Berberine attenuates depression-like behavior by modulating the hippocampal NLRP3 ubiquitination signaling pathway through Trim65
Copyright © 2023 Elsevier B.V. All rights reserved..
OBJECTIVE: Increasing evidence suggests that inflammation appears to play a role in the genesis of depression. Berberine has potent anti-inflammatory effects and potential antidepressant activity, although the mechanism by which it works is yet unclear. Our study aimed to investigate the molecular mechanisms through which berberine treats depression and reduces inflammation.
METHODS: The CUMS model and behavioral evaluation were utilized in this study to evaluate the efficacy of berberine in the treatment of depression. Berberine's effect on the inflammatory response in CUMS mice was evaluated via ELISA assays and western blotting. Nissl staining was used to observe hippocampal neuronal functional damage. Western blotting, ELISA, ubiquitination tests, and immunoprecipitation were utilized in conjunction with in vitro experiments to study the involvement of Trim65 in the antidepressant effects of berberine.
RESULTS: The results suggest that berberine effectively alleviates depressive symptoms, suppresses the expression of genes associated with the NLRP3 inflammasome (NLRP3, cleaved caspase-1, ASC, GSDMD-N, Pro-IL-1β, IL-1β, Pro-IL-18, and IL-18), and reduces hippocampal neuronal functional damage in CUMS mice. Further studies showed that knockdown of Trim65 reversed the effects of berberine and increased NLRP3 inflammasome activity. Finally, K285, an important site for Trim65 binding to NLRP3, was identified.
CONCLUSION: Our study describes the mechanism of berberine limiting NLRP3 inflammasome activity by promoting the conjugation of Trim65 to NLRP3 and NLRP3 ubiquitination, and suggests NLRP3 inflammasome activation as a prospective target for treating inflammation-associated disorders such as depression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:123 |
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| Enthalten in: |
International immunopharmacology - 123(2023) vom: 15. Okt., Seite 110808 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Lu [VerfasserIn] |
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| Links: |
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| Themen: |
0I8Y3P32UF |
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| Anmerkungen: |
Date Completed 22.09.2023 Date Revised 22.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2023.110808 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a OBJECTIVE: Increasing evidence suggests that inflammation appears to play a role in the genesis of depression. Berberine has potent anti-inflammatory effects and potential antidepressant activity, although the mechanism by which it works is yet unclear. Our study aimed to investigate the molecular mechanisms through which berberine treats depression and reduces inflammation | ||
| 520 | |a METHODS: The CUMS model and behavioral evaluation were utilized in this study to evaluate the efficacy of berberine in the treatment of depression. Berberine's effect on the inflammatory response in CUMS mice was evaluated via ELISA assays and western blotting. Nissl staining was used to observe hippocampal neuronal functional damage. Western blotting, ELISA, ubiquitination tests, and immunoprecipitation were utilized in conjunction with in vitro experiments to study the involvement of Trim65 in the antidepressant effects of berberine | ||
| 520 | |a RESULTS: The results suggest that berberine effectively alleviates depressive symptoms, suppresses the expression of genes associated with the NLRP3 inflammasome (NLRP3, cleaved caspase-1, ASC, GSDMD-N, Pro-IL-1β, IL-1β, Pro-IL-18, and IL-18), and reduces hippocampal neuronal functional damage in CUMS mice. Further studies showed that knockdown of Trim65 reversed the effects of berberine and increased NLRP3 inflammasome activity. Finally, K285, an important site for Trim65 binding to NLRP3, was identified | ||
| 520 | |a CONCLUSION: Our study describes the mechanism of berberine limiting NLRP3 inflammasome activity by promoting the conjugation of Trim65 to NLRP3 and NLRP3 ubiquitination, and suggests NLRP3 inflammasome activation as a prospective target for treating inflammation-associated disorders such as depression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Berberine | |
| 650 | 4 | |a Depression | |
| 650 | 4 | |a NLRP3 | |
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| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 700 | 1 | |a Huang, Yuzhen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Fengxi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Kunhan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Weiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Wanli |e verfasserin |4 aut | |
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