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Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease

Rehmanniae Radix (RR, the dried tuberous roots of Rehmannia glutinosa (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-rela...

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Autores principales: Kang, Nianxin, Luan, Yage, Jiang, Yu, Cheng, Wenhao, Liu, Yongjian, Su, Zhijun, Liu, Yonggang, Tan, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247152/
https://www.ncbi.nlm.nih.gov/pubmed/35784741
http://dx.doi.org/10.3389/fphar.2022.878631
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author Kang, Nianxin
Luan, Yage
Jiang, Yu
Cheng, Wenhao
Liu, Yongjian
Su, Zhijun
Liu, Yonggang
Tan, Peng
author_facet Kang, Nianxin
Luan, Yage
Jiang, Yu
Cheng, Wenhao
Liu, Yongjian
Su, Zhijun
Liu, Yonggang
Tan, Peng
author_sort Kang, Nianxin
collection PubMed
description Rehmanniae Radix (RR, the dried tuberous roots of Rehmannia glutinosa (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-related diseases in a class of prescriptions. The oligosaccharides and catalpol in RR have been confirmed to have neuroprotective effects. However, there are few studies on the anti-Alzheimer’s disease (AD) effect of oligosaccharides in Rehmanniae Radix (ORR). The chemical components and pharmacological effects of dried Rehmannia Radix (DRR) and prepared Rehmannia Radix (PRR) are different because of the different processing methods. ORR has neuroprotective potential, such as improving learning and memory in rats. Therefore, this study aimed to prove the importance of oligosaccharides in DRR (ODRR) and PRR (OPRR) for AD based on the Caenorhabditis elegans (C. elegans) model and the different roles of ODRR and OPRR in the treatment of AD. In this study, we used paralysis assays, lifespan and stress resistance assays, bacterial growth curve, developmental and behavioral parameters, and ability of learning and memory to explore the effects of ODRR and OPRR on anti-AD and anti-aging. Furthermore, the accumulation of reactive oxygen species (ROS); deposition of Aβ; and expression of amy-1, sir-2.1, daf-16, sod-3, skn-1, and hsp-16.2 were analyzed to confirm the efficacy of ODRR and OPRR. OPRR was more effective than ODRR in delaying the paralysis, improving learning ability, and prolonging the lifespan of C. elegans. Further mechanism studies showed that the accumulation of ROS, aggregation, and toxicity of Aβ were reduced, suggesting that ORR alleviated Aβ-induced toxicity, in part, through antioxidant activity and Aβ aggregation inhibiting. The expression of amy-1 was downregulated, and sir-2.1, daf-16, sod-3, and hsp-16.2 were upregulated. Thus, ORR could have a possible therapeutic effect on AD by modulating the expression of amy-1, sir-2.1, daf-16, sod-3, and hsp-16.2. Furthermore, ORR promoted the nuclear localization of daf-16 and further increased the expression of sod-3 and hsp-16.2, which significantly contributed to inhibiting the Aβ toxicity and enhancing oxidative stress resistance. In summary, the study provided a new idea for the development of ORR.
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spelling pubmed-92471522022-07-02 Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease Kang, Nianxin Luan, Yage Jiang, Yu Cheng, Wenhao Liu, Yongjian Su, Zhijun Liu, Yonggang Tan, Peng Front Pharmacol Pharmacology Rehmanniae Radix (RR, the dried tuberous roots of Rehmannia glutinosa (Gaertn.) DC.) is an important traditional Chinese medicine distributed in Henan, Hebei, Inner Mongolia, and Northeast in China. RR is frequently used to treat diabetes mellitus, cardiovascular disease, osteoporosis and aging-related diseases in a class of prescriptions. The oligosaccharides and catalpol in RR have been confirmed to have neuroprotective effects. However, there are few studies on the anti-Alzheimer’s disease (AD) effect of oligosaccharides in Rehmanniae Radix (ORR). The chemical components and pharmacological effects of dried Rehmannia Radix (DRR) and prepared Rehmannia Radix (PRR) are different because of the different processing methods. ORR has neuroprotective potential, such as improving learning and memory in rats. Therefore, this study aimed to prove the importance of oligosaccharides in DRR (ODRR) and PRR (OPRR) for AD based on the Caenorhabditis elegans (C. elegans) model and the different roles of ODRR and OPRR in the treatment of AD. In this study, we used paralysis assays, lifespan and stress resistance assays, bacterial growth curve, developmental and behavioral parameters, and ability of learning and memory to explore the effects of ODRR and OPRR on anti-AD and anti-aging. Furthermore, the accumulation of reactive oxygen species (ROS); deposition of Aβ; and expression of amy-1, sir-2.1, daf-16, sod-3, skn-1, and hsp-16.2 were analyzed to confirm the efficacy of ODRR and OPRR. OPRR was more effective than ODRR in delaying the paralysis, improving learning ability, and prolonging the lifespan of C. elegans. Further mechanism studies showed that the accumulation of ROS, aggregation, and toxicity of Aβ were reduced, suggesting that ORR alleviated Aβ-induced toxicity, in part, through antioxidant activity and Aβ aggregation inhibiting. The expression of amy-1 was downregulated, and sir-2.1, daf-16, sod-3, and hsp-16.2 were upregulated. Thus, ORR could have a possible therapeutic effect on AD by modulating the expression of amy-1, sir-2.1, daf-16, sod-3, and hsp-16.2. Furthermore, ORR promoted the nuclear localization of daf-16 and further increased the expression of sod-3 and hsp-16.2, which significantly contributed to inhibiting the Aβ toxicity and enhancing oxidative stress resistance. In summary, the study provided a new idea for the development of ORR. Frontiers Media S.A. 2022-06-17 /pmc/articles/PMC9247152/ /pubmed/35784741 http://dx.doi.org/10.3389/fphar.2022.878631 Text en Copyright © 2022 Kang, Luan, Jiang, Cheng, Liu, Su, Liu and Tan. 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
Kang, Nianxin
Luan, Yage
Jiang, Yu
Cheng, Wenhao
Liu, Yongjian
Su, Zhijun
Liu, Yonggang
Tan, Peng
Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease
title Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease
title_full Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease
title_fullStr Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease
title_full_unstemmed Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease
title_short Neuroprotective Effects of Oligosaccharides in Rehmanniae Radix on Transgenic Caenorhabditis elegans Models for Alzheimer’s Disease
title_sort neuroprotective effects of oligosaccharides in rehmanniae radix on transgenic caenorhabditis elegans models for alzheimer’s disease
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247152/
https://www.ncbi.nlm.nih.gov/pubmed/35784741
http://dx.doi.org/10.3389/fphar.2022.878631
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