Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway

Objective: Despite the potential therapeutic approaches of bone marrow-derived mesenchymal stem cells (BMSCs) in orthopaedic, their applications are hampered by harsh oxidative stress conditions after transplantation. In this study, the anti- apoptotic and anti-oxidative properties of lithospermic a...

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Main Authors: Li Wang-Yang, Zhou You-Liang, Li Tiao, Zeng Peng, Xu Wu-Ji, Lu Xiao-Long, Qi Xin-Yu, Xiong Hui
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2019-03-01
Series:Digital Chinese Medicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2589377719300795
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author Li Wang-Yang
Zhou You-Liang
Li Tiao
Zeng Peng
Xu Wu-Ji
Lu Xiao-Long
Qi Xin-Yu
Xiong Hui
author_facet Li Wang-Yang
Zhou You-Liang
Li Tiao
Zeng Peng
Xu Wu-Ji
Lu Xiao-Long
Qi Xin-Yu
Xiong Hui
author_sort Li Wang-Yang
collection DOAJ
description Objective: Despite the potential therapeutic approaches of bone marrow-derived mesenchymal stem cells (BMSCs) in orthopaedic, their applications are hampered by harsh oxidative stress conditions after transplantation. In this study, the anti- apoptotic and anti-oxidative properties of lithospermic acid (LSA) on BMSCs exposed to hydrogen peroxide (H2O2) were investigated. Methods: In the present study, we used H2O2 to induce oxidative injury on BMSCs. Reactive oxygen species (ROS) staining and superoxide dismutase (SOD) assay were performed. The expression levels of phosphorylated (p)-Akt, Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) were measured by Western blotting. Results: LSA can significantly reduce H2O2-induced chromatin condensation and intracellular ROS levels, enhance the activity of SOD. Moreover, it can alleviate H2O2-induced apoptosis by up- regulating Bcl-2 and p-Akt, down-regulating Bax, which was blocked by the PI3K inhibitor, LY294002. Conclusions: Our results demonstrated that pretreatment with LSA could attenuate oxidative stress-induced apoptosis in BMSCs, which may be related with anti-oxidant properties and partly via modulating PI3K/Akt pathway, suggesting that pharmacologically manipulating BMSCs with LSA could be a promising drug to increase cell survival for BMSCs transplantation in musculoskeletal disorders of orthopaedic. Keywords: Oxidative stress, Lithospermic acid, Apoptosis, BMSCs, PI3K/Akt
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spelling doaj.art-6a40d78dd3d245ff8c7059fc2580dca92022-12-22T01:54:38ZengKeAi Communications Co., Ltd.Digital Chinese Medicine2589-37772019-03-01212940Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt PathwayLi Wang-Yang0Zhou You-Liang1Li Tiao2Zeng Peng3Xu Wu-Ji4Lu Xiao-Long5Qi Xin-Yu6Xiong Hui7Hunan University of Chinese Medicine, Changsha, Hunan, 410208, ChinaThe First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, ChinaThe Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, ChinaThe Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410005, ChinaThe Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410005, ChinaThe Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410005, ChinaHunan University of Chinese Medicine, Changsha, Hunan, 410208, ChinaHunan University of Chinese Medicine, Changsha, Hunan, 410208, China; Corresponding author. Research direction: orthopedics &traumatology of Chinese medicine. .Objective: Despite the potential therapeutic approaches of bone marrow-derived mesenchymal stem cells (BMSCs) in orthopaedic, their applications are hampered by harsh oxidative stress conditions after transplantation. In this study, the anti- apoptotic and anti-oxidative properties of lithospermic acid (LSA) on BMSCs exposed to hydrogen peroxide (H2O2) were investigated. Methods: In the present study, we used H2O2 to induce oxidative injury on BMSCs. Reactive oxygen species (ROS) staining and superoxide dismutase (SOD) assay were performed. The expression levels of phosphorylated (p)-Akt, Bcl-2-associated X protein (Bax) and B-cell lymphoma 2 (Bcl-2) were measured by Western blotting. Results: LSA can significantly reduce H2O2-induced chromatin condensation and intracellular ROS levels, enhance the activity of SOD. Moreover, it can alleviate H2O2-induced apoptosis by up- regulating Bcl-2 and p-Akt, down-regulating Bax, which was blocked by the PI3K inhibitor, LY294002. Conclusions: Our results demonstrated that pretreatment with LSA could attenuate oxidative stress-induced apoptosis in BMSCs, which may be related with anti-oxidant properties and partly via modulating PI3K/Akt pathway, suggesting that pharmacologically manipulating BMSCs with LSA could be a promising drug to increase cell survival for BMSCs transplantation in musculoskeletal disorders of orthopaedic. Keywords: Oxidative stress, Lithospermic acid, Apoptosis, BMSCs, PI3K/Akthttp://www.sciencedirect.com/science/article/pii/S2589377719300795
spellingShingle Li Wang-Yang
Zhou You-Liang
Li Tiao
Zeng Peng
Xu Wu-Ji
Lu Xiao-Long
Qi Xin-Yu
Xiong Hui
Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway
Digital Chinese Medicine
title Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway
title_full Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway
title_fullStr Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway
title_full_unstemmed Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway
title_short Pretreatment with Lithospermic Acid Attenuates Oxidative Stress- induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway
title_sort pretreatment with lithospermic acid attenuates oxidative stress induced apoptosis in bone marrow derived mesenchymal stem cells via anti oxidation and activation of pi3k akt pathway
url http://www.sciencedirect.com/science/article/pii/S2589377719300795
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