Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation
BackgroundNeuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and im...
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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.2023.1178188/full |
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| author | Siyuan Xiong Siyuan Xiong Siyuan Xiong Xuyang Su Xuyang Su Xuyang Su Yingjie Kang Yingjie Kang Yingjie Kang Junqiang Si Junqiang Si Junqiang Si Lu Wang Lu Wang Lu Wang Xinzhi Li Xinzhi Li Xinzhi Li Ketao Ma Ketao Ma Ketao Ma |
| author_facet | Siyuan Xiong Siyuan Xiong Siyuan Xiong Xuyang Su Xuyang Su Xuyang Su Yingjie Kang Yingjie Kang Yingjie Kang Junqiang Si Junqiang Si Junqiang Si Lu Wang Lu Wang Lu Wang Xinzhi Li Xinzhi Li Xinzhi Li Ketao Ma Ketao Ma Ketao Ma |
| author_sort | Siyuan Xiong |
| collection | DOAJ |
| description | BackgroundNeuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and immunomodulatory activity.PurposeThe aim of this study was to elucidate the potential targets and molecular mechanisms of chlorogenic acid in the treatment of neuroinflammation.MethodsWe used the lipopolysaccharide-induced neuroinflammation mouse model and the lipopolysaccharide-stimulated BV-2 cells in vitro model. Behavioral scores and experiments were used to assess cognitive dysfunction in mice. HE staining and immunohistochemistry were used to assess neuronal damage in the mouse brain. Immunofluorescence detected microglia polarization in mouse brain. Western blot and flow cytometry detected the polarization of BV-2 cells. The migration of BV-2 cells was detected by wound healing assay and transwell assay. Potential targets for chlorogenic acid to exert protective effects were predicted by network pharmacology. These targets were then validated using molecular docking and experiments.ResultsThe results of in vivo experiments showed that chlorogenic acid had an obvious ameliorating effect on neuroinflammation-induced cognitive dysfunction. We found that chlorogenic acid was able to inhibit BV-2 cells M1 polarization and promote BV-2 cells M2 polarization in vitro while also inhibiting the abnormal migration of BV-2 cells. Based on the network pharmacology results, we identified the TNF signaling pathway as a key signaling pathway in which chlorogenic acid exerts anti-neuroinflammatory effects. Among them, Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA are the core targets for chlorogenic acid to function.ConclusionChlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway. |
| first_indexed | 2024-03-13T09:53:45Z |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T09:53:45Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-9dd3c25156054f4792055a5d3eafe7cb2023-05-24T04:44:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11781881178188Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammationSiyuan Xiong0Siyuan Xiong1Siyuan Xiong2Xuyang Su3Xuyang Su4Xuyang Su5Yingjie Kang6Yingjie Kang7Yingjie Kang8Junqiang Si9Junqiang Si10Junqiang Si11Lu Wang12Lu Wang13Lu Wang14Xinzhi Li15Xinzhi Li16Xinzhi Li17Ketao Ma18Ketao Ma19Ketao Ma20Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, ChinaNational Health Commission (NHC) Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathophysiology, Shihezi University School of Medicine, Shihezi, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, ChinaNational Health Commission (NHC) Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathophysiology, Shihezi University School of Medicine, Shihezi, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, ChinaNational Health Commission (NHC) Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Physiology, Shihezi University School of Medicine, Shihezi, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, ChinaNational Health Commission (NHC) Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Physiology, Shihezi University School of Medicine, Shihezi, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, ChinaNational Health Commission (NHC) Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pharmacology and Clinical Pharmacy, Shihezi University School of Pharmacy, Shihezi, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, ChinaNational Health Commission (NHC) Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Pathophysiology, Shihezi University School of Medicine, Shihezi, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, ChinaNational Health Commission (NHC) Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, ChinaDepartment of Physiology, Shihezi University School of Medicine, Shihezi, ChinaBackgroundNeuroinflammation is an important factor causing numerous neurodegenerative pathologies. Inflammation can lead to abnormal neuronal structure and function and even death, followed by cognitive dysfunction. There is growing evidence that chlorogenic acid has anti-inflammatory effects and immunomodulatory activity.PurposeThe aim of this study was to elucidate the potential targets and molecular mechanisms of chlorogenic acid in the treatment of neuroinflammation.MethodsWe used the lipopolysaccharide-induced neuroinflammation mouse model and the lipopolysaccharide-stimulated BV-2 cells in vitro model. Behavioral scores and experiments were used to assess cognitive dysfunction in mice. HE staining and immunohistochemistry were used to assess neuronal damage in the mouse brain. Immunofluorescence detected microglia polarization in mouse brain. Western blot and flow cytometry detected the polarization of BV-2 cells. The migration of BV-2 cells was detected by wound healing assay and transwell assay. Potential targets for chlorogenic acid to exert protective effects were predicted by network pharmacology. These targets were then validated using molecular docking and experiments.ResultsThe results of in vivo experiments showed that chlorogenic acid had an obvious ameliorating effect on neuroinflammation-induced cognitive dysfunction. We found that chlorogenic acid was able to inhibit BV-2 cells M1 polarization and promote BV-2 cells M2 polarization in vitro while also inhibiting the abnormal migration of BV-2 cells. Based on the network pharmacology results, we identified the TNF signaling pathway as a key signaling pathway in which chlorogenic acid exerts anti-neuroinflammatory effects. Among them, Akt1, TNF, MMP9, PTGS2, MAPK1, MAPK14, and RELA are the core targets for chlorogenic acid to function.ConclusionChlorogenic acid can inhibit microglial polarization toward the M1 phenotype and improve neuroinflammation-induced cognitive dysfunction in mice by modulating these key targets in the TNF signaling pathway.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178188/fullchlorogenic acidneuroinflammationcognitive dysfunctionmicrogliapolarizationTNF signaling pathway |
| spellingShingle | Siyuan Xiong Siyuan Xiong Siyuan Xiong Xuyang Su Xuyang Su Xuyang Su Yingjie Kang Yingjie Kang Yingjie Kang Junqiang Si Junqiang Si Junqiang Si Lu Wang Lu Wang Lu Wang Xinzhi Li Xinzhi Li Xinzhi Li Ketao Ma Ketao Ma Ketao Ma Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation Frontiers in Immunology chlorogenic acid neuroinflammation cognitive dysfunction microglia polarization TNF signaling pathway |
| title | Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation |
| title_full | Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation |
| title_fullStr | Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation |
| title_full_unstemmed | Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation |
| title_short | Effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide-induced neuroinflammation |
| title_sort | effect and mechanism of chlorogenic acid on cognitive dysfunction in mice by lipopolysaccharide induced neuroinflammation |
| topic | chlorogenic acid neuroinflammation cognitive dysfunction microglia polarization TNF signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178188/full |
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