Research Paper Volume 13, Issue 7 pp 10659—10671

Anti-inflammatory effect of resveratrol attenuates the severity of diabetic neuropathy by activating the Nrf2 pathway

Wanli Zhang2, *, , Huan Yu1, *, , Qingxia Lin3, *, , Xiaoqian Liu1, , Yifan Cheng2, , Binbin Deng2, ,

  • 1 Department of Pediatrics, Tianjin Children's Hospital, Beichen, Tianjin, P.R. China
  • 2 Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
  • 3 Department of Psychiatry, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, P.R. China
* Equal contribution

Received: June 24, 2020       Accepted: September 5, 2020       Published: March 26, 2021
How to Cite

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The mechanisms underlying the development of neuropathy associated with diabetes mellitus are not fully understood. Resveratrol, as a nonflavonoid polyphenol, plays a variety of beneficial roles in the treatment of chronic diseases such as Alzheimer's disease, coronary heart disease and obesity. In our study, the role of nuclear erythroid 2-related factor 2 (Nrf2) in resveratrol-mediated protection against streptozotocin-induced diabetic peripheral neuropathy (DPN) was investigated, and the antioxidant effect of resveratrol in diabetic peripheral nerves was studied. The STZ-treated model mice were divided into two groups. The resveratrol group was intragastrically administered 10 ml/kg 10% resveratrol once a day until the 12th week after STZ injection. The vehicle-treated mice were injected with the same volume of DMSO. Analysis of the effects of resveratrol in DPN revealed the following novel findings: (i) the pain and temperature sensitivities of diabetic mice were improved after treatment with resveratrol; (ii) Nrf2 expression was increased in the diabetic peripheral nerves of resveratrol-treated mice, and NF-KB pathway inhibition protected nerves upon resveratrol treatment in peripheral neuropathy; and (iii) resveratrol modulated the anti-inflammatory microenvironment of peripheral nerves by increasing Nrf2 activation and the expression of p-p65, and these changes may have been responsible for the neuroprotective effect of resveratrol in DPN, which was confirmed by Nrf2 knockout in diabetic mice. Overall, this study demonstrates that resveratrol may attenuate the severity of DPN by protecting peripheral nerves from apoptosis by inhibiting the NF-KB pathway and increasing Nrf2 expression.


DPN: Diabetic peripheral neuropathy; DM: Diabetes mellitus; Nrf2: nuclear factor 2 related factor 2; NF-KB: nuclear factor kappa-B; STZ: streptozotocin; TNF: tumor necrosis factor; keap1: kelch like; ECH: Associated Protein 1; HO-1: heme oxygenase (HO)-1; NQO1: quinone oxidoreductase 1; GCLC: glutamate-Cysteine Ligase Catalytic Subunit; MCP-1: monocyte Chemotactic Protein-1; TUNEL: terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling; IL-1: Interleukin-1.