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Article: Botanical Drug Puerarin Ameliorates Liposaccharide-Induced Depressive Behaviors in Mice via Inhibiting RagA/mTOR/p70S6K Pathways

TitleBotanical Drug Puerarin Ameliorates Liposaccharide-Induced Depressive Behaviors in Mice via Inhibiting RagA/mTOR/p70S6K Pathways
Authors
KeywordsAnimals
Antidepressive Agents
Behavior, Animal
Brain
Cytokines
Issue Date2021
PublisherHindawi. The Journal's web site is located at http://www.hindawi.com/journals/oximed/
Citation
Oxidative Medicine and Cellular Longevity, 2021, v. 2021, article no. 7716201 How to Cite?
AbstractBackground: The depressive symptom hallmarks the progression of the neurodegenerative diseases, especially Alzheimer's disease. Bacterial infection is related to inflammation and depression. The present project thereby examined whether botanical drug puerarin could attenuate liposaccharide- (LPS-) induced depressive behaviors in mice. Methods: Adult male C57BL/6N mice were sequentially treated with LPS and puerarin and evaluated for the depressive behaviors by tail suspension test and forced swim test. The brain tissues were profiled for the molecular targets of puerarin by next-generation RNA sequencing technique. Candidate targets were further verified in LPS-treated mice, neural stem cells, and highly differentiated PC12 cell line. Results: Puerarin ameliorated LPS-induced depression in the mice. RNA sequencing profiles revealed that puerarin altered the expression of 16 genes while markedly downregulated Ras-related GTP-binding protein A (RagA) in LPS-treated mice. The effect of puerarin on RagA expression was confirmed by immunostaining, Western blot, and quantitative real-time PCR (qRT-PCR). Biochemical studies showed that puerarin inhibited RagA/mTOR/p70S6K pathway, attenuated the accumulation of mTORC1 in close proximity to lysosome, and reduced the production of proinflammatory cytokines. Conclusions: Botanical drug puerarin attenuated inflammation and depressive behaviors in LPS-challenged mice by inhibiting RagA/mTOR/p70S6K pathways. Puerarin may be a lead compound for the new antidepressant drugs.
Persistent Identifierhttp://hdl.handle.net/10722/313853
ISSN
2021 Impact Factor: 7.310
2023 SCImago Journal Rankings: 1.477
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhao, J-
dc.contributor.authorJia, Y-
dc.contributor.authorZhao, W-
dc.contributor.authorChen, HS-
dc.contributor.authorZHANG, X-
dc.contributor.authorNGO, FY-
dc.contributor.authorLuo, D-
dc.contributor.authorSong, Y-
dc.contributor.authorLao, L-
dc.contributor.authorRong, J-
dc.date.accessioned2022-07-05T05:07:00Z-
dc.date.available2022-07-05T05:07:00Z-
dc.date.issued2021-
dc.identifier.citationOxidative Medicine and Cellular Longevity, 2021, v. 2021, article no. 7716201-
dc.identifier.issn1942-0900-
dc.identifier.urihttp://hdl.handle.net/10722/313853-
dc.description.abstractBackground: The depressive symptom hallmarks the progression of the neurodegenerative diseases, especially Alzheimer's disease. Bacterial infection is related to inflammation and depression. The present project thereby examined whether botanical drug puerarin could attenuate liposaccharide- (LPS-) induced depressive behaviors in mice. Methods: Adult male C57BL/6N mice were sequentially treated with LPS and puerarin and evaluated for the depressive behaviors by tail suspension test and forced swim test. The brain tissues were profiled for the molecular targets of puerarin by next-generation RNA sequencing technique. Candidate targets were further verified in LPS-treated mice, neural stem cells, and highly differentiated PC12 cell line. Results: Puerarin ameliorated LPS-induced depression in the mice. RNA sequencing profiles revealed that puerarin altered the expression of 16 genes while markedly downregulated Ras-related GTP-binding protein A (RagA) in LPS-treated mice. The effect of puerarin on RagA expression was confirmed by immunostaining, Western blot, and quantitative real-time PCR (qRT-PCR). Biochemical studies showed that puerarin inhibited RagA/mTOR/p70S6K pathway, attenuated the accumulation of mTORC1 in close proximity to lysosome, and reduced the production of proinflammatory cytokines. Conclusions: Botanical drug puerarin attenuated inflammation and depressive behaviors in LPS-challenged mice by inhibiting RagA/mTOR/p70S6K pathways. Puerarin may be a lead compound for the new antidepressant drugs.-
dc.languageeng-
dc.publisherHindawi. The Journal's web site is located at http://www.hindawi.com/journals/oximed/-
dc.relation.ispartofOxidative Medicine and Cellular Longevity-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAnimals-
dc.subjectAntidepressive Agents-
dc.subjectBehavior, Animal-
dc.subjectBrain-
dc.subjectCytokines-
dc.titleBotanical Drug Puerarin Ameliorates Liposaccharide-Induced Depressive Behaviors in Mice via Inhibiting RagA/mTOR/p70S6K Pathways-
dc.typeArticle-
dc.identifier.emailZhao, J: zhaojia7@hku.hk-
dc.identifier.emailSong, Y: songy@hku.hk-
dc.identifier.emailRong, J: jrong@hku.hk-
dc.identifier.authoritySong, Y=rp00488-
dc.identifier.authorityLao, L=rp01784-
dc.identifier.authorityRong, J=rp00515-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1155/2021/7716201-
dc.identifier.pmid34707778-
dc.identifier.pmcidPMC8545548-
dc.identifier.hkuros333971-
dc.identifier.volume2021-
dc.identifier.spagearticle no. 7716201-
dc.identifier.epagearticle no. 7716201-
dc.identifier.isiWOS:000721503200002-
dc.publisher.placeGreat Britain-

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