Biol. Pharm. Bull. 30(7) 1289—1296 (2007)

tions, such as atherosclerosis, cardiac dysfunction, retinopathy, neuropathy, and nephropathy. In longitudinal hyperglycemia, advanced glycation end-product (AGE) formation, resulting from the non-enzymatic reactions of carbohydrates and oxidized lipids with proteins, is increased and is also stimulated by oxidative stress which is closely linked with the pathogenesis of diabetic complications as well as the polyol pathway and protein kinase C pathway. Therefore, interference with AGE formation has the therapeutic potential to prevent the progression of diabetic complications. Traditional medicines are recently being focused on to treat diabetes and its complications because of their absence of toxicand/or side-effects. In our previous study, we reported that Hachimi-jio-gan ameliorated functional and structural features associated with experimental type 1 and 2 diabetic nephropathy rat models, and according to the three-dimensional HPLC profile of Hachimi-jio-gan, morroniside and loganin obtained from Corni Fructus (Cornus officinalis SIEB. et ZUCC.) are the major compounds. It was previously discovered that Corni Fructus could ameliorate glucose-associated metabolic disorders, and its mechanisms were intimately related to the formation of AGEs, as well as those of Hachimi-jio-gan. To add to these findings, we evaluated the major active components in Corni Fructus. As the first step, we prepared five fractions from Corni Fructus extract, that is, one sugar with organic acid fraction (S1D1), one iridoid glycoside fraction (S1D2), and three polyphenol fractions (from low to high molecular weights: S2, S3, and S4) as shown in Fig. 1A. Next, we examined the effect of Corni Fructus and its five fractions on hydroxyl radical scavenging activity associated with the glycation reaction, because this reaction is, in part, mediated by hydrogen peroxide and transition metal ions, called the Fenton reaction. As a result, only the fraction of S1D1 was weaker than Corni Fructus and S1D2 was similar to Corni Fructus; that is, the relation of these activities was as follows, “S1D1<Corni Fructus S1D2<S2<S3<S4.” In this study, we evaluated the active fractions of Corni Fructus, that is, one iridoid glycoside and three polyphenol fractions of S1D2, S2, S3, and S4, possessing greater activities compared with Corni Fructus, in streptozotocin (STZ)induced diabetic rats. This is the first report to clarify the active components not only in Corni Fructus but also in Hachimi-jio-gan against diabetes and associated renal damage.