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Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo

BACKGROUND: Treatment for neuropathic pain as a refractory disease remains unsatisfactory and represents a significant clinical challenge. A highly effective drug is thus urgently needed for neuropathic pain treatment. Dihydromyricetin (DMY) is a flavonoid with a wide range of biological activities....

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Autores principales: Zhang, Wei, Yang, Lingxiao, Li, Longyun, Feng, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576025/
https://www.ncbi.nlm.nih.gov/pubmed/33241000
http://dx.doi.org/10.21037/atm-20-5838
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author Zhang, Wei
Yang, Lingxiao
Li, Longyun
Feng, Wei
author_facet Zhang, Wei
Yang, Lingxiao
Li, Longyun
Feng, Wei
author_sort Zhang, Wei
collection PubMed
description BACKGROUND: Treatment for neuropathic pain as a refractory disease remains unsatisfactory and represents a significant clinical challenge. A highly effective drug is thus urgently needed for neuropathic pain treatment. Dihydromyricetin (DMY) is a flavonoid with a wide range of biological activities. The purpose of this research is to explore the effects of DMY on neuropathic pain and the underlying mechanism of its effect. METHODS: The effect of DMY was investigated in BV-2 cells and lipopolysaccharide (LPS)-induced BV-2 cells. A neuropathic pain model was established via spared nerve injury (SNI) surgery in mice, and the protein expression level was detected via Western blot assay. The percent of M1 and M2 phenotype polarization cells were detected via flow cytometry assay. Immunochemical staining assay was also performed to measure the marker levels of the M1 and M2 phenotype polarization cells and aldehyde dehydrogenase 2 (ALDH2) level, and mechanical pain sensitivity was evaluated via measurement of the mechanical withdrawal threshold. RESULTS: We found that DMY promoted the transition from M1 to M2 polarization and upregulated the ALDH2 level in vitro and vitro. ALDA-1, an ALDH2 agonist, promoted the switching from M1 to M2 polarization in vivo and vitro. DMY alleviated pain hypersensitivity induced by SNI via enhancing M2 phenotype polarization by elevating ALDH2 activity in mice. After DMY- or ALDA-1-microglia were injected into SNI-induced pain hypersensitive mice, the mechanical withdrawal threshold was increased significantly when compared with the SNI group. CONCLUSIONS: Our data demonstrated that DMY alleviated neuropathic pain via enhancing the polarization transition from the M1 to M2 phenotype by potentially elevating ALDH2 activity in vitro and vivo. DMY- or ALDA-1-microglia may have alleviative effects on neuropathic pain. The findings herein provide a promising avenue for neuropathic pain treatment, suggesting a new target, ALDH2, in the treatment of neuropathic pain.
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spelling pubmed-75760252020-11-24 Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo Zhang, Wei Yang, Lingxiao Li, Longyun Feng, Wei Ann Transl Med Original Article BACKGROUND: Treatment for neuropathic pain as a refractory disease remains unsatisfactory and represents a significant clinical challenge. A highly effective drug is thus urgently needed for neuropathic pain treatment. Dihydromyricetin (DMY) is a flavonoid with a wide range of biological activities. The purpose of this research is to explore the effects of DMY on neuropathic pain and the underlying mechanism of its effect. METHODS: The effect of DMY was investigated in BV-2 cells and lipopolysaccharide (LPS)-induced BV-2 cells. A neuropathic pain model was established via spared nerve injury (SNI) surgery in mice, and the protein expression level was detected via Western blot assay. The percent of M1 and M2 phenotype polarization cells were detected via flow cytometry assay. Immunochemical staining assay was also performed to measure the marker levels of the M1 and M2 phenotype polarization cells and aldehyde dehydrogenase 2 (ALDH2) level, and mechanical pain sensitivity was evaluated via measurement of the mechanical withdrawal threshold. RESULTS: We found that DMY promoted the transition from M1 to M2 polarization and upregulated the ALDH2 level in vitro and vitro. ALDA-1, an ALDH2 agonist, promoted the switching from M1 to M2 polarization in vivo and vitro. DMY alleviated pain hypersensitivity induced by SNI via enhancing M2 phenotype polarization by elevating ALDH2 activity in mice. After DMY- or ALDA-1-microglia were injected into SNI-induced pain hypersensitive mice, the mechanical withdrawal threshold was increased significantly when compared with the SNI group. CONCLUSIONS: Our data demonstrated that DMY alleviated neuropathic pain via enhancing the polarization transition from the M1 to M2 phenotype by potentially elevating ALDH2 activity in vitro and vivo. DMY- or ALDA-1-microglia may have alleviative effects on neuropathic pain. The findings herein provide a promising avenue for neuropathic pain treatment, suggesting a new target, ALDH2, in the treatment of neuropathic pain. AME Publishing Company 2020-09 /pmc/articles/PMC7576025/ /pubmed/33241000 http://dx.doi.org/10.21037/atm-20-5838 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zhang, Wei
Yang, Lingxiao
Li, Longyun
Feng, Wei
Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo
title Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo
title_full Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo
title_fullStr Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo
title_full_unstemmed Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo
title_short Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo
title_sort dihydromyricetin attenuates neuropathic pain via enhancing the transition from m1 to m2 phenotype polarization by potentially elevating aldh2 activity in vitro and vivo
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576025/
https://www.ncbi.nlm.nih.gov/pubmed/33241000
http://dx.doi.org/10.21037/atm-20-5838
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