Hesperidin improves motor disability in rat spinal cord injury through anti-inflammatory and antioxidant mechanism via Nrf-2/HO-1 pathway

Neurosci Lett. 2020 Jan 10:715:134619. doi: 10.1016/j.neulet.2019.134619. Epub 2019 Nov 9.

Abstract

Spinal cord injury (SCI) is associated with inflammation with concurrent oxidative stress and glial activation. The aim of this study was to evaluate whether hesperidin, a representative flavonoid in citrus fruits, ameliorates SCI-induced motor dysfunction and neuro-pathologic degeneration in rat model. Rats received hesperidin (100 mg/kg body weight/daily, oral administration) from 7 days prior to SCI to 7 days post SCI. Behavioral test was done on rats with SCI until 6 weeks. For the study of inflammatory molecules in SCI rats with hesperidin treatment, rats were sacrificed at day 4 post SCI, and spinal cords were collected and studied histopathologically. Behavioral tests on hind-limbs of rats with SCI revealed that treatment of hesperidin in rats with SCI significantly ameliorate the hind-limb paralysis beginning at day 21 post SCI. Hesperidin treatment in rats with SCI reduced the neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) and pro-inflammatory cytokines including tumor necrotic factor-α and interleukin-1β. In addition, oxidative stress related molecules including superoxide dismutase, catalase, nuclear factor erythroid 2-related factor-2 and heme oxygenase-1 were also increased by hesperidin treatment. Furthermore, Fe2+, bilirubin and p38 mitogen activated protein kinase, these by-product of heme catabolism in serum and spinal cord of rats with hesperidin-treatment groups were significantly increased compared with those of vehicle-treatment group. Collectively, this study implies that hesperidin accelerates recovery of locomotor function and tissue repair of damaged spinal cord, with concurrent upregulation of heme oxygenase-1 as far as rat SCI model is concerned.

Keywords: Heme oxygenase-1; Hesperidin; Motor disability; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Bilirubin / blood
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Hesperidin / pharmacology*
  • Hindlimb / drug effects
  • Iron / blood
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • Paralysis / prevention & control*
  • Rats
  • Signal Transduction / drug effects*
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / complications
  • Spinal Cord Injuries / prevention & control*
  • p38 Mitogen-Activated Protein Kinases / blood

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Iron
  • Hesperidin
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • p38 Mitogen-Activated Protein Kinases
  • Bilirubin