Umbelliprenin relieves paclitaxel-induced neuropathy

J Pharm Pharmacol. 2020 Dec;72(12):1822-1829. doi: 10.1111/jphp.13365. Epub 2020 Sep 15.

Abstract

Objectives: Umbelliprenin (UMB) is a prenylated coumarin that acts as an in vitro antioxidant and inhibits lipoxygenase managing the inflammation pathways, while in vivo it exerts anti-inflammatory activities.

Methods: In this study, neuropathic pain was induced by four intraperitoneal doses of 2 mg/kg per day of paclitaxel (PTX) on days 1, 3, 5 and 7. Here, 49 male mice were randomly divided in the following groups: sham (not treated animals), negative control (PTX-treated receiving normal saline), single-dose UMB 6.25, 12.5 and 25 mg/kg groups (PTX-treated receiving UMB 6.25, 12.5 and 25 mg/kg, respectively), prevention (PTX-treated receiving PTX along with UMB 12.5 mg/kg on days 1, 3, 5 and 7) and positive control group (PTX-treated receiving imipramine 10 mg/kg as acute treatment). Hot-plate test was done to assess response to heat. Finally, interleukin (IL)-6 levels in the sciatic nerve and lipid peroxidation in sera were assessed.

Key findings: Umbelliprenin was found equally effective for acute treatment with imipramine, when comparing the prevention group and the positive control group. Single, 25 mg/kg UMB effectively attenuated hyperalgesia, lipid peroxidation and IL-6 levels.

Conclusions: Umbelliprenin alleviated neuropathic pain, and decreased serum IL-6 levels and oxidative stress. UMB deserves further investigations, especially in clinical settings.

Keywords: Ferula; coumarins; neuropathic pain; oxidative stress; sesquiterpene; taxane.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Disease Models, Animal
  • Interleukin-6 / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Paclitaxel
  • Pain Threshold / drug effects
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / physiopathology
  • Sciatic Neuropathy / chemically induced
  • Sciatic Neuropathy / metabolism
  • Sciatic Neuropathy / physiopathology
  • Sciatic Neuropathy / prevention & control*
  • Umbelliferones / pharmacology*

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Antioxidants
  • Il6 protein, rat
  • Interleukin-6
  • Umbelliferones
  • umbelliprenin
  • Paclitaxel