Therapeutic potential of Keishi-bukuryo-gan on diabetic nephropathy

Keishi-bukuryo-gan is a Chinese traditional medicine, which is used clinically as a vascular system disorder-eliminating drug. This review summarizes the effects of Keishi-bukuryo-gan on the occurrence and progression of diabetic nephropathy. To prove its usefulness, we employed two kinds of experimental model animals; diabetic nephropathy rats induced by subtotal nephrectomy plus streptozotocin injection and spontaneously diabetic WBN/Kob rats. In both animal models, Keishi-bukuryo-gan treatment suppressed increase of urinary protein excretion, which is a prognostically important clinical manifestation for renal functional deterioration in diabetic patients, and preserved renal morphological changes peculiar to diabetic glomerulosclerosis. On the other hand, disorders of the metabolic pathway mediated by persistent hyperglycemia (the glycation reaction, excessive polyol pathway and oxidative stress) were observed. However, oral administration of Keishi-bukuryo-gan normalized the accumulation of advanced glycation endproducts (AGEs), determined by measuring fluorescence, and lipid peroxidation levels in the kidney. Furthermore, by a comparison with aminoguanidine (an AGEs inhibitor), butylated hydroxytoluene (an antioxidant) and captopril (an angiotensin-converting enzyme inhibitor), we confirmed that Keishi-bukuryo-gan prevents diabetic kidney damage from developing and has inhibitory effects against AGEs accumulation and oxidative stress. From these results, we proposed the potential usefulness of Keishi-bukuryo-gan in the treatment of diabetic nephropathy.