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Ninjin’yoeito and ginseng extract prevent oxaliplatin-induced neurodegeneration in PC12 cells

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Abstract

Ninjin’yoeito (NYT) is a formula of Japanese traditional kampo medicine composed of 12 crude drugs, and is designed to improve the decline in constitution after recovery from disease, fatigue, anemia, anorexia, perspiration during sleep, cold limbs, slight fever, chills, persistent cough, malaise, mental disequilibrium, insomnia, and constipation. Oxaliplatin (L-OHP) is a platinum-based anticancer drug used to treat colorectal, pancreatic, and stomach cancers. However, it often causes acute and chronic peripheral neuropathies including cold allodynia and mechanical hyperalgesia. In this study, we investigated the preventive effects of NYT on neuronal degeneration caused by L-OHP using PC12 cells, which are derived from the rat adrenal medulla and differentiate into nerve-like cells after exposure to nerve growth factor. L-OHP treatment decreased the elongation of neurite-like projection outgrowths in differentiated PC12 cells. When PC12 cells were treated with NYT hot water extract, neurodegeneration caused by L-OHP was significantly prevented in a concentration-dependent manner. Among the 12 crude drugs composing NYT, the extract of Ginseng (the root of Panax ginseng) exhibited the strongest preventive effects on neurodegeneration in differentiated PC12 cells. By activity-guided fractionation, we found that the fraction containing ginsenosides displayed preventive activity and, among several ginsenosides, ginsenoside F2 exhibited significant preventive effects on L-OHP-induced decreases in neurite-like outgrowths in differentiated PC12 cells. These results suggest that NYT and ginseng are promising agents for preventing L-OHP-induced neuropathies and present ginsenoside F2 as one of the active ingredients in ginseng.

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Acknowledgments

This research was supported by Grants-in-Aid for Scientific Research (KAKENHI) C, # 22590669 (2010) and by Research Foundation for Oriental Medicine (2012).

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Author notes

  1. Toshiaki Suzuki

    Present address: Department of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, 464-8601, Japan

  2. Hajime Mizukami

    Present address: The Kochi Prefectural Makino Botanical Garden, Kochi, 781-8125, Japan

Authors and Affiliations

  1. Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan

    Toshiaki Suzuki, Ayano Yamamoto, Hajime Mizukami & Toshiaki Makino

  2. Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan

    Masahiro Ohsawa

  3. Department of Medical Oncology, Kanazawa Medical University, Uchinada, Ishikawa, 920-0293, Japan

    Yoshiharu Motoo

Authors
  1. Toshiaki Suzuki
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  2. Ayano Yamamoto
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  3. Masahiro Ohsawa
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  4. Yoshiharu Motoo
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  5. Hajime Mizukami
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  6. Toshiaki Makino
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Correspondence to Toshiaki Makino.

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Suzuki, T., Yamamoto, A., Ohsawa, M. et al. Ninjin’yoeito and ginseng extract prevent oxaliplatin-induced neurodegeneration in PC12 cells. J Nat Med 69, 531–537 (2015). https://doi.org/10.1007/s11418-015-0921-9

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  • DOI: https://doi.org/10.1007/s11418-015-0921-9

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