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Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System

1
Faculdade de Farmácia, Universidade Federal da Bahia, CEP 40.170-115 Salvador, Brazil
2
Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, CEP 40.296-710 Salvador, Brazil
3
Universidade Federal do Recôncavo da Bahia, CEP 44.042-280 Feira de Santana, Brazil
4
Departamento de Ciências Exatas, Universidade Estadual de Feira de Santana, CEP 44.036-336 Feira de Santana, Brazil
5
Instituto de Química, Universidade Federal da Bahia, CEP 40.170-280 Salvador, Brazil
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(14), 4850; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144850
Received: 25 April 2020 / Revised: 3 May 2020 / Accepted: 6 May 2020 / Published: 9 July 2020
(This article belongs to the Section Bioactives and Nutraceuticals)
Diabetic neuropathy is a frequent complication of diabetes. Symptoms include neuropathic pain and sensory alterations—no effective treatments are currently available. This work characterized the therapeutic effect of bergenin in a mouse (C57/BL6) model of streptozotocin-induced painful diabetic neuropathy. Nociceptive thresholds were assessed by the von Frey test. Cytokines, antioxidant genes, and oxidative stress markers were measured in nervous tissues by ELISA, RT-qPCR, and biochemical analyses. Single (3.125–25 mg/kg) or multiple (25 mg/kg; twice a day for 14 days) treatments with bergenin reduced the behavioral signs of diabetic neuropathy in mice. Bergenin reduced both nitric oxide (NO) production in vitro and malondialdehyde (MDA)/nitrite amounts in vivo. These antioxidant properties can be attributed to the modulation of gene expression by the downregulation of inducible nitric oxide synthase (iNOS) and upregulation of glutathione peroxidase and Nrf2 in the nervous system. Bergenin also modulated the pro- and anti-inflammatory cytokines production in neuropathic mice. The long-lasting antinociceptive effect induced by bergenin in neuropathic mice, was associated with a shift of the cytokine balance toward anti-inflammatory predominance and upregulation of antioxidant pathways, favoring the reestablishment of redox and immune homeostasis in the nervous system. These results point to the therapeutic potential of bergenin in the treatment of painful diabetic neuropathy. View Full-Text
Keywords: neuropathic pain; diabetic neuropathy; natural product; analgesic; antioxidant; immunomodulation; cytokine; spinal cord; sciatic nerve neuropathic pain; diabetic neuropathy; natural product; analgesic; antioxidant; immunomodulation; cytokine; spinal cord; sciatic nerve
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MDPI and ACS Style

Villarreal, C.F.; Santos, D.S.; Lauria, P.S.S.; Gama, K.B.; Espírito-Santo, R.F.; Juiz, P.J.L.; Alves, C.Q.; David, J.M.; Soares, M.B.P. Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System. Int. J. Mol. Sci. 2020, 21, 4850. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144850

AMA Style

Villarreal CF, Santos DS, Lauria PSS, Gama KB, Espírito-Santo RF, Juiz PJL, Alves CQ, David JM, Soares MBP. Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System. International Journal of Molecular Sciences. 2020; 21(14):4850. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144850

Chicago/Turabian Style

Villarreal, Cristiane F., Dourivaldo S. Santos, Pedro S.S. Lauria, Kelly B. Gama, Renan F. Espírito-Santo, Paulo J.L. Juiz, Clayton Q. Alves, Jorge M. David, and Milena B.P. Soares 2020. "Bergenin Reduces Experimental Painful Diabetic Neuropathy by Restoring Redox and Immune Homeostasis in the Nervous System" International Journal of Molecular Sciences 21, no. 14: 4850. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144850

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