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An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine

INTRODUCTION: Neuroinflammation is one of the major pathogeneses in Alzheimer’s disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inef...

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Autores principales: Zhao, Xin, Ge, Pingyuan, Lei, Shaohua, Guo, Siqi, Zhou, Peng, Zhao, Li, Qi, Yiyu, Wei, Xiaotong, Wu, Weizhen, Wang, Ningjing, Guo, Rui, Yang, Nianyun, Xiao, Qingqing, Zhang, Qichun, Zhu, Huaxu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441573/
https://www.ncbi.nlm.nih.gov/pubmed/37609432
http://dx.doi.org/10.2147/DDDT.S417465
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author Zhao, Xin
Ge, Pingyuan
Lei, Shaohua
Guo, Siqi
Zhou, Peng
Zhao, Li
Qi, Yiyu
Wei, Xiaotong
Wu, Weizhen
Wang, Ningjing
Guo, Rui
Yang, Nianyun
Xiao, Qingqing
Zhang, Qichun
Zhu, Huaxu
author_facet Zhao, Xin
Ge, Pingyuan
Lei, Shaohua
Guo, Siqi
Zhou, Peng
Zhao, Li
Qi, Yiyu
Wei, Xiaotong
Wu, Weizhen
Wang, Ningjing
Guo, Rui
Yang, Nianyun
Xiao, Qingqing
Zhang, Qichun
Zhu, Huaxu
author_sort Zhao, Xin
collection PubMed
description INTRODUCTION: Neuroinflammation is one of the major pathogeneses in Alzheimer’s disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD. METHODS: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1β, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of β-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of β-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo. RESULTS: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aβ plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB. CONCLUSION: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells.
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spelling pubmed-104415732023-08-22 An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine Zhao, Xin Ge, Pingyuan Lei, Shaohua Guo, Siqi Zhou, Peng Zhao, Li Qi, Yiyu Wei, Xiaotong Wu, Weizhen Wang, Ningjing Guo, Rui Yang, Nianyun Xiao, Qingqing Zhang, Qichun Zhu, Huaxu Drug Des Devel Ther Original Research INTRODUCTION: Neuroinflammation is one of the major pathogeneses in Alzheimer’s disease (AD) and mainly involves abnormal inflammatory activation of microglia by multiple pathological stimuli. The treatment of AD remains a major challenge due to the multifactorial characterization of AD and the inefficient ability of therapeutic drugs to permeate through the blood‒brain barrier (BBB). Accordingly, drug combination treatment and drug carrier delivery have become important therapeutic tools for the treatment of multifactorial diseases, especially AD. METHODS: Inflammatory cytokine levels in microglia, including NO, TNF-α, IL-1β, IL-4, and IL-10, were detected. The Morris water maze and object location task were used to investigate the learning and memory functions of APP/PS1 mice in different treatment groups. The number of neurons and plasticity of synapses were evaluated by immunofluorescence double labelling. Additionally, the ratio of β-amyloid plaques and the number of activated microglia were evaluated by immunofluorescence staining. The concentrations of β-amyloid plaques and inflammatory factors in the hippocampus were determined by ELISA. Microglia-derived exosomes (Exos) were extracted and purified by size exclusion chromatography. The distribution of exosomes and drugs was investigated in vitro and in vivo. RESULTS: Compared to single drug interventions, the combination of Ber and Pal (Ber/Pal) modulated microglial inflammatory cytokine levels. Ber/Pal promoted the recovery of learning and memory impairment in APP/PS1 mice. Immunofluorescence staining indicated that Ber/Pal restored neurons, inhibited Aβ plaque formation and microglial activation, and regulated the secretion of inflammatory factors. Exos promoted the accumulation of drugs in cells and tissues and improved the targeting of drugs across the BBB. CONCLUSION: Ber/Pal could offer a synergistic and more comprehensive therapeutic effect in AD. Additionally, the microglia-derived Exos-Ber/Pal delivery system promoted the targeting and permeation of drugs into the brain, suggesting a creative strategy for targeting AD therapy by regulating neuroinflammation in microglial cells. Dove 2023-08-17 /pmc/articles/PMC10441573/ /pubmed/37609432 http://dx.doi.org/10.2147/DDDT.S417465 Text en © 2023 Zhao et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhao, Xin
Ge, Pingyuan
Lei, Shaohua
Guo, Siqi
Zhou, Peng
Zhao, Li
Qi, Yiyu
Wei, Xiaotong
Wu, Weizhen
Wang, Ningjing
Guo, Rui
Yang, Nianyun
Xiao, Qingqing
Zhang, Qichun
Zhu, Huaxu
An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine
title An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine
title_full An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine
title_fullStr An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine
title_full_unstemmed An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine
title_short An Exosome-Based Therapeutic Strategy Targeting Neuroinflammation in Alzheimer’s Disease with Berberine and Palmatine
title_sort exosome-based therapeutic strategy targeting neuroinflammation in alzheimer’s disease with berberine and palmatine
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10441573/
https://www.ncbi.nlm.nih.gov/pubmed/37609432
http://dx.doi.org/10.2147/DDDT.S417465
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