Institute of Natural Medicine, University of Toyama, Sugitani, Toyama 930–0194, Japan.
Biol Pharm Bull. 2012;35(1):34-41. doi: 10.1248/bpb.35.34.
The protective effect of 7-O-galloyl-D-sedoheptulose (GS), isolated from Corni Fructus as an active component, against acute renal failure (ARF) induced by glycerol was investigated. The administration of GS led to a decline in the levels of blood urea nitrogen and creatinine; on the other hand, it did not have a significant effect on creatinine clearance. Furthermore, GS also significantly decreased the urine volume and fractional excretion of sodium, but it increased the urine osmolarity, suggesting the protective role of GS against renal dysfunction. Oxidative stress under ARF was attenuated by GS through the inhibition of lipid peroxidation, scavenging of reactive oxygen species (ROS), and elevation of the antioxidative status. Renal oxidative stress is related to the overproduction of ROS by nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase; therefore, in the present study, the protein expression of p22(phox) and NAD(P)H oxidase-4 (Nox-4) was investigated. GS down-regulated the protein expression of p22(phox); on the other hand, it did not significantly affect the expression of Nox-4. This indicates that GS inhibits the production of superoxide by regulating a component of NAD(P)H oxidase, p22(phox). Furthermore, GS down-regulated the expressions of nuclear factor-κB (NF-κΒ) and inducible nitric oxide (NO) synthase (iNOS), suggesting that GS protects against NO-induced inflammatory pathological conditions under ARF through the regulation of NF-κB and iNOS expressions. The present study indicates that GS exerts a protective effect against ARF through the recovery of renal dysfunction and attenuation of renal oxidative stress by regulating related protein expression.
从山茱萸中分离得到的 7-O-没食子酰基-D-熊果苷（GS）作为一种活性成分，其对甘油诱导的急性肾衰竭（ARF）的保护作用。GS 的给药导致血尿素氮和肌酐水平下降；另一方面，它对肌酐清除率没有显著影响。此外，GS 还显著降低了尿量和钠排泄分数，但增加了尿渗透压，表明 GS 对肾功能障碍具有保护作用。GS 通过抑制脂质过氧化、清除活性氧（ROS）和提高抗氧化状态来减轻 ARF 下的氧化应激。肾氧化应激与烟酰胺腺嘌呤二核苷酸磷酸（NAD（P）H）氧化酶产生的 ROS 过多有关；因此，在本研究中，研究了 p22（phox）和 NAD（P）H 氧化酶-4（Nox-4）的蛋白表达。GS 下调了 p22（phox）的蛋白表达；另一方面，它对 Nox-4 的表达没有显著影响。这表明 GS 通过调节 NAD（P）H 氧化酶的一个组成部分 p22（phox）来抑制超氧阴离子的产生。此外，GS 下调了核因子-κB（NF-κΒ）和诱导型一氧化氮合酶（iNOS）的表达，表明 GS 通过调节 NF-κB 和 iNOS 的表达来防止 ARF 下 NO 诱导的炎症病理状况。本研究表明，GS 通过调节相关蛋白表达恢复肾功能障碍和减轻肾氧化应激，发挥对 ARF 的保护作用。
