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Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation

AIMS: Morinda officinalis oligosaccharides (MOOs), a traditional Chinese medicine, have been used to treat mild and moderate depressive episodes. In this study, we investigated whether MOOs can ameliorate depressive‐like behaviors in post‐stroke depression (PSD) rats and further explored its mechani...

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Autores principales: Li, Zhifang, Xu, Hexiang, Xu, Yi, Lu, Guanfeng, Peng, Qiwei, Chen, Jiefang, Bi, Rentang, Li, Jianzhuang, Chen, Shengcai, Li, Hongkai, Jin, Huijuan, Hu, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611777/
https://www.ncbi.nlm.nih.gov/pubmed/34559953
http://dx.doi.org/10.1111/cns.13732
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author Li, Zhifang
Xu, Hexiang
Xu, Yi
Lu, Guanfeng
Peng, Qiwei
Chen, Jiefang
Bi, Rentang
Li, Jianzhuang
Chen, Shengcai
Li, Hongkai
Jin, Huijuan
Hu, Bo
author_facet Li, Zhifang
Xu, Hexiang
Xu, Yi
Lu, Guanfeng
Peng, Qiwei
Chen, Jiefang
Bi, Rentang
Li, Jianzhuang
Chen, Shengcai
Li, Hongkai
Jin, Huijuan
Hu, Bo
author_sort Li, Zhifang
collection PubMed
description AIMS: Morinda officinalis oligosaccharides (MOOs), a traditional Chinese medicine, have been used to treat mild and moderate depressive episodes. In this study, we investigated whether MOOs can ameliorate depressive‐like behaviors in post‐stroke depression (PSD) rats and further explored its mechanism by suppressing microglial NLRP3 inflammasome activation to inhibit hippocampal inflammation. METHODS: Behavioral tests were performed to evaluate the effect of MOOs on depressive‐like behaviors in PSD rats. The effects of MOOs on the expression of IL‐18, IL‐1β, and nucleotide‐binding domain leucine‐rich repeat (NLR) family pyrin domain containing 3 (NLRP3) inflammasome were measured in both PSD rats and lipopolysaccharide (LPS) and adenosine triphosphate (ATP) stimulated primary rat microglia by reverse transcription polymerase chain reaction (RT‐PCR), immunofluorescence and Western blot analysis. Adeno‐associated virus (AAV) was injected into the hippocampus to regulate NLRP3 inflammasome expression. The detailed molecular mechanism underlying the effects of MOOs was analyzed by Western blot and immunofluorescence. RESULTS: MOOs can alleviate depressive‐like behaviors in PSD rats. PSD rats showed increased expression of IL‐18, IL‐1β, and NLRP3 inflammasome in the ischemic hippocampus, while MOOs reversed the elevation. NLRP3 downregulation ameliorated depressive‐like behaviors and hippocampal inflammation response in PSD rats, while NLRP3 upregulation inhibited the effect of MOOs on depressive‐like behaviors and hippocampal inflammation response in PSD rats. Moreover, we found that NLRP3 was mainly expressed on microglia. In vitro, MOOs effectively inhibited the expression of IL‐18, IL‐1β, and NLRP3 inflammasome in LPS + ATP treated primary rat microglia. We also showed that modulation of NLRP3 inflammasome by MOOs was associated with the IκB/NF‐κB p65 signaling pathway. CONCLUSION: Overall, our study reveals the antidepressive effect of MOOs on PSD rats through modulation of microglial NLRP3 inflammasome. We also provide a novel insight into hippocampal inflammation response in PSD pathology and put forward NLRP3 inflammasome as a potential therapeutic target for PSD.
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spelling pubmed-86117772021-11-30 Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation Li, Zhifang Xu, Hexiang Xu, Yi Lu, Guanfeng Peng, Qiwei Chen, Jiefang Bi, Rentang Li, Jianzhuang Chen, Shengcai Li, Hongkai Jin, Huijuan Hu, Bo CNS Neurosci Ther Original Articles AIMS: Morinda officinalis oligosaccharides (MOOs), a traditional Chinese medicine, have been used to treat mild and moderate depressive episodes. In this study, we investigated whether MOOs can ameliorate depressive‐like behaviors in post‐stroke depression (PSD) rats and further explored its mechanism by suppressing microglial NLRP3 inflammasome activation to inhibit hippocampal inflammation. METHODS: Behavioral tests were performed to evaluate the effect of MOOs on depressive‐like behaviors in PSD rats. The effects of MOOs on the expression of IL‐18, IL‐1β, and nucleotide‐binding domain leucine‐rich repeat (NLR) family pyrin domain containing 3 (NLRP3) inflammasome were measured in both PSD rats and lipopolysaccharide (LPS) and adenosine triphosphate (ATP) stimulated primary rat microglia by reverse transcription polymerase chain reaction (RT‐PCR), immunofluorescence and Western blot analysis. Adeno‐associated virus (AAV) was injected into the hippocampus to regulate NLRP3 inflammasome expression. The detailed molecular mechanism underlying the effects of MOOs was analyzed by Western blot and immunofluorescence. RESULTS: MOOs can alleviate depressive‐like behaviors in PSD rats. PSD rats showed increased expression of IL‐18, IL‐1β, and NLRP3 inflammasome in the ischemic hippocampus, while MOOs reversed the elevation. NLRP3 downregulation ameliorated depressive‐like behaviors and hippocampal inflammation response in PSD rats, while NLRP3 upregulation inhibited the effect of MOOs on depressive‐like behaviors and hippocampal inflammation response in PSD rats. Moreover, we found that NLRP3 was mainly expressed on microglia. In vitro, MOOs effectively inhibited the expression of IL‐18, IL‐1β, and NLRP3 inflammasome in LPS + ATP treated primary rat microglia. We also showed that modulation of NLRP3 inflammasome by MOOs was associated with the IκB/NF‐κB p65 signaling pathway. CONCLUSION: Overall, our study reveals the antidepressive effect of MOOs on PSD rats through modulation of microglial NLRP3 inflammasome. We also provide a novel insight into hippocampal inflammation response in PSD pathology and put forward NLRP3 inflammasome as a potential therapeutic target for PSD. John Wiley and Sons Inc. 2021-09-24 /pmc/articles/PMC8611777/ /pubmed/34559953 http://dx.doi.org/10.1111/cns.13732 Text en © 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Li, Zhifang
Xu, Hexiang
Xu, Yi
Lu, Guanfeng
Peng, Qiwei
Chen, Jiefang
Bi, Rentang
Li, Jianzhuang
Chen, Shengcai
Li, Hongkai
Jin, Huijuan
Hu, Bo
Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
title Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
title_full Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
title_fullStr Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
title_full_unstemmed Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
title_short Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation
title_sort morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing nlrp3 inflammasome to inhibit hippocampal inflammation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611777/
https://www.ncbi.nlm.nih.gov/pubmed/34559953
http://dx.doi.org/10.1111/cns.13732
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