The Antioxidative Effects of Astragalus Saponin I Protect Against Development of Early Diabetic Nephropathy

Abstract

Abstract. It has been known that oxidative stress plays an important role in the development of diabetic nephropathy (DN). The antioxidative effects of Astragalus saponin I (AS I) were studied in vitro and in vivo. In the presence of high glucose and H 2 O 2 , the total antioxidative capability, catalase, reduced glutathione, and superoxide dismutase level of rat mesangial cells were significantly decreased, and transforming growth factor β1 (TGF-β1) mRNA level, collagen IV, and laminin level were significantly increased. When compared with those in the high glucose group, these 4 indexes of cells incubated in 2.0 and / or 20 µmol / L of AS I were significantly enhanced, and levels of TGF-β1 mRNA, collagen IV and laminin were statistically decreased. By flowcytomery, percentages of S phase of cells incubated in high glucose and H 2 O 2 were lowered, while those in AS I were increased. Furthermore, the physical behaviors of rats treated with 12 mg / kg of AS I restored with vigor and weight gaining, while the level of HbAlC was significantly reduced. Thus, AS I has antioxidative effects and is a potential compound worth further study because it may prevent the development of DN.

Over-production of nitric oxide by oxidative stress-induced activation of the TGF-β1/PI3K/Akt pathway in mesangial cells cultured in high glucose

“…In the present study, both high glucose and H 2 O 2 led to npg increased TGF-β1 protein and mRNA expression in rat MCs, and these were then reduced by treatment with DPI, suggesting that ROS mediated high glucose-induced TGF-β1 production. Our previous reports have demonstrated that TGF-β1 protein and mRNA expression were increased in the renal cortices of diabetic rats [6][7][8] . These findings indicate that TGF-β1 plays an important role during hyperglycemia.…”

“…TGF-β1, a very important growth factor in DN pathogenesis, has been reported to be up-regulated in the kidney under diabetic conditions using in vitro [20][21][22][23]25] and in vivo [6][7][8]24] studies. In the present study, both high glucose and H 2 O 2 led to npg increased TGF-β1 protein and mRNA expression in rat MCs, and these were then reduced by treatment with DPI, suggesting that ROS mediated high glucose-induced TGF-β1 production.…”

“…Over-production of reactive oxygen species (ROS) and oxidative stress are the direct consequences of hyperglycemia [3,4] , and excessive mitochondrial ROS serve as a common upstream mediator of diabetic complications [5] . Our previous research demonstrated that extracts from herbal medicines could prevent DN progression by scavenging ROS [6][7][8] .…”

“…Data from other laboratories [20][21][22] and our team [6][7][8][23][24][25] have demonstrated www.nature.com/aps Zhai YP et al Acta Pharmacologica Sinica npg that transforming growth factor β1 (TGF-β1) is the core factor that contributes to DN pathogenesis. Most of the studies on the pathologic effects of TGF-β1 on DN simply focus on its profibrotic effect, while other potential mechanisms remain unclear.…”

Renoprotective Effect of Total Glucosides of Paeony (TGP) and Its Mechanism in Experimental Diabetes

“…More important, several investigations in the setting of experimental diabetic nephropathy using different drugs, such as mycophenolate mofetil, methotrexate, and erythromycin, have shown that prevention of the development or amelioration of renal injury in diabetes is associated with ant-inflammatory actions (3 -6). More recently, much attention has also been focused on the role of oxidative stress, and it has been suggested that oxidative stress might constitute the key and common events in the pathogenesis of diabetic nephropathy (7,8). Therefore, amelioration of diabetic oxidative stress may prevent or attenuate renal abnormalities associated with diabetes.…”