Ferulsinaic acid attenuation of diabetic nephropathy

Different factors are involved in the development of diabetic nephropathy (DN). Oxidative stress and inflammation play an important role in the pathogenesis of DN. Ferulsinaic Acid (FA) was isolated in 2007. In 2011, we found that FA prolonged the lifespan of C. elegans due to its antioxidative effect, and we hypothesized that FA restores the kidney function of diabetic rats via its antioxidant activity.

Male Wistar rats were injected with STZ and divided into 5 groups of 10 each: control, diabetic untreated, diabetic treated with 500, 750 and 1000 ng/kg FA. FA treatment was continued for 21 weeks after induction of diabetes.

In the diabetic rats treated with FA, fasting blood sugar, HbA1C kidney/body weight ratio, creatinine, BUN, sodium and albuminurea were significantly decreased compared with untreated diabetic rats. Diabetic rats showed decreased activities of superoxide dismutase, glutathione peroxidase and catalase, increased concentrations of malondialdehyde and IL-6 in the kidney homogenate. In addition levels of 8-hydroxy-2'-deoxyguanosine in the urine and in the renal cortex DNA were increased. Moreover, severe destruction in glomerular and tubulointerstitial lesions such as glomerular sclerosis, atrophy, interstitial expansion and interstitial cellular infiltration was seen in the kidney of the diabetic untreated rats. Furthermore, the diabetic kidney was found to be positive for NF-κB p65 antigen in the immunohistochemistry examinations. Treatment with FA restored all the altered parameters in a dose-dependent manner. Furthermore, all the ultra-morphologic abnormalities and NF-κB activation in the kidney of diabetic rats were markedly ameliorated by FA treatment.

FA confers a considerable protection against kidney injuries of the diabetic rats by increasing activities of antioxidant enzymes, attenuating the formation of AGEs, attenuating the NF-κB activation, ameliorating the inflammatory markers and inhibiting the accumulation of oxidized DNA in the kidney, suggesting a potential drug for the prevention and therapy of DN.