Rokumi-jio-gan-containing prescriptions regulate oxidative stress through improving dyslipidemia in a subtotal nephrectomized rat model.

Abstract: Ethnopharmacological relevance: Rokumi-jio-gan-containing prescriptions, traditional medicine, are widely used to treat renal dysfunction in Japan. Aim of the study: The present study was conducted to examine whether two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) have an ameliorative effect on dyslipidemia in nephrectomized rats. Materials and methods: Each prescription was orally administered to nephrectomized rats at 150mg/kg body weight per day for 10 weeks, and its effect was compared with vehicle-treated nephrectomized rats. Results: Rats given Hachimi-jio-gan and Bakumi-jio-gan showed an improvement of renal functional parameters such as serum urea nitrogen, creatinine, creatinine clearance, and urinary protein. The increased triglyceride, total cholesterol, non-esterified fatty acid, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol/low-density lipoprotein cholesterol levels in serum, and triglyceride and total cholesterol contents in the kidney of nephrectomized rats were significantly decreased by Hachimi-jio-gan and Bakumi-jio-gan administration. Furthermore, Hachimi-jio-gan acts as a regulator of peroxisome proliferator-activated receptor α, sterol regulatory element binding protein (SREBP)-1, and SREBP-2. On the contrary, the increased reactive oxygen species and thiobarbituric acid-reactive substance were decreased, while superoxide dismutase and the reduced glutathione/oxidized glutathione ratio were augmented by Hachimi-jio-gan rather than Bakumi-jio-gan. The improvement of nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, NF-E2-related factor 2, and heme oxygenase-1 was marked in the group administered Bakumi-jio-gan. However, oil red O staining showed that the increased lipid deposition in the kidney of nephrectomized rats improved on Hachimi-jio-gan and Bakumi-jio-gan administration. Conclusion: This study provides scientific evidence that two Rokumi-jio-gan-containing prescriptions (Hachimi-jio-gan and Bakumi-jio-gan) improve oxidative stress via dyslipidemia in the remnant kidney of nephrectomized rats. [Copyright &y& Elsevier]