Umbelliprenin relieves paclitaxel-induced neuropathy

Author:

Shahraki Jafar1,Rezaee Ramin23,Mohammadzehi Kenar Sabereh1,Setoodeh Nezhad Samaneh1,Bagheri Gholamreza4,Jahantigh Hosseinali5,Tsarouhas Konstantinos6,Hashemzaei Mahmoud1ORCID

Affiliation:

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

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.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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