Standardized Aqueous Tribulus terristris (nerunjil) extract attenuates hyperalgesia in experimentally induced diabetic neuropathic pain model: role of oxidative stress and inflammatory mediators

Phytother Res. 2013 Nov;27(11):1646-57. doi: 10.1002/ptr.4915. Epub 2012 Dec 27.


The present study aimed to evaluate standardized aqueous Tribulus terristris (nerunjil) extract on the pain threshold response in streptozotocin (STZ)-induced diabetic neuropathic pain model in rats. After a single injection of STZ (40 mg/kg; i.p.), Wistar male rats were tested by the thermal and chemical-induced pain models. Diabetic rats exhibited significant hyperalgesia, and these rats were left untreated for the first four weeks. Thereafter, treatment was initiated and continued up to week-8. All the rats except the vehicle-treated group received insulin 5 IU/kg/day to maintain plasma glucose levels. Treatment with nerunjil (100 and 300 mg/kg; p.o.) for 4 weeks significantly attenuated the nociception in behavioural models. Nerunjil also inhibited the tumour necrosis factor-α and interleukin-1 beta levels. The effect of nerunjil (300 mg/kg) is comparable to the standard drug Pregabalin (100 mg/kg). Nerunjil increased the superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and decreased the lipid peroxide levels in dose-dependent manner. Insulin alone-treated rats failed to attenuate hyperalgesic response. In comparison to insulin alone-treated rats, nerunjil exhibited significant increase in the pain threshold response. It could be concluded that in controlled diabetic states, nerunjil attenuated the neuropathic pain through modulation of oxidative stress and inflammatory cytokine release.

Keywords: allodynia; cytokines; nerunjil; oxidative stress; streptozotocin; thermal analgesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalase / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Neuropathies / drug therapy*
  • Fruit / chemistry
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Hyperalgesia / drug therapy*
  • Inflammation / metabolism
  • Insulin / administration & dosage
  • Interleukin-1beta / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Medicine, Ayurvedic
  • Neuralgia / drug therapy
  • Oxidative Stress / drug effects*
  • Pain Threshold / drug effects
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Streptozocin
  • Superoxide Dismutase / metabolism
  • Tribulus / chemistry*
  • Tumor Necrosis Factor-alpha / metabolism


  • Insulin
  • Interleukin-1beta
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Streptozocin
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione