Osthole Protects Bone Marrow-Derived Neural Stem Cells from Oxidative Damage through PI3K/Akt-1 Pathway

被引:40
作者
Yan, Yu-hui [1 ]
Li, Shao-heng [1 ]
Li, Hong-yan [1 ]
Lin, Ying [1 ]
Yang, Jing-xian [1 ]
机构
[1] Liaoning Univ Tradit Chinese Med, Sch Pharm, Dalian 116600, Peoples R China
基金
中国国家自然科学基金;
关键词
Osthole; Neural stem cells; Oxidative stress; Apoptosis; Phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt-1) pathway; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; SIGNALING PATHWAY; NEURODEGENERATIVE DISEASES; MITOCHONDRIAL DYSFUNCTION; NEURONAL DIFFERENTIATION; WNT/BETA-CATENIN; RATS; STRESS; HIPPOCAMPUS;
D O I
10.1007/s11064-016-2082-y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In recent years, neural stem cell (NSC) transplantation has been widely explored as a treatment for neurodegenerative diseases. NSCs are special cells that have some capacity for self-renewal and the potential to differentiate into multiple cell types. However, the inflammatory environment of diseased tissue is not conducive to the survival of transplanted cells. Osthole (Ost) is a principal bioactive component of Fructus Cnidii, Radix Angelicae Pubescentis and other traditional Chinese medicines. Ost has a wide range of pharmacological activities, such as anti-inflammation, immunomodulation, and neuroprotection. In the present study, we assessed the protective effects of Ost on bone marrow-derived-NSCs (BM-NSCs) against injury induced by hydrogen peroxide (H2O2). BM-NSCs were pre-treated with different doses of Ost and treated with H2O2. The cell counting kit-8 (CCK-8) method and lactate dehydrogenase (LDH) leakage assay were used to determine cell viability. Using the TUNEL assay and RT-PCR, we evaluated the effect of Ost on cell apoptosis. The results showed that Ost had protective effects against H2O2-induced cell damage, and the number of apoptotic cells was significantly decreased in the Ost pre-treated groups compared to the H2O2 group. The expression ratio of Bax/Bcl-2 mRNA was also decreased. Furthermore, western blotting was used to analyze levels of proteins related to PI3K/Akt-1 signaling pathway, and results indicated that ost can increase p-Akt and PI3K. Our findings suggested that Ost protects BM-NSCs against oxidative stress injury, and it can be used to improve the inflammatory environment of neurodegenerative diseases so and promote the survival rate of transplanted NSCs.
引用
收藏
页码:398 / 405
页数:8
相关论文
共 41 条
[1]  
[Anonymous], MATH PROBLEMS ENG, DOI DOI 10.1016/J.NAN0.2014.03.006
[2]  
[Anonymous], 2014, NANOMEDICINE, DOI DOI 10.1186/2045-3701-4-67
[3]   Oxidative balance, homocysteine, and uric acid levels in older patients with Late Onset Alzheimer's Disease or Vascular Dementia [J].
Cervellati, Carlo ;
Romani, Arianna ;
Seripa, Davide ;
Cremonini, Eleonora ;
Bosi, Cristina ;
Magon, Stefania ;
Passaro, Angelina ;
Bergamini, Carlo M. ;
Pilotto, Alberto ;
Zuliani, Giovanni .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2014, 337 (1-2) :156-161
[4]   Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats [J].
Chao, Xiaodong ;
Zhou, Jun ;
Chen, Tao ;
Liu, Wenbo ;
Dong, Wenpeng ;
Qu, Yan ;
Jiang, Xiaofan ;
Ji, Xituan ;
Zhen, Haining ;
Fei, Zhou .
BRAIN RESEARCH, 2010, 1363 :206-211
[5]   Effect of the plant-extract osthole on the relaxation of rabbit corpus cavernosum tissue in vitro [J].
Chen, J ;
Chiou, WF ;
Chen, CC ;
Chen, CF .
JOURNAL OF UROLOGY, 2000, 163 (06) :1975-1980
[6]   NEUROPROTECTIVE EFFECT OF OSTHOLE AGAINST OXYGEN AND GLUCOSE DEPRIVATION IN RAT CORTICAL NEURONS: INVOLVEMENT OF MITOGEN-ACTIVATED PROTEIN KINASE PATHWAY [J].
Chen, T. ;
Liu, W. ;
Chao, X. ;
Qu, Y. ;
Zhang, L. ;
Luo, P. ;
Xie, K. ;
Huo, J. ;
Fei, Z. .
NEUROSCIENCE, 2011, 183 :203-211
[7]   The BCL2 family: Regulators of the cellular life-or-death switch [J].
Cory, S ;
Adams, JM .
NATURE REVIEWS CANCER, 2002, 2 (09) :647-656
[8]   Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery [J].
Datta, SR ;
Dudek, H ;
Tao, X ;
Masters, S ;
Fu, HA ;
Gotoh, Y ;
Greenberg, ME .
CELL, 1997, 91 (02) :231-241
[9]   Are oxidative stress and mitochondrial dysfunction the key players in the neurodegenerative diseases? [J].
Di Carlo, Marta ;
Giacomazza, Daniela ;
Picone, Pasquale ;
Nuzzo, Domenico ;
San Biagio, Pier Luigi .
FREE RADICAL RESEARCH, 2012, 46 (11) :1327-1338
[10]   Osthole Exhibits Anti-Cancer Property in Rat Glioma Cells Through Inhibiting PI3K/Akt and MAPK Signaling Pathways [J].
Ding, Daofang ;
Wei, Songpu ;
Song, Yi ;
Li, Linghui ;
Du, Guoqing ;
Zhan, Hongsheng ;
Cao, Yuelong .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2013, 32 (06) :1751-1760