The Kampo medicine Yokukansan (YKS) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells

Authors

  • Kazuki Terada Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan http://orcid.org/0000-0003-0257-5812
  • Yukari Matsushima Laboratory of Pharmacology, Department of Pharmacy, Graduate School of Pharmacy, Yasuda Women’s University, Hiroshima, Japan; Center for Pharmaceutical Education, Yokohama University of Pharmacy, Kanagawa, Japan
  • Kazuhisa Matsunaga Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
  • Jiro Takata Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
  • Yoshiharu Karube Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
  • Atsushi Ishige Laboratory of Kampo Pharmacology, Yokohama University of Pharmacy, Kanagawa, Japan
  • Koji Chiba Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Kanagawa, Japan

DOI:

https://doi.org/10.17305/bjbms.2017.2248

Keywords:

NGF, neurite outgrowth, Kampo, Yokukansan, Akt, ERK1/2, PC12 cells, YKS, TrkA inhibitor, nerve growth factor

Abstract

Accumulating evidence indicates that neurotrophic factor-like substances involved in the induction of neurotrophic factor synthesis may aid in the treatment of neurological disorders, such as Alzheimer’s disease. Yokukansan (YKS), a traditional Kampo medicine, has been used for the treatment of anxiety and mood disorders. In the present study, we aimed to identify the signaling pathways associated with YKS-mediated enhancement of nerve growth factor (NGF)-induced neurite extension in rat pheochromocytoma (PC12) cells. Akt and extracellular-regulated kinase 1/2 (ERK1/2) phosphorylation levels were assessed by western blot analysis, in the presence of YKS and following the treatment with TrkA inhibitor, K252a. YKS treatment (NGF+YKS 0.5 group) enhanced NGF-induced neurite outgrowth and phosphorylation/activation of Akt and ERK1/2 in PC12 cells. Moreover, YKS-induced effects were inhibited by the treatment with the TrkA receptor antagonist K252a (NGF+YKS 0.5+K252a group); no significant difference in neurite outgrowth was observed between K252a-treated (NGF+YKS 0.5+K252a group) and NGF-K252a-treated cells (NGF+K252a group). However, neurite outgrowth in K252a-treated cells (NGF+K252a and NGF+YKS 0.5+K252a group) reached only one-third of the level in NGF-treated cells (NGF group). NGF-mediated Akt phosphorylation increased by YKS was also inhibited by K252a treatment (NGF+YKS 0.5+K252a group), but no significant difference in ERK1/2 phosphorylation was observed between NGF-YKS-K252a- and NGF-treated cells (NGF group). Our results indicate that YKS treatment enhanced NGF-induced neurite outgrowth via induction of Akt and ERK1/2 phosphorylation, following the binding of NGF to the TrkA receptor. These findings may be useful in the development of novel therapeutic strategies for the treatment of Alzheimer’s disease.

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Author Biographies

  • Kazuki Terada, Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
    Laboratory of Drug Design and Drug Delivery
  • Yukari Matsushima, Laboratory of Pharmacology, Department of Pharmacy, Graduate School of Pharmacy, Yasuda Women’s University, Hiroshima, Japan; Center for Pharmaceutical Education, Yokohama University of Pharmacy, Kanagawa, Japan
    Laboratory of Pharmacology, Department of Pharmacy
  • Kazuhisa Matsunaga, Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
    Laboratory of Drug Design and Drug Delivery
  • Jiro Takata, Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
    Laboratory of Drug Design and Drug Delivery
  • Yoshiharu Karube, Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
    Laboratory of Drug Design and Drug Delivery
  • Atsushi Ishige, Laboratory of Kampo Pharmacology, Yokohama University of Pharmacy, Kanagawa, Japan
    Laboratory of Kampo Pharmacology
  • Koji Chiba, Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Kanagawa, Japan
    Laboratory of Clinical Pharmacology

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https://doi.org/10.1111/j.1750-3639.2010.00397.x.

The Kampo medicine Yokukansan (YKS) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells

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01-08-2018

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The Kampo medicine Yokukansan (YKS) enhances nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Biomol Biomed [Internet]. 2018 Aug. 1 [cited 2024 Dec. 6];18(3):224-33. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/2248