Biol. Pharm. Bull. 30(3) 520—526 (2007)

chronic hyperglycemia, and glucose participates in diabetic complications such as atherosclerosis, cardiac dysfunction, and nephropathy. Chronic hyperglycemia accelerates activation of the formation of advanced glycation end-products (AGEs), oxidative stress, the polyol pathway, and protein kinase C pathway. These metabolic factors are synergistically correlated with one another; therefore, an effective treatment with wide-spread effects continues to be required. Up to now, there have been many experiments focusing on the treatment of diabetes and its complications with traditional medicines including Chinese prescriptions because of their absence of toxic and/or side-effects. In our previous study, we reported that the Chinese prescriptions Hachimijio-gan and Keishi-bukuryo-gan had potential therapeutic effects against diabetic nephropathy, and had different functions in terms of their effects on metabolic disorders, especially on AGE formation in Hachimi-jio-gan and oxidative stress in Keishi-bukuryo-gan. In addition, we also clarified that administration of dried Rehmanniae Radix (Rehmannia glutinosa LIBOSCH. var. purpurea MAKINO) extract, which is the main constituent of Hachimi-jio-gan, attenuates renal dysfunction in diabetic nephropathy mainly due to its suppression of oxidative stress; however, for the analysis of this prescription, further characterization of the other constituents is needed. According to the three-dimensional HPLC profile, as previously shown, morroniside, loganin, and paeoniflorin were detected as the major compounds in Hachimi-jio-gan. Morroniside and loganin are the components of Corni Fructus (Cornus officinalis SIEB. et ZUCC.) and paeoniflorin is the component of Moutan Cortex (Paeonia suffruticosa ANDREWS) common in Keishi-bukuryogan. Therefore, in order to clarify the source of a particular action of Hachimi-jio-gan, we chose to evaluate the usefulness of one of the crude drugs, Corni Fructus. Corni Fructus has been used as a traditional medicine in Japan and China, and the components of this plant are iridoid total glycoside such as morroniside and loganin and also a few polyphenols such as cornusiin A, B, and C, monomeric and trimeric hydrolysable tannins, and so on. Recently, it has been reported that Corni Fructus has a plasma glucoselowering action in normal rats, along with anti-neoplastic and anti-microbial effects. Moreover, Vareed et al. also reported that Corni Fructus has been used for improving liver and kidney functions, and iridoid total glycoside has the effect of preventing the overexpression of transforming growth factor (TGF)-b1 and matrixes in glomeruli with a diabetic model. However, the mechanisms of Corni Fructus against glucose-associated metabolic disorders in diabetes have yet to be explored. To determine whether Corni Fructus possesses the principal role in Hachimi-jio-gan, which has a strong effect on AGE formation in diabetes and/or diabetic nephropathy, we examined the effect of Corni Fructus in streptozotocin (STZ)-induced diabetic rats, comparing it with the inhibitor of AGE formation, aminoguanidine.