Resveratrol alleviates nuclear factor-κB-mediated neuroinflammation in vasculitic peripheral neuropathy induced by ischaemia–reperfusion via suppressing endoplasmic reticulum stress

Po Ting Pan, Han Yu Lin, Ching Wei Chuang, Po‑Kai Wang, Hung Chieh Wan, Ming Cheng Lee, Ming Chang Kao

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Vasculitic peripheral neuropathy (VPN) arises from an inflammatory obstruction in the blood vessels supplying peripheral nerves and subsequent ischaemic insults, which exhibits the clinical features of neuropathic pain and impaired peripheral nerve function. VPN induced by ischaemia–reperfusion (IR) has been reported to involve nuclear factor-κB (NF-κB)-mediated neuroinflammation. Recent studies have suggested that endoplasmic reticulum (ER) stress has been implicated in the development of peripheral neuropathies. Resveratrol possesses a potent anti-inflammatory capacity. We hypothesized that resveratrol may exert a protective effect against VPN through modulating the interrelated ER stress and NF-κB pathways. Male Sprague-Dawley rats were allocated into five groups: sham, sham + resveratrol 40 mg/kg (R40), IR, IR + R20 and IR + R40. VPN was induced by occluding the right femoral artery for 4 hours followed by reperfusion. Our data have shown that VPN induced by IR led to hind paw mechanical allodynia, heat hyperalgaesia, and impaired motor nerve conduction velocity (MNCV). With resveratrol intervention, the behavioural parameters were improved in a dose-dependent manner and the MNCV levels were increased as well. The molecular data revealed that VPN induced by IR significantly increased the expression of NF-κB as well as the ER stress sensor proteins, protein kinase RNA-like endoplasmic reticulum kinase, inositol-requiring enzyme 1 and activating transcription factor 6 in the sciatic nerves. More importantly, resveratrol significantly attenuated the expression of NF-κB and the ER stress sensor proteins after IR. In conclusion, resveratrol alleviates VPN induced by IR. The mechanisms may involve modulating NF-κB-mediated neuroinflammation via suppressing ER stress.

Original languageEnglish
Pages (from-to)770-779
Number of pages10
JournalClinical and Experimental Pharmacology and Physiology
Volume46
Issue number8
DOIs
Publication statusPublished - Aug 2019
Externally publishedYes

Keywords

  • endoplasmic reticulum stress
  • neuroinflammation
  • neuropathic pain
  • polyphenol
  • resveratrol

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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