Analgesic effect of coumarins from Radix angelicae pubescentis is mediated by inflammatory factors and TRPV1 in a spared nerve injury model of neuropathic pain

J Ethnopharmacol. 2017 Jan 4:195:81-88. doi: 10.1016/j.jep.2016.11.046. Epub 2016 Nov 30.

Abstract

Ethnopharmacological relevance: Coumarins from Radix angelicae pubescentis (CRAP) are a major active component that are isolated from dried roots of Angelica biserrata Yuan et Shan, which has been used clinically to cure headaches for a long period of time, and it is an effective treatment for pain. The aim of the present study was to investigate the analgesic effect of CRAP on a spared nerve injury (SNI) model of neuropathy.

Materials and methods: Antinociceptive effects of CRAP were assessed in Sprague-Dawley male rats using a spared nerve injury model of neuropathic pain. Inflammatory factors were determined by Enzyme-linked immunosorbent assay (ELISA). Transient receptor potential cation channel 1 (TRPV1) and Phosphorylated extracellular regulated protein kinases (pERK) were detected by Immunofluorescence and Western blotting, respectively.

Results: The high performance liquid chromatography (HPLC) analysis showed the presence of osthole and columbianadin in Radix angelicae pubescentis. CRAP induced the dose-dependent effect of on attenuating the development of mechanical hypersensitivity. Molecular profiling revealed that CRAP reduced the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) and significantly attenuated the expression of TRPV1 and pERK in damaged DRG neurons.

Conclusion: This results demonstrate that CRAP possess remarkable antinociceptive activities which may be due to osthole and columbianadin at least in part, supporting the folkloric usage of the plant to treat various pain diseases.

Keywords: Coumarin; Neuropathic pain; Radix angelicae pubescentis; TRPV1; pERK.

MeSH terms

  • Analgesics / isolation & purification
  • Analgesics / pharmacology*
  • Angelica / chemistry*
  • Animals
  • Chromatography, High Pressure Liquid
  • Coumarins / isolation & purification
  • Coumarins / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / physiopathology
  • Inflammation Mediators / metabolism*
  • Male
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Neuralgia / physiopathology
  • Pain Threshold / drug effects
  • Phosphorylation
  • Phytotherapy
  • Plant Roots / chemistry
  • Plants, Medicinal
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • TRPV Cation Channels / drug effects*
  • TRPV Cation Channels / metabolism
  • Time Factors

Substances

  • Analgesics
  • Coumarins
  • Inflammation Mediators
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • columbianadin
  • Extracellular Signal-Regulated MAP Kinases
  • osthol