Bergapten Ameliorates Vincristine-Induced Peripheral Neuropathy by Inhibition of Inflammatory Cytokines and NFκB Signaling

ACS Chem Neurosci. 2019 Jun 19;10(6):3008-3017. doi: 10.1021/acschemneuro.9b00206. Epub 2019 May 23.

Abstract

Bergapten, a furanocoumarin derivative found in a variety of medicinal plants, is documented to possess anti-inflammatory activity. However, whether bergapten is useful in alleviating the symptoms as well as the progress of peripheral neuropathy is not yet studied. The current investigation has been designed to explore the effect of bergapten on vincristine-induced neuropathic pain. Rats were grouped as normal, neuropathic control (vincristine), gabapentin, and bergapten treated groups with five animals in each group. Vincristine (100 μg/kg, i.p.) was administered for 10 days with 2 days break. Gabapentin (60 mg/kg, i.p.) and bergapten (10 mg/kg i.p.) treatments were given once daily for 14 days. The animals were assessed for hyperalgesia and allodynia. After 14 days, animals were sacrificed to detect plasma pro-inflammatory cytokines (TNF α, IL-1β), spinal cord, and sciatic nerve oxidative stress and expression of iNOS, COX-2, and NFkB in the spinal cord. There was a marked reduction in pain behaviors in the bergapten group as compared to the vincristine group. Bergapten also attenuated pro-inflammatory cytokines (TNFα and IL-1β), oxidative stress, and expression of NFkB, COX-2, and iNOS. Overall the current study concludes that bergapten could serve as a potential lead to drug development for the treatment of neuropathic pain.

Keywords: Bergapten; NFκB; allodynia; hyperalgesia; neuropathic pain; pro-inflammatory cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methoxypsoralen / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / toxicity*
  • Cytokines / drug effects
  • Inflammation / metabolism
  • Male
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neuralgia / chemically induced*
  • Neuralgia / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Vincristine / toxicity*

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents, Phytogenic
  • Cytokines
  • NF-kappa B
  • 5-Methoxypsoralen
  • Vincristine