Polygala saponins inhibit NLRP3 inflammasome-mediated neuroinflammation via SHP-2-Mediated mitophagy.

Animals Inflammasomes Mice Mitophagy NLR Family, Pyrin Domain-Containing 3 Protein / genetics Neuroinflammatory Diseases Polygala Saponins / pharmacology
Mitophagy NLRP3 inflammasome Neurodegenerative disease Polygala saponins Radix polygalae SHP-2

Journal

Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159

Informations de publication

Date de publication:
01 02 2022
Historique:
received: 28 06 2021
revised: 02 12 2021
accepted: 15 12 2021
pubmed: 22 12 2021
medline: 1 2 2022
entrez: 21 12 2021
Statut: ppublish

Résumé

Activation of the NLRP3 inflammasome and its mediated neuroinflammation are implicated in neurodegenerative diseases, while mitophagy negatively regulates NLRP3 inflammasome activation. SHP-2, a protein-tyrosine phosphatase, is critical for NLRP3 inflammasome regulation and inflammatory responses. In this study, we investigated whether triterpenoid saponins in Radix Polygalae inhibit the NLRP3 inflammasome via mitophagy induction. First, we isolated the active fraction (polygala saponins (PSS)) and identified 17 saponins by ultra-performance liquid chromatography coupled with diode-array detection and tandem quadrupole time-of-flight mass spectrometry (UHPLC-DAD-Q/TOF-MS). In microglial BV-2 cells, PSS induced mitophagy as evidenced by increased co-localization of LC3 and mitochondria, as well as an increased number of autophagic vacuoles surrounding the mitochondria. Furthermore, the mechanistic study found that PSS activated the AMPK/mTOR and PINK1/parkin signaling pathways via the upregulation of SHP-2. In Aβ(1-42)-, A53T-α-synuclein-, or Q74-induced BV-2 cells, PSS significantly inhibited NLRP3 inflammasome activation, which was attenuated by bafilomycin A1 (an autophagy inhibitor) and SHP099 (an SHP-2 inhibitor). In addition, the co-localization of LC3 and ASC revealed that PSS promoted the autophagic degradation of the NLRP3 inflammasome. Moreover, PSS decreased apoptosis in conditioned medium-induced PC-12 cells. In APP/PS1 mice, PSS improved cognitive function, ameliorated Aβ pathology, and inhibited neuronal death. Collectively, the present study, for the first time, shows that PSS inhibit the NLRP3 inflammasome via SHP-2-mediated mitophagy in vitro and in vivo, which strongly suggests the therapeutic potential of PSS in various neurodegenerative diseases.

Identifiants

DOI: 10.1016/j.freeradbiomed.2021.12.263 PMID: 34933095
pubmed: 34933095
pii: S0891-5849(21)01115-1
doi: 10.1016/j.freeradbiomed.2021.12.263
pii:
doi:

Substances chimiques

Inflammasomes 0
NLR Family, Pyrin Domain-Containing 3 Protein 0
Nlrp3 protein, mouse 0
Saponins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

76-94

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Auteurs

Wen-Qiao Qiu (WQ)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China; Department of Neurosurgery Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610000, China. Electronic address: fanny.qiu@outlook.com.

Wei Ai (W)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: swmuaw@126.com.

Feng-Dan Zhu (FD)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: lethe19970801@163.com.

Yue Zhang (Y)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: zhangyuechanyeol@163.com.

Min-Song Guo (MS)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: dididigms@163.com.

Betty Yuen-Kwan Law (BY)

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao. Electronic address: yklaw@must.edu.mo.

Jian-Ming Wu (JM)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China; Education Ministry Key Laboratory of Medical Electrophysiology, College of Preclinical Medicine, Southwest Medical University, Luzhou, China. Electronic address: jianmingwu@swmu.edu.cn.

Vincent Kam-Wai Wong (VK)

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao. Electronic address: kawwong@must.edu.mo.

Yong Tang (Y)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao. Electronic address: tangy1989@yeah.net.

Lu Yu (L)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: yulu863@swmu.edu.cn.

Qi Chen (Q)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China; Department of Nursing, Affiliated Hospital of Southwest Medical University, Luzhou, China. Electronic address: qichen@swmu.edu.cn.

Chong-Lin Yu (CL)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: 8056ycl@swmu.edu.cn.

Jian Liu (J)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: belkn@swmu.edu.cn.

Da-Lian Qin (DL)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China; Education Ministry Key Laboratory of Medical Electrophysiology, College of Preclinical Medicine, Southwest Medical University, Luzhou, China. Electronic address: dalianqin@swmu.edu.cn.

Xiao-Gang Zhou (XG)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: zxg@swmu.edu.cn.

An-Guo Wu (AG)

Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, China; Education Ministry Key Laboratory of Medical Electrophysiology, College of Preclinical Medicine, Southwest Medical University, Luzhou, China. Electronic address: wuanguo@swmu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Polygala saponins inhibit NLRP3...
questionsmedicales.fr › Structures macromoléculaires › Complexes multiprotéiques › Inflammasomes › Polygala saponins inhibit NLRP3...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Polygala saponins inhibit NLRP3...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Renouvellement des mitochondries › Dégradation des mitochondries › Polygala saponins inhibit NLRP3...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Protéines NLR › Protéine-3 de la famille des NLR contenant un domaine pyrine › Polygala saponins inhibit NLRP3...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Maladies neuro-inflammatoires › Polygala saponins inhibit NLRP3...
questionsmedicales.fr › Eucaryotes › Viridiplantae › Streptophyta › Embryophyta › Tracheobionta › Magnoliopsida › Rosanae › Polygalaceae › Polygala › Polygala saponins inhibit NLRP3...
questionsmedicales.fr › Glucides › Hétérosides › Saponines › Polygala saponins inhibit NLRP3...