brenner Martin Brenner Elke H. Heiss Wolfram Weckwerth Wolfram Weckwerth |
| author_sort | Wan Li |
| collection | DOAJ |
| description | Inflammation is thought to be a key cause of many chronic diseases and cancer. However, current therapeutic agents to control inflammation have limited long-term use potential due to various side-effects. This study aimed to examine the preventive effects of norbergenin, a constituent of traditional anti-inflammatory recipes, on LPS-induced proinflammatory signaling in macrophages and elucidate the underlying mechanisms by integrative metabolomics and shotgun label-free quantitative proteomics platforms. Using high-resolution mass spectrometry, we identified and quantified nearly 3000 proteins across all samples in each dataset. To interpret these datasets, we exploited the differentially expressed proteins and conducted statistical analyses. Accordingly, we found that LPS-induced production of NO, IL1β, TNFα, IL6 and iNOS in macrophages was alleviated by norbergenin via suppressed activation of TLR2 mediated NFκB, MAPKs and STAT3 signaling pathways. In addition, norbergenin was capable of overcoming LPS-triggered metabolic reprogramming in macrophages and restrained the facilitated glycolysis, promoted OXPHOS, and restored the aberrant metabolites within the TCA cycle. This is linked to its modulation of metabolic enzymes to support its anti-inflammatory activity. Thus, our results uncover that norbergenin regulates inflammatory signaling cascades and metabolic reprogramming in LPS stimulated macrophages to exert its anti-inflammatory potential. |
| first_indexed | 2024-04-09T13:14:14Z |
| format | Article |
| id | doaj.art-1bce8259c0d547f6a3eb107e1aab0f94 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T13:14:14Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1bce8259c0d547f6a3eb107e1aab0f942023-05-12T04:40:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11176381117638Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogrammingWan Li0Wan Li1Zhengnan Cai2Zhengnan Cai3Florian Schindler4Florian Schindler5Sheyda Bahiraii6Sheyda Bahiraii7Martin Brenner8Martin Brenner9Martin Brenner10Elke H. Heiss11Wolfram Weckwerth12Wolfram Weckwerth13Molecular Systems Biology (MOSYS), Department of Functional and Evolutionary Ecology, University of Vienna, Vienna, AustriaVienna Doctoral School of Ecology and Evolution, University of Vienna, Vienna, AustriaMolecular Systems Biology (MOSYS), Department of Functional and Evolutionary Ecology, University of Vienna, Vienna, AustriaVienna Doctoral School of Ecology and Evolution, University of Vienna, Vienna, AustriaMolecular Systems Biology (MOSYS), Department of Functional and Evolutionary Ecology, University of Vienna, Vienna, AustriaVienna Doctoral School of Pharmaceutical, Nutritional and Sports Sciences, University of Vienna, Vienna, AustriaVienna Doctoral School of Pharmaceutical, Nutritional and Sports Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Sciences, University of Vienna, Vienna, AustriaMolecular Systems Biology (MOSYS), Department of Functional and Evolutionary Ecology, University of Vienna, Vienna, AustriaVienna Doctoral School of Pharmaceutical, Nutritional and Sports Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Sciences, University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Sciences, University of Vienna, Vienna, AustriaMolecular Systems Biology (MOSYS), Department of Functional and Evolutionary Ecology, University of Vienna, Vienna, AustriaVienna Metabolomics Center (VIME), University of Vienna, Vienna, AustriaInflammation is thought to be a key cause of many chronic diseases and cancer. However, current therapeutic agents to control inflammation have limited long-term use potential due to various side-effects. This study aimed to examine the preventive effects of norbergenin, a constituent of traditional anti-inflammatory recipes, on LPS-induced proinflammatory signaling in macrophages and elucidate the underlying mechanisms by integrative metabolomics and shotgun label-free quantitative proteomics platforms. Using high-resolution mass spectrometry, we identified and quantified nearly 3000 proteins across all samples in each dataset. To interpret these datasets, we exploited the differentially expressed proteins and conducted statistical analyses. Accordingly, we found that LPS-induced production of NO, IL1β, TNFα, IL6 and iNOS in macrophages was alleviated by norbergenin via suppressed activation of TLR2 mediated NFκB, MAPKs and STAT3 signaling pathways. In addition, norbergenin was capable of overcoming LPS-triggered metabolic reprogramming in macrophages and restrained the facilitated glycolysis, promoted OXPHOS, and restored the aberrant metabolites within the TCA cycle. This is linked to its modulation of metabolic enzymes to support its anti-inflammatory activity. Thus, our results uncover that norbergenin regulates inflammatory signaling cascades and metabolic reprogramming in LPS stimulated macrophages to exert its anti-inflammatory potential.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1117638/fullnorbergeninanti-inflammationproteomicsmetabolomicsmacrophagesNFκB signaling pathway |
| spellingShingle | Wan Li Wan Li Zhengnan Cai Zhengnan Cai Florian Schindler Florian Schindler Sheyda Bahiraii Sheyda Bahiraii Martin Brenner Martin Brenner Martin Brenner Elke H. Heiss Wolfram Weckwerth Wolfram Weckwerth Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming Frontiers in Immunology norbergenin anti-inflammation proteomics metabolomics macrophages NFκB signaling pathway |
| title | Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming |
| title_full | Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming |
| title_fullStr | Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming |
| title_full_unstemmed | Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming |
| title_short | Norbergenin prevents LPS-induced inflammatory responses in macrophages through inhibiting NFκB, MAPK and STAT3 activation and blocking metabolic reprogramming |
| title_sort | norbergenin prevents lps induced inflammatory responses in macrophages through inhibiting nfκb mapk and stat3 activation and blocking metabolic reprogramming |
| topic | norbergenin anti-inflammation proteomics metabolomics macrophages NFκB signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1117638/full |
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