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Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity

Alzheimer’s disease (AD) is a neurodegenerative disorder recognized as a global public health priority. Although available treatments temporarily relieve the symptoms, they could not prevent the progression of cognitive decline. Natural compounds have been rich sources for drug discovery. Dendrobium...

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Autores principales: Li, Dai-Di, Fan, Hong-Xia, Yang, Rong, Li, Ying-Ying, Zhang, Feng, Shi, Jing-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108428/
https://www.ncbi.nlm.nih.gov/pubmed/35586062
http://dx.doi.org/10.3389/fphar.2022.846541
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author Li, Dai-Di
Fan, Hong-Xia
Yang, Rong
Li, Ying-Ying
Zhang, Feng
Shi, Jing-Shan
author_facet Li, Dai-Di
Fan, Hong-Xia
Yang, Rong
Li, Ying-Ying
Zhang, Feng
Shi, Jing-Shan
author_sort Li, Dai-Di
collection PubMed
description Alzheimer’s disease (AD) is a neurodegenerative disorder recognized as a global public health priority. Although available treatments temporarily relieve the symptoms, they could not prevent the progression of cognitive decline. Natural compounds have been rich sources for drug discovery. Dendrobium nobile Lindl. alkaloid (DNLA) is the main active compound in Dendrobium nobile Lindl, a traditional Chinese herbal medicine. Recent studies indicated that DNLA produced neuroprotection. However, the mechanisms underlying DNLA-generated neuroprotection remain unknown. To investigate neuroprotection and the underlying mechanisms of DNLA, mouse hippocampus injection of lipopolysaccharide (LPS)-induced neuronal damage was performed. DNLA protected hippocampus neurons and working memory disorder against LPS-induced neurotoxicity. In addition, DNLA suppressed cell undergoing membrane lysis and cell swelling and inhibited the essential mediator of pyroptosis GSDMD-N expressions. Furthermore, DNLA-mediated neuroprotection was dependent on the inhibition of NLRP3 inflammasome activation, as evidenced by the fact that DNLA reduced pro-inflammatory factor (IL-18 and IL-1β) production and inhibited the expression of related proteins. DNLA-exerted neuroprotection against LPS-induced neuronal damage, and cognitive impairment was not observed in NLRP3 knockout mice. Together, this study suggested that DNLA attenuated NLRP3-mediated pyroptosis to generate neuroprotection against LPS-induced neuronal damage and cognitive impairment.
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spelling pubmed-91084282022-05-17 Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity Li, Dai-Di Fan, Hong-Xia Yang, Rong Li, Ying-Ying Zhang, Feng Shi, Jing-Shan Front Pharmacol Pharmacology Alzheimer’s disease (AD) is a neurodegenerative disorder recognized as a global public health priority. Although available treatments temporarily relieve the symptoms, they could not prevent the progression of cognitive decline. Natural compounds have been rich sources for drug discovery. Dendrobium nobile Lindl. alkaloid (DNLA) is the main active compound in Dendrobium nobile Lindl, a traditional Chinese herbal medicine. Recent studies indicated that DNLA produced neuroprotection. However, the mechanisms underlying DNLA-generated neuroprotection remain unknown. To investigate neuroprotection and the underlying mechanisms of DNLA, mouse hippocampus injection of lipopolysaccharide (LPS)-induced neuronal damage was performed. DNLA protected hippocampus neurons and working memory disorder against LPS-induced neurotoxicity. In addition, DNLA suppressed cell undergoing membrane lysis and cell swelling and inhibited the essential mediator of pyroptosis GSDMD-N expressions. Furthermore, DNLA-mediated neuroprotection was dependent on the inhibition of NLRP3 inflammasome activation, as evidenced by the fact that DNLA reduced pro-inflammatory factor (IL-18 and IL-1β) production and inhibited the expression of related proteins. DNLA-exerted neuroprotection against LPS-induced neuronal damage, and cognitive impairment was not observed in NLRP3 knockout mice. Together, this study suggested that DNLA attenuated NLRP3-mediated pyroptosis to generate neuroprotection against LPS-induced neuronal damage and cognitive impairment. Frontiers Media S.A. 2022-05-02 /pmc/articles/PMC9108428/ /pubmed/35586062 http://dx.doi.org/10.3389/fphar.2022.846541 Text en Copyright © 2022 Li, Fan, Yang, Li, Zhang and Shi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Dai-Di
Fan, Hong-Xia
Yang, Rong
Li, Ying-Ying
Zhang, Feng
Shi, Jing-Shan
Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity
title Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity
title_full Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity
title_fullStr Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity
title_full_unstemmed Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity
title_short Dendrobium Nobile Lindl. Alkaloid Suppresses NLRP3-Mediated Pyroptosis to Alleviate LPS-Induced Neurotoxicity
title_sort dendrobium nobile lindl. alkaloid suppresses nlrp3-mediated pyroptosis to alleviate lps-induced neurotoxicity
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108428/
https://www.ncbi.nlm.nih.gov/pubmed/35586062
http://dx.doi.org/10.3389/fphar.2022.846541
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