Umbelliprenin relieves paclitaxel-induced neuropathy

  • J Pharm Pharmacol. 2020 Dec;72(12):1822-1829. doi: 10.1111/jphp.13365.
Jafar Shahraki  1 Ramin Rezaee  2  3 Sabereh Mohammadzehi Kenar  1 Samaneh Setoodeh Nezhad  1 Gholamreza Bagheri  4 Hosseinali Jahantigh  5 Konstantinos Tsarouhas  6 Mahmoud Hashemzaei  1
Affiliations
  • 1. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran.
  • 2. Clinical Research Unit, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 3. Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 4. Faculty of Health, Zabol University of Medical Sciences, Zabol, Iran.
  • 5. Department of Pathology, Zabol University of Medical Sciences, Zabol, Iran.
  • 6. Department of Cardiology, University Hospital of Larissa, Larissa, Greece.
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.
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