NF-kappaB inhibitory action of resveratrol: a probable mechanism of neuroprotection in experimental diabetic neuropathy.
Resveratrol has shown array of biological actions, and is under clinical development for various disease conditions. The etiology of diabetic neuropathy revolves around oxidative stress, AGE formation, lipid peroxidation etc. All these stimulate inflammatory processes and NF-kappaB cascade is considered as one of the major players of inflammatory response. Activation of NF-kappaB results in elevated levels of inflammatory mediators. COX-2 and TNF-alpha activity have also been correlated with inflammatory damage in the pathophysiology of diabetic neuropathy (DN). Therefore we investigated the effect of resveratrol on NF-kappaB inflammatory cascade, COX-2, TNF-alpha and IL-6 levels in experimental DN. We found that resveratrol protected against various functional and behavioral deficits in diabetic neuropathy in line with our earlier published reports. In this study we found that the resveratrol treatment decreased the expression of p65 and IkappaB-alpha in treated rats. Treatment also ameliorated the elevated levels of TNF-alpha, IL-6 and COX-2. Resveratrol treatment produced significant decrease in nerve MDA levels in treated animals which may also be contributing to reduction in neuro-inflammation. This study confirms the NF-kappaB inhibitory activity and anti-inflammatory activity of resveratrol which may contribute to neuroprotection in diabetic neuropathy apart from its antioxidant effect.
Kumar
Ashutosh
A
Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062, India.
Sharma
Shyam S
SS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000517:prevention & control*; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D018696:Neuroprotective Agents; C000606206:Nfkbia protein, rat; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; D000077185:Resveratrol