Berberine Ameliorates Diabetic Neuropathy: TRPV1 Modulation by PKC Pathway

Am J Chin Med. 2017;45(8):1709-1723. doi: 10.1142/S0192415X17500926. Epub 2017 Nov 9.


In recent years, berberine has increasingly become a topic of research as a treatment for diabetes due to its repair function, which recovers damaged pancreatic β cells. However, it is the complications of diabetes that seriously affect patients' life quality and longevity, among which diabetic neuropathy and the consequent acute pain are the most common. In this study, we established STZ-induced diabetic models to observe whether berberine, a main constitute of Coptis chinensis Franch which has shown good hypoglycemic effects, could relieve diabetes-induced pain and explored its possible mechanism in rats and mice. Behavior assays showed increasing mechanical allodynia and thermal hyperalgesia thresholds by the Von Frey test and tail flick test during the treatment of berberine. It was found that the administration of berberine (20, 60 mg/kg; 30, 90 mg/kg) suppressed the expression of PKCε and TRPV1 which could be activated by hyperglycemia-induced inflammatory reaction. Our results also presented its capability to reduce the over expression of TNF-[Formula: see text] in diabetic rats and mice. TNF-[Formula: see text] is an inflammatory cytokine, which is closely related to diabetic peripheral neuropathy (DPN). Consequently, we supposed that berberine exerts its therapeutic effects in part by suppressing the inflammatory process and blocking the PKC pathway to inhibit TRPV1 activation, which damages neurons and causes diabetic pain.

Keywords: Berberine; Diabetic Peripheral Neuropathy; Inflammation; PKCε; STZ; TNF-; TRPV1.

MeSH terms

  • Animals
  • Berberine / administration & dosage*
  • Berberine / pharmacology*
  • Diabetes Mellitus, Experimental
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Disease Models, Animal
  • Mice
  • Phytotherapy*
  • Protein Kinase C / metabolism*
  • Protein Kinase C / physiology
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Streptozocin
  • TRPV Cation Channels / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism


  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Tumor Necrosis Factor-alpha
  • Berberine
  • Streptozocin
  • Protein Kinase C