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

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Abstract

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.

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Acknowledgments

The funding was provided by National Natural Science Foundation of China (Grant No. 81173580), Natural Science Foundation of Liaoning Province (Grant Nos. 201102144, 2013225086), Liaoning Province Excellent Talents Project (5th group, No. 191).

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Authors and Affiliations

  1. School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China

    Yu-hui Yan, Shao-heng Li, Hong-yan Li, Ying Lin & Jing-xian Yang

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  2. Shao-heng Li
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Correspondence to Jing-xian Yang.

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Fig. S1 The Chemical Structure of Osthole (DOC 94 KB)

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Yan, Yh., Li, Sh., Li, Hy. et al. Osthole Protects Bone Marrow-Derived Neural Stem Cells from Oxidative Damage through PI3K/Akt-1 Pathway. Neurochem Res 42, 398–405 (2017). https://doi.org/10.1007/s11064-016-2082-y

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