Harpagophytum procumbens Extract Ameliorates Allodynia and Modulates Oxidative and Antioxidant Stress Pathways in a Rat Model of Spinal Cord Injury

Neuromolecular Med. 2020 Jun;22(2):278-292. doi: 10.1007/s12017-019-08585-z. Epub 2020 Jan 3.


Spinal cord injury (SCI) is a deliberating disorder with impairments in locomotor deficits and incapacitating sensory abnormalities. Harpagophytum procumbens (Hp) is a botanical widely used for treating inflammation and pain related to various inflammatory and musculoskeletal conditions. Using a modified rodent contusion model of SCI, we explored the effects of this botanical on locomotor function and responses to mechanical stimuli, and examined possible neurochemical changes associated with SCI-induced allodynia. Following spinal cord contusion at T10 level, Hp (300 mg/kg, p.o.) or vehicle (water) was administered daily starting 24 h post-surgery, and behavioral measurements made every-other day until sacrifice (Day 21). Hp treatment markedly ameliorated the contusion-induced decrease in locomotor function and increased sensitivity to mechanical stimuli. Determination of Iba1 expression in spinal cord tissues indicated microglial infiltration starting 3 days post-injury. SCI results in increased levels of 4-hydroxynonenal, an oxidative stress product and proalgesic, which was diminished at 7 days by treatment with Hp. SCI also enhanced antioxidant heme oxygenase-1 (HO-1) expression. Concurrent studies of cultured murine BV-2 microglial cells revealed that Hp suppressed oxidative/nitrosative stress and inflammatory responses, including production of nitric oxide and reactive oxygen species, phosphorylation of cytosolic phospholipases A2, and upregulation of the antioxidative stress pathway involving the nuclear factor erythroid 2-related factor 2 and HO-1. These results support the use of Hp for management of allodynia by providing resilience against the neuroinflammation and pain associated with SCI and other neuropathological conditions.

Keywords: Allodynia; Harpagophytum procumbens; Inflammation; Microglia; Oxidative stress; Spinal cord injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / metabolism
  • Animals
  • Drug Evaluation, Preclinical
  • Gene Expression Regulation / drug effects
  • Harpagophytum / chemistry*
  • Heme Oxygenase (Decyclizing) / biosynthesis
  • Heme Oxygenase (Decyclizing) / genetics
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / etiology
  • Inflammation
  • Male
  • Mice
  • Motor Activity / drug effects
  • NF-E2-Related Factor 2 / biosynthesis
  • NF-E2-Related Factor 2 / genetics
  • Nitric Acid / metabolism
  • Oxidative Stress / drug effects*
  • Phytotherapy*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Single-Blind Method
  • Spinal Cord Injuries / complications*
  • Touch


  • Aldehydes
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Plant Extracts
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • 4-hydroxyhexenal
  • Nitric Acid
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • 4-hydroxy-2-nonenal