Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury
Background/Aims: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract β-elemene in vitro and in a rat model of SCI. Methods: CCK-8 assay was used to evaluate...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Cell Physiol Biochem Press GmbH & Co KG
2018-08-01
|
Series: | Cellular Physiology and Biochemistry |
Subjects: | |
Online Access: | https://www.karger.com/Article/FullText/492996 |
_version_ | 1818539906088042496 |
---|---|
author | Jingyu Wang Heyangzi Li Yucheng Ren Ying Yao Jue Hu Mingzhi Zheng Yuemin Ding Ying-ying Chen Yueliang Shen Lin-lin Wang Yongjian Zhu |
author_facet | Jingyu Wang Heyangzi Li Yucheng Ren Ying Yao Jue Hu Mingzhi Zheng Yuemin Ding Ying-ying Chen Yueliang Shen Lin-lin Wang Yongjian Zhu |
author_sort | Jingyu Wang |
collection | DOAJ |
description | Background/Aims: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract β-elemene in vitro and in a rat model of SCI. Methods: CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen’s method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression. Results: β-elemene (20 μg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. β-elemene reduced CoCl2-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that β-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that β-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, β-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1β. Conclusion: β-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, β-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of β-elemene in SCI patients. |
first_indexed | 2024-12-11T21:48:18Z |
format | Article |
id | doaj.art-e2a2f35ab27646898458c9ca149e00b0 |
institution | Directory Open Access Journal |
issn | 1015-8987 1421-9778 |
language | English |
last_indexed | 2024-12-11T21:48:18Z |
publishDate | 2018-08-01 |
publisher | Cell Physiol Biochem Press GmbH & Co KG |
record_format | Article |
series | Cellular Physiology and Biochemistry |
spelling | doaj.art-e2a2f35ab27646898458c9ca149e00b02022-12-22T00:49:32ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-08-0149259560910.1159/000492996492996Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord InjuryJingyu WangHeyangzi LiYucheng RenYing YaoJue HuMingzhi ZhengYuemin DingYing-ying ChenYueliang ShenLin-lin WangYongjian ZhuBackground/Aims: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract β-elemene in vitro and in a rat model of SCI. Methods: CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen’s method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression. Results: β-elemene (20 μg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. β-elemene reduced CoCl2-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that β-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that β-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, β-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1β. Conclusion: β-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, β-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of β-elemene in SCI patients.https://www.karger.com/Article/FullText/492996β-elemeneSpinal cord injuryMotor neuronsER stressApoptosis |
spellingShingle | Jingyu Wang Heyangzi Li Yucheng Ren Ying Yao Jue Hu Mingzhi Zheng Yuemin Ding Ying-ying Chen Yueliang Shen Lin-lin Wang Yongjian Zhu Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury Cellular Physiology and Biochemistry β-elemene Spinal cord injury Motor neurons ER stress Apoptosis |
title | Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury |
title_full | Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury |
title_fullStr | Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury |
title_full_unstemmed | Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury |
title_short | Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury |
title_sort | local delivery of β elemene improves locomotor functional recovery by alleviating endoplasmic reticulum stress and reducing neuronal apoptosis in rats with spinal cord injury |
topic | β-elemene Spinal cord injury Motor neurons ER stress Apoptosis |
url | https://www.karger.com/Article/FullText/492996 |
work_keys_str_mv | AT jingyuwang localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT heyangzili localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT yuchengren localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT yingyao localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT juehu localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT mingzhizheng localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT yueminding localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT yingyingchen localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT yueliangshen localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT linlinwang localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury AT yongjianzhu localdeliveryofbelemeneimproveslocomotorfunctionalrecoverybyalleviatingendoplasmicreticulumstressandreducingneuronalapoptosisinratswithspinalcordinjury |