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Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro
The AMPK/PGC-1α pathway-mediated mitochondrial dysfunction has been supposed to play a crucial role in pathogenesis of diabetic peripheral neuropathy (DPN). The present study investigated the neuroprotective potential of quercetin, a natural AMPK activator. Streptozotocin (STZ)-induced diabetic rats...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966726/ https://www.ncbi.nlm.nih.gov/pubmed/33746703 http://dx.doi.org/10.3389/fnins.2021.636172 |
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author | Zhang, Qian Song, Wei Zhao, Bingjia Xie, Jun Sun, Qing Shi, Xiaohu Yan, Bin Tian, Guoqing Liang, Xiaochun |
author_facet | Zhang, Qian Song, Wei Zhao, Bingjia Xie, Jun Sun, Qing Shi, Xiaohu Yan, Bin Tian, Guoqing Liang, Xiaochun |
author_sort | Zhang, Qian |
collection | PubMed |
description | The AMPK/PGC-1α pathway-mediated mitochondrial dysfunction has been supposed to play a crucial role in pathogenesis of diabetic peripheral neuropathy (DPN). The present study investigated the neuroprotective potential of quercetin, a natural AMPK activator. Streptozotocin (STZ)-induced diabetic rats that developed DPN phenotype were orally administrated with quercetin (30 and 60 mg/kg per day) for 6 weeks. The morphologic changes in the sciatic nerves (SN), the pathological structure of neurons in dorsal root ganglion (DRG), and the expressions of myelin proteins were assessed. The ATP content and the mitochondrial ultrastructure were measured. Furthermore, key proteins in the AMPK/PGC-1α pathway were determined. As a result, quercetin administration at both doses improved the paw withdrawal threshold, nerve conduction velocity, and the pathologic changes in SN and DRG of DPN rats. The expressions of myelin basic protein and myelin protein zero were also increased by quercetin. The oxidative stress, decreased ATP generation, and morphological changes of mitochondria were corrected by quercetin. In vitro study found that quercetin treatment significantly decreased the high-glucose-induced generation of reactive oxygen species, as well as attenuated the mitochondrial morphologic injuries and oxidative DNA damages of RSC96 cells. Quercetin treatment promoted the expressions of phosphorylated AMPK, PGC-1α, SIRT1, NRF1, and TFAM under hyperglycemic state in vivo and in vitro. This study revealed that the neuroprotective effect of quercetin was mainly related to mitochondrial protection by activation of the AMPK/PGC-1α pathway for the first time and proved quercetin as a potential therapeutic agent in the management of diabetic neuropathy. |
format | Online Article Text |
id | pubmed-7966726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79667262021-03-18 Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro Zhang, Qian Song, Wei Zhao, Bingjia Xie, Jun Sun, Qing Shi, Xiaohu Yan, Bin Tian, Guoqing Liang, Xiaochun Front Neurosci Neuroscience The AMPK/PGC-1α pathway-mediated mitochondrial dysfunction has been supposed to play a crucial role in pathogenesis of diabetic peripheral neuropathy (DPN). The present study investigated the neuroprotective potential of quercetin, a natural AMPK activator. Streptozotocin (STZ)-induced diabetic rats that developed DPN phenotype were orally administrated with quercetin (30 and 60 mg/kg per day) for 6 weeks. The morphologic changes in the sciatic nerves (SN), the pathological structure of neurons in dorsal root ganglion (DRG), and the expressions of myelin proteins were assessed. The ATP content and the mitochondrial ultrastructure were measured. Furthermore, key proteins in the AMPK/PGC-1α pathway were determined. As a result, quercetin administration at both doses improved the paw withdrawal threshold, nerve conduction velocity, and the pathologic changes in SN and DRG of DPN rats. The expressions of myelin basic protein and myelin protein zero were also increased by quercetin. The oxidative stress, decreased ATP generation, and morphological changes of mitochondria were corrected by quercetin. In vitro study found that quercetin treatment significantly decreased the high-glucose-induced generation of reactive oxygen species, as well as attenuated the mitochondrial morphologic injuries and oxidative DNA damages of RSC96 cells. Quercetin treatment promoted the expressions of phosphorylated AMPK, PGC-1α, SIRT1, NRF1, and TFAM under hyperglycemic state in vivo and in vitro. This study revealed that the neuroprotective effect of quercetin was mainly related to mitochondrial protection by activation of the AMPK/PGC-1α pathway for the first time and proved quercetin as a potential therapeutic agent in the management of diabetic neuropathy. Frontiers Media S.A. 2021-03-03 /pmc/articles/PMC7966726/ /pubmed/33746703 http://dx.doi.org/10.3389/fnins.2021.636172 Text en Copyright © 2021 Zhang, Song, Zhao, Xie, Sun, Shi, Yan, Tian and Liang. http://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 | Neuroscience Zhang, Qian Song, Wei Zhao, Bingjia Xie, Jun Sun, Qing Shi, Xiaohu Yan, Bin Tian, Guoqing Liang, Xiaochun Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro |
title | Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro |
title_full | Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro |
title_fullStr | Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro |
title_full_unstemmed | Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro |
title_short | Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro |
title_sort | quercetin attenuates diabetic peripheral neuropathy by correcting mitochondrial abnormality via activation of ampk/pgc-1α pathway in vivo and in vitro |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966726/ https://www.ncbi.nlm.nih.gov/pubmed/33746703 http://dx.doi.org/10.3389/fnins.2021.636172 |
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