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...

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Main Authors: Jingyu Wang, Heyangzi Li, Yucheng Ren, Ying Yao, Jue Hu, Mingzhi Zheng, Yuemin Ding, Ying-ying Chen, Yueliang Shen, Lin-lin Wang, Yongjian  Zhu
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
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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.
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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
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