Cargando…
Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics
The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. C(max) and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, d...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796108/ https://www.ncbi.nlm.nih.gov/pubmed/29342911 http://dx.doi.org/10.3390/ijms19010159 |
_version_ | 1783297434805338112 |
---|---|
author | Zhou, Yingyu Cheng, Cuilin Baranenko, Denis Wang, Jiaping Li, Yongzhi Lu, Weihong |
author_facet | Zhou, Yingyu Cheng, Cuilin Baranenko, Denis Wang, Jiaping Li, Yongzhi Lu, Weihong |
author_sort | Zhou, Yingyu |
collection | PubMed |
description | The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. C(max) and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters—AUC, MRT, and t(1/2) of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract’s protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC) of mouse brain included tubulin protein family (α-, β-tubulin subunits), dihydropyrimidinase-related protein 2 (CRMP2), γ-actin, 14-3-3 protein family (14-3-3ζ, ε), heat shock protein 90β (HSP90β), and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells’ structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could be effective through the blood–brain barrier in the future. |
format | Online Article Text |
id | pubmed-5796108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57961082018-02-09 Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics Zhou, Yingyu Cheng, Cuilin Baranenko, Denis Wang, Jiaping Li, Yongzhi Lu, Weihong Int J Mol Sci Article The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. C(max) and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters—AUC, MRT, and t(1/2) of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract’s protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC) of mouse brain included tubulin protein family (α-, β-tubulin subunits), dihydropyrimidinase-related protein 2 (CRMP2), γ-actin, 14-3-3 protein family (14-3-3ζ, ε), heat shock protein 90β (HSP90β), and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells’ structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could be effective through the blood–brain barrier in the future. MDPI 2018-01-15 /pmc/articles/PMC5796108/ /pubmed/29342911 http://dx.doi.org/10.3390/ijms19010159 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhou, Yingyu Cheng, Cuilin Baranenko, Denis Wang, Jiaping Li, Yongzhi Lu, Weihong Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics |
title | Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics |
title_full | Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics |
title_fullStr | Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics |
title_full_unstemmed | Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics |
title_short | Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics |
title_sort | effects of acanthopanax senticosus on brain injury induced by simulated spatial radiation in mouse model based on pharmacokinetics and comparative proteomics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796108/ https://www.ncbi.nlm.nih.gov/pubmed/29342911 http://dx.doi.org/10.3390/ijms19010159 |
work_keys_str_mv | AT zhouyingyu effectsofacanthopanaxsenticosusonbraininjuryinducedbysimulatedspatialradiationinmousemodelbasedonpharmacokineticsandcomparativeproteomics AT chengcuilin effectsofacanthopanaxsenticosusonbraininjuryinducedbysimulatedspatialradiationinmousemodelbasedonpharmacokineticsandcomparativeproteomics AT baranenkodenis effectsofacanthopanaxsenticosusonbraininjuryinducedbysimulatedspatialradiationinmousemodelbasedonpharmacokineticsandcomparativeproteomics AT wangjiaping effectsofacanthopanaxsenticosusonbraininjuryinducedbysimulatedspatialradiationinmousemodelbasedonpharmacokineticsandcomparativeproteomics AT liyongzhi effectsofacanthopanaxsenticosusonbraininjuryinducedbysimulatedspatialradiationinmousemodelbasedonpharmacokineticsandcomparativeproteomics AT luweihong effectsofacanthopanaxsenticosusonbraininjuryinducedbysimulatedspatialradiationinmousemodelbasedonpharmacokineticsandcomparativeproteomics |