Analyzing the role of cannabinoids as modulators of Wnt/β-catenin signaling pathway for their use in the management of neuropathic pain

Bioorg Med Chem Lett. 2019 May 1;29(9):1043-1046. doi: 10.1016/j.bmcl.2019.03.013. Epub 2019 Mar 11.

Abstract

Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/β-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (1-6) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/β-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/β-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt/β-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.

Keywords: Anti-proliferative activity; Cannabinoids; Cannabis sativa; Neuropathic pain; Wnt/β-catenin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cannabinoids / chemistry*
  • Cannabinoids / pharmacology
  • Cannabinoids / therapeutic use
  • Cannabis / chemistry
  • Cannabis / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Neuralgia / drug therapy
  • Neuralgia / pathology
  • Plant Leaves / chemistry
  • Plant Leaves / metabolism
  • Wnt Signaling Pathway / drug effects*

Substances

  • Cannabinoids