Protective effect of Liuwei Dihuang decoction on early diabetic nephropathy induced by streptozotocin via modulating ET-ROS axis and matrix metalloproteinase activity in rats RETRACTED ARTICLE

Abstract

We aimed to investigate the effects of Liuwei Dihuang decoction (LW) on the endothelin-1-reactive oxidative species (ET-ROS) system and matrix metalloproteinases (MMPs) in the early diabetic nephropathy induced by streptozotocin (STZ) in rats. Rats were divided into six groups as follows: the control group, the untreated model group, the treated groups with the LW (5, 10 and 15 g kg(-1), p.o.) and the aminoguanidine-treated group (100 mg kg(-1), orally). The treatment was performed for 4 weeks, beginning on the fifth week after one intraperitoneal injection of STZ (65 mg kg(-1)). In the untreated model group, increased blood glucose, decreased plasma insulin level and an impaired renal function were observed. There was an altered redox system shown by an increased malondialdehyde and decreased activity of glutathione peroxidase and superoxide dismutase in the renal cortex. An enhanced inducible nitric oxide synthetase, total nitric oxide synthase and constitutive nitric oxide synthase and a declined nitric oxide were found. An increased extracellular matrix was indicated by an abnormality of MMP-2 and MMP-9 activities and an increase in hydroxyproline. An up-regulated ET-1 level and increased mRNA expression of endothelin-converting enzyme, preproET-1 and ET( A) receptor were presented in the affected renal cortex, but no change in ET(B) receptor mRNA. The LW was most effective in reversing these changes in diabetic rats and was as effective as aminoguanidine. The benefits of the extracts in relieving the abnormalities in early diabetic nephropathy are likely to be mediated by suppression of the renal ET-ROS system and escalating the activity of MMPs.

Ethanol extracts of Rehmannia complex (Di Huang) containing no Corni fructus improve early diabetic nephropathy by combining suppression on the ET-ROS axis with modulate hypoglycemic effect in rats

“…), Corni fructus and Dioscorea opposite (Thunb.). This prescription is used and modified to contain more plant medicines in treating diabetes in China and Japan (Kitagawa et al, 1971;Kiho et al, 1992;Zhang et al, 1996;Yang et al, 2002;Yokozawa et al, 2004;He et al, 2007). Corni fructus is the most attractive and considered as effective fraction for isolating and testing its in relieving DN (Yamabe et al, 2007a(Yamabe et al, , 2007b.…”

Gifts from Chinese Medicine for diabetic nephropathy: Ancient formulas in modern times

“…However, only the effective mechanisms of Six-Ingredient Rehmannia Pill and Supplemented Kidney Qi Pill on diabetic nephropathy were explored in molecular biological level. Studies showed that both of the two formulas could reduce renal oxidative injury [9] and decrease expression of serum transforming growth factor~I(TGF-~I) [10], the mainly start factor of renal fibrosis.…”

Metabonomic analysis of the therapeutic effect of Zhibai Dihuang Pill in treatment of streptozotocin-induced diabetic nephropathy

“…Recently, animal experiments revealed its protective effect on renal injuries of diabetic nephropathy (DN) animal models (Yokozawa et al, 2004;Liu et al, 2008). Clinical studies also reported that ZDP exhibited potentials in the treatment of DN patients (Song et al, 2004;He et al, 2007). However, as TCM usually operates in vivo by multi-components, multiways and multi-targets (Xie et al, 2009), its molecular mechanism remains unclear.…”