Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Eur J Pharmacol. 2010 Aug 25;640(1-3):233-42. doi: 10.1016/j.ejphar.2010.04.028. Epub 2010 May 3.
The aim of the present study was to evaluate the beneficial effects of 7-O-galloyl-D-sedoheptulose (GS), isolated from Corni Fructus, on hepatic and renal lipid metabolisms and advanced glycation endproduct formation followed by oxidative stress and inflammation using type 2 diabetic mice. GS was orally administered to db/db mice at doses of 20 and 100 mg/kg body weight per day for 8 weeks, and its effects were compared with those of the vehicle in db/db and m/m mice. The serum, hepatic, and renal biochemical factors, and protein expressions related to lipid metabolism, inflammation, advanced glycation endproducts, and their receptors, were measured. After 8 weeks of GS treatment, elevation of serum adiponectin as well as an improvement of hepatic and renal functional parameters was shown in db/db mice, and significant reductions of lipids in serum, liver, and kidney were observed according to the down-regulation of sterol regulatory element-binding protein-1. Moreover, GS inhibited oxidative stress and advanced glycation endproduct formation and their receptor expressions in the liver and kidney of db/db mice. These results suggest that GS could effectively inhibit advanced glycation endproduct formation caused by oxidative stress and/or dyslipidemia in the liver and kidney of db/db mice. Furthermore, the augmented expression of nuclear factor-kappa B p65 and its related inflammatory protein expressions were down-regulated in GS-treated groups. In conclusion, GS could have hepato- and reno-protective effects against abnormal lipid metabolism and the reactive oxygen species-related formation of advanced glycation endproducts with inflammation in type 2 diabetes.
本研究旨在评估从山茱萸中分离得到的 7-O-没食子酰基-D-景天庚酮糖(GS)对 2 型糖尿病小鼠肝肾功能、脂质代谢、晚期糖基化终产物形成以及氧化应激和炎症的有益作用。GS 以 20 和 100mg/kg 体重的剂量灌胃给药 8 周,观察其对 db/db 和 m/m 小鼠的作用,并与载体进行比较。检测血清、肝、肾生化因子及与脂质代谢、炎症、晚期糖基化终产物及其受体相关的蛋白表达。GS 治疗 8 周后,db/db 小鼠血清脂联素升高,肝肾功能参数改善,血清、肝脏和肾脏脂质水平降低,固醇调节元件结合蛋白-1 下调。此外,GS 抑制了 db/db 小鼠肝肾功能中氧化应激和晚期糖基化终产物的形成及其受体的表达。这些结果表明,GS 可有效抑制 db/db 小鼠肝肾功能中由氧化应激和/或血脂异常引起的晚期糖基化终产物的形成。此外,GS 处理组核因子-κB p65 及其相关炎症蛋白表达增加的情况得到下调。总之,GS 对 2 型糖尿病具有肝肾功能保护作用,可预防异常脂质代谢及与活性氧相关的晚期糖基化终产物的形成和炎症反应。