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Wen-Pi-Tang, an Oriental medical prescription composed of Rhei Rhizoma, Ginseng Radix, Aconiti Tuber, Zingiberis Rhizoma and Glycyrrhizae Radix, is used clinically as a medicine to treat renal failure. This study was conducted to examine the inhibitory activity of the five crude drug components of Wen-Pi-Tang and several pure compounds isolated from Rhei Rhizoma and Glycyrrhizae Radix against the protein glycation reaction. Rhei Rhizoma exerted the most potent activity, Zingiberis Rhizoma and Glycyrrhizae Radix showed relatively moderate activity, whereas Aconiti Tuber and Ginseng Radix showed weak activity. On the other hand, of 20 compounds obtained from Rhei Rhizoma and Glycyrrhizae Radix, tannins, especially rhatannin, RG-tannin and procyanidin B-2 3,3′-di-O-gallate, showed significantly strong activities that were more effective than the positive control, aminoguanidine. Some flavones such as licochalcone A and licochalcone B, and anthraquinones such as emodin and aloe-emodin, also showed inhibitory activity. These findings may help to explain, at least in part, certain pharmacological activities of Wen-Pi-Tang, whose clinical efficacy against renal failure is already recognized.

Wen-Pi-Tang is a Chinese prescription used traditionally as a medicine to treat moderate renal failure. In this study, we used rats subjected to subtotal nephrectomy and streptozotocin injection to examine the effects of Wen-Pi-Tang on diabetic nephropathy. Wen-Pi-Tang was administered at a dose of 50, 100 or 200 mg/kg body weight/day for 15 weeks. Diabetic nephropathy is one of the most serious chronic complications of diabetes mellitus, and renal dysfunction is reflected by proteinuria, decreased creatinine clearance (Ccr) and increased serum urea nitrogen and creatinine (Cr) levels. Wen-Pi-Tang treatment for 15 weeks resulted in significant reductions of blood glucose and serum urea nitrogen levels, while proteinuria, Ccr and serum Cr levels did not change significantly. Wen-Pi-Tang also lowered serum triglyceride and thiobarbituric acid-reactive substance levels in a dose-dependent manner. Furthermore, the disorders of the glucose-dependent metabolic pathway due to this pathological condition were normalized by the administration of Wen-Pi-Tang through decreased formation of advanced glycation end-products in the kidney. Wen-Pi-Tang protected against the development of renal lesions, glomerular sclerosis and mesangial matrix expansion, assessed by histopathological evaluation and scoring. This study suggests that Wen-Pi-Tang treatment could be beneficial in reducing the risk of developing diabetic nephropathy.

Oxidative stress plays a key role in the pathophysiologic process of acute and chronic renal diseases. Intracellular component such as lipids, proteins and nucleic acids are easily and rapidly oxidized by excessive reactive oxygen species (ROS), and such reactions lead to increased levels of lipid peroxide. The present study examined the antioxidant effects of Wen-Pi-Tang and its component crude drugs on 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)- or 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN)-induced ROS generation and lipid peroxidation of linoleic acid. As a result, Wen-Pi-Tang significantly decreased AAPH or AMVN-induced ROS in renal mitochondrial particles. For the components in Wen-Pi-Tang's prescription, Rhei Rhizoma and Glycyrrhizae Radix extracts strongly inhibited peroxide levels, but Ginseng Radix, Aconiti Tuber and Zingiberis Rhizoma extracts were comparably low. Rhei Rhizoma extract showed the strongest inhibitory activity on oxidative injury, and two of its tannin compounds, (-)-epicatechin 3-O-gallate and procyanidin B-2 3,3′-di-O-gallate, inhibited AAPH or AMVN-induced ROS significantly. Thus, the present data suggest that Wen-Pi-Tang and its component crude drugs effectively prevent biological toxicity on oxidative stress through potent antioxidant and anti-lipid peroxidation activities.

Wen-Pi-Tang, a traditional Chinese prescription, has been widely used for the treatment of patients with moderate chronic renal failure in China. Although the protective effect of Wen-Pi-Tang on peroxynitrite (ONOO^-)-induced renal tubular epithelial LLC-PK₁ cell damage was elucidated in our previous research, the active components of Wen-Pi-Tang have not yet been fully clarified. Therefore in the present study, we investigated the active components by using a cellular ONOO^-generation system. As a result, p-coumaric acid, 4-(4'-hydroxylphenyl)-2-butanone 4'-O-glucopyranoside, gallic acid 3-O-(6'-O-galloyl)-β-d-glucopyranoside, procyanidin B-1, procyanidin B-3, and (+)-catechin were isolated as active compounds inhibiting cellular ONOO^- formation and cytotoxicity. In particular, the content of (+)-catechin was significantly higher than those of the other compounds, and the (+)-catechin structure was located in procyanidins B-1 and B-3. Therefore, the major bioactivity of Wen-Pi-Tang against ONOO^--induced cytotoxicity in LLC-PK₁ cells was thought to be mediated by (+)-catechin. Although we cannot disregard the synergetic effect of various components in Wen-Pi-Tang, (+)-catechin is a major active compound protecting against ONOO^--induced LLC-PK₁ cell damage and may be used as an index to qualify the ONOO^--inhibitory activity of Wen-Pi-Tang extract.