Naringenin downregulates inflammation-mediated nitric oxide overproduction and potentiates endogenous antioxidant status during hyperglycemia

Abstract

Nitric oxide (NO) is a key regulating factor for physiological functions, when elevated during inflammatory conditions can lower endogenous antioxidant levels. Increased NO interacts with oxygen or other ROS to generate peroxynitrite, a potent oxidant which induces oxidative stress. Analgesic effects of naringenin (NRN), a flavanone has been demonstrated by inducing anti-inflammatory effects in O2-*-mediated inflammation. NRN stimulates antioxidant enzymes and also improves glucose uptake. Hence this study was designed to look for therapeutic effects of NRN and in comparison, to metformin (MET) on inflammation-mediated increased NO and decreased antioxidant superoxide dismutase (SOD) in diabetic rat model with compromised glycemic and lipid profile. After single intraperitoneal injection of alloxan (120 mg/kg), the rats were equally divided as Group 1 and 2 which received normal saline and no-treatment respectively while group 3 and 4 received MET 50 mg/kg/day and NRN 50 mg/kg/day respectively. Blood samples were collected at 0, 15th and 30th day of treatment period. Results showed that alloxan significantly increased serum level of glucose (P<0.001), NO (P<0.001) and inflammatory biomarkers (TNF-, IL-6), however, it expressively decreased serum SOD and insulin level. While, NRN significantly downregulated glucose (P<0.05), lipid profile, TNF-, IL-6 and normalized level of NO (P<0.01). It also improved SOD level as compared to that of MET-treatment. Histopathology of pancreas also showed significant improvement in morphology after NRN treatment. This work delivers that NRN exerts anti-oxidant effect in part by downregulating the inflammation-mediated NO overproduction and improving level of SOD resulting in potentiation of endogenous antioxidant defense.