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Search of anti-allodynic compounds from Plantaginis Semen, a crude drug ingredient of Kampo formula “Goshajinkigan”

  • Kazufumi ToumeEmail author
  • Zhiyan Hou
  • Huanhuan Yu
  • Mitsuru Kato
  • Miki Maesaka
  • Yanjing Bai
  • Shiho Hanazawa
  • Yuewei Ge
  • Tsugunobu Andoh
  • Katsuko KomatsuEmail author
Original Paper
  • 20 Downloads

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-limiting side effects of cancer chemotherapy. Although the control of CIPN is important, it is difficult to manage with currently available therapeutic drugs. Therefore, there is a need for novel therapeutic agents for treating CIPN. Goshajinkigan (GJG) is a Kampo formula composed of ten crude drugs. While GJG has been used for the treatment of CIPN, the active constituents of GJG and their underlying mechanisms of pharmacological effects are still unknown. Our previous study revealed that repetitive oral administration of the water extract of Plantaginis Semen, a crude drug ingredient of GJG, inhibited the mechanical allodynia induced by an intraperitoneal injection of paclitaxel in mice. To elucidate the active compounds of Plantaginis Semen, activity-guided separation of the water extract of Plantaginis Semen was performed. From the active fraction, four iridoids (14) were identified. Repetitive oral administration of aucubin (1) at 100 or 30 mg/kg and 100 mg/kg of the fraction crude 3 [primarily comprised of pedicularis-lactone (3)], showed anti-allodynic activity, suggesting 1 and 3 could be some of the active compounds responsible for the anti-allodynic property of Plantaginis Semen and GJG. Our study establishes that oral administration of 1 has potent anti-allodynic effect in addition to the activity of intraperitoneally administered 1 reported previously. Identification of active anti-allodynic compounds found in Kampo formulations will support the development of novel therapies for the management of CIPN in cancer patients.

Keywords

Plantaginis Semen Plantago asiatica Allodynia Peripheral neuropathy Iridoids Goshajinkigan 

Notes

Acknowledgement

This study was supported in part by a Grant-in-Aid for the Cooperative Research Project from Institute of Natural Medicine, University of Toyama in 2016 and 2017, JSPS KAKENHI Grant Number 15K07993 and 18K06728, Wakanyaku-Biotechnology Research Grant from Toyama prefecture, and JSPS Core-to-Core Program, Asia-Africa Science Platforms. The authors would like to thank Tsumura & Co. and Nippon funmatsu yakuhin Co., LTD, for providing the samples.

Compliance with ethical standards

Conflict of interest

The authors declare that they are no conflict of interest.

Supplementary material

11418_2019_1327_MOESM1_ESM.docx (146 kb)
Supplementary material 1 (DOCX 146 kb)

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Copyright information

© The Japanese Society of Pharmacognosy 2019

Authors and Affiliations

  1. 1.Division of Pharmacognosy, Institute of Natural MedicineUniversity of ToyamaToyamaJapan
  2. 2.Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan

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