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Protective Effects and Mechanisms of Salvianolic Acid B Against H2O2-Induced Injury in Induced Pluripotent Stem Cell-Derived Neural Stem Cells

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Abstract

Induced pluripotent stem cells (iPSCs) have the potential to differentiate into neural lineages. Salvianolic acid B (Sal B) is a commonly used, traditional Chinese medicine for enhancing neuroprotective effects, and has antioxidant, anti-inflammatory, and antiapoptotic properties. Here, we explore the potential mechanism of Sal B in protecting iPSC-derived neural stem cells (NSCs) against H2O2-induced injury. iPSCs were induced into NSCs, iPSC-derived NSCs were treated with 50 μM Sal B for 24.5 h and 500 μM H2O2 for 24 h. The resulting effects were examined by flow cytometry analysis, quantitative reverse-transcription polymerase chain reaction, and western blotting. Upon H2O2 exposure, Sal B significantly promoted cell viability and stabilization of the mitochondrial membrane potential. Sal B also visibly decreased the cell apoptotic ratio. In addition, Sal B markedly reduced expression of matrix metalloproteinase (MMP)-2 and -9, and phosphospecific signal transducer and activator of transcription 3 (p-STAT3), and increased the level of tissue inhibitor of metalloproteinase (TIMP)-2 in iPSC-derived NSCs induced by H2O2. These results suggest that Sal B protects iPSC-derived NSCs against H2O2-induced oxidative stress. The mechanisms of this stress tolerance may be attributed to modulation of the MMP/TIMP system and inhibition of the STAT3 signaling pathway.

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Acknowledgments

This study was supported by the Natural Science Foundation of China (31170947), the China Postdoctoral Science Foundation (2014M552272), the Guangdong Natural Sciences Foundation of China (S2012020011099 and S2013010016413), the Guangzhou Science and Technology Project of China (2013J4100062), and the New Teachers’ Fund for Doctor Stations of Ministry of Education of China (20100171120088).

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    Authors and Affiliations

    1. Department of Spine Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong, China

      Tao Shu, Mao Pang, Limin Rong, Chang Liu, Wei Zhou, Xuan Wang & Bin Liu

    2. Department of Gynaecology, Baiyun Women’s and Children’s Hospital, Guangzhou, 510000, Guangdong, China

      Juan Wang

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    1. Tao Shu
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    Correspondence to Limin Rong.

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    Tao Shu and Mao Pang have contributed equally to this work.

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    Shu, T., Pang, M., Rong, L. et al. Protective Effects and Mechanisms of Salvianolic Acid B Against H2O2-Induced Injury in Induced Pluripotent Stem Cell-Derived Neural Stem Cells. Neurochem Res 40, 1133–1143 (2015). https://doi.org/10.1007/s11064-015-1573-6

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