Berberine ameliorates diabetic neuropathic pain in a rat model: involvement of oxidative stress, inflammation, and μ-opioid receptors

Naunyn Schmiedebergs Arch Pharmacol. 2019 Sep;392(9):1141-1149. doi: 10.1007/s00210-019-01659-6. Epub 2019 May 12.


Berberine, a chemical found in plants, is used as a supplement for diabetes. This study aimed to investigate the effects and the underlying molecular regulations of berberine in diabetic neuropathic pain in a rat model of diabetes. Rats were injected with streptozotocin (STZ) to induce diabetes and then were treated with berberine. Blood glucose levels and body weight were measured. Thermal and mechanical nociception were assessed by paw pressure test and hot tail immersion test. Oxidative stress was assessed by lipid peroxidation, production of reactive oxygen species (ROS) and catalase activity. Neuroinflammation was assessed by tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) protein levels. Finally, μ-opioid receptor (MOR) protein and mRNA levels were measured. We found that berberine treatment partially suppressed blood glucose levels and restored body weight in diabetic rats. Berberine also suppressed STZ-induced oversensitivity of mechanical and thermal nociception. Additionally, berberine partially suppressed oxidative stress and inflammation of diabetic rats. Finally, berberine significantly enhanced protein and mRNA expression levels of μ-opioid receptor (MOR). Our findings suggest that berberine is a potential therapeutic alleviating diabetes and diabetic neuropathic pain, probably through suppression of oxidative stress and neuroinflammation that may be mediated by MOR.

Keywords: Berberine; Diabetic neuropathic pain; Inflammation; Oxidative stress; μ-Opioid receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Berberine / pharmacology
  • Berberine / therapeutic use*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / metabolism
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Pain / drug therapy*
  • Pain / metabolism
  • Rats, Wistar
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Analgesics
  • Anti-Inflammatory Agents
  • Il6 protein, rat
  • Interleukin-6
  • Receptors, Opioid, mu
  • Tumor Necrosis Factor-alpha
  • Berberine