Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

Molecules. 2015 Aug 14;20(8):14959-69. doi: 10.3390/molecules200814959.

Abstract

Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in "itch-scratch" animal models is under investigation.

Keywords: atopic dermatitis; dorsal root ganglion neurons; nerve growth factor; yokukansankachimpihange.

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Animals
  • Bupleurum
  • Cell Death / drug effects
  • Cells, Cultured
  • Drugs, Chinese Herbal / pharmacology*
  • Ganglia, Spinal / growth & development*
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / pharmacology
  • Male
  • Nerve Growth Factor / pharmacology*
  • Neurites / drug effects
  • Neurites / metabolism*
  • Oleanolic Acid / analogs & derivatives
  • Oleanolic Acid / chemistry
  • Oleanolic Acid / pharmacology
  • Oxindoles
  • Plant Extracts / pharmacology
  • Rats, Sprague-Dawley
  • Saponins / chemistry
  • Saponins / pharmacology
  • Uncaria / chemistry

Substances

  • Alkaloids
  • Bupleurum root extract
  • Drugs, Chinese Herbal
  • Indole Alkaloids
  • Oxindoles
  • Plant Extracts
  • Saponins
  • yokukansankachimpihange
  • rhyncophylline
  • Oleanolic Acid
  • Nerve Growth Factor
  • saikosaponin D
  • hirsutine