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Ginsenoside Re Promotes Nerve Regeneration by Facilitating the Proliferation, Differentiation and Migration of Schwann Cells via the ERK- and JNK-Dependent Pathway in Rat Model of Sciatic Nerve Crush Injury

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Abstract

Exploring effective drugs that are capable of promoting nerve regeneration has gained much attention. Ginsenoside Re (Re) is the main ingredient of ginseng berries and roots. Research in the area has shown that ginsenoside Re exhibits multiple pharmacological activities via different mechanisms both in vivo and in vitro. But the potential therapeutic effects of Re on sciatic nerve crush injury (SNC) have been little investigated. Herein, we investigated the protect effect of Re on peripheral nerve regeneration in a rat SNC model. Walking track analysis revealed that Re treatment significantly promoted functional recovery of crushed sciatic nerve in rats. The expression of PCNA in rat sciatic nerve was up-regulated by Re treatment, and peaked when the concentration of Re was 2.0 mg/kg. Using immunofluorescent staining, we found that Re greatly increased the expression of GAP-43 and S100 in injured rat sciatic nerve. Furthermore, we evaluated the effects of Re on proliferation, differentiation, and migration of Schwann cells in SNC rat models. Our studies reveal that Re promotes nerve regeneration is depend on ERK1/2 and JNK1/2 signaling pathway. Elevated Oct-6 expression and featured morphological changes indicated that Re facilitated the differentiation of Schwann cells following SNC. Also, transwell and wound-healing assay demonstrated that the migration capabilities of Schwann cell were significantly enhanced after Re treatment.

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Abbreviations

SNC:

Sciatic nerve crush injury

PNI:

Peripheral nerve injury

SFI:

Sciatic functional index

TSI:

Toe spread index

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

SC:

Schwann cell

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Acknowledgments

This work was supported in part by the National Basic Research Program of China (973 Program 2012CB8221004); the National Natural Science Fund (31170766); and the Nantong City Social Development Projects funds (HS2012032); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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    Authors and Affiliations

    1. Nanjing University of Chinese Medicine, Nanjing, 210000, China

      Lei Wang & Qian Tan

    2. Department of Burns and Plastic Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, China

      Lei Wang

    3. Department of Immunology, Medical College, Nantong University, Nantong, 226001, China

      Damin Yuan

    4. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, China

      Dongmei Zhang & Chun Liu

    5. Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, China

      Weidong Zhang

    6. Department of Orthopaedics, Traditional Chinese Medical Hospital of Nantong City, Nantong, 226001, China

      Hongbing Cheng

    7. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, China

      Yan Song

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    1. Lei Wang
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    Correspondence to Qian Tan.

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    Lei Wang and Damin Yuan have contributed equally to this work

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    Wang, L., Yuan, D., Zhang, D. et al. Ginsenoside Re Promotes Nerve Regeneration by Facilitating the Proliferation, Differentiation and Migration of Schwann Cells via the ERK- and JNK-Dependent Pathway in Rat Model of Sciatic Nerve Crush Injury. Cell Mol Neurobiol 35, 827–840 (2015). https://doi.org/10.1007/s10571-015-0177-7

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