Effects of two formulations for overcoming oketsu on vascular function and expression patterns of plasma proteins in spontaneously diabetic rats

We investigated the effects of keishibukuryogan and tokishakuyakusan, which are representative formulations for overcoming oketsu, on vascular function and expression patterns of plasma proteins in spontaneously diabetic rats. Twenty-one- to 24-week-old male WBN/Kob rats were maintained for 18 weeks on a diabetes-accelerated feed, and received standard (diabetes-accelerating) chow containing 3% (wt/wt) keishibukuryogan or tokishakuyakusan for 25 weeks. There was no significant change in body weight or blood glucose among the groups. Acetylcholine-induced endothelium-dependent relaxation of the keishibukuryogan group significantly increased compared to that of controls. Xanthine/xanthine oxidase-induced contraction of the tokishakuyakusan group and phospholipase A₂-induced contraction of the keishibukuryogan and tokishakuyakusan groups significantly decreased compared to the controls. Transit time of whole blood tended to decrease in the tokishakuyakusan group compared to controls. NO₂^-/NO₃^- in the keishibukuryogan and tokishakuyakusan groups significantly decreased compared to controls. A study using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) demonstrated that five and eight peaks had significantly changed peak intensities in plasma of rats treated with keishibukuryogan and tokishakuyakusan, respectively, as compared to the controls. Thus, two representative formulations for overcoming oketsu with different mechanisms of action had favorable effects against vascular dysfunction. Altered plasma protein levels were commonly observed in the rats administered these two formulations. Our study using ProteinChip technology may be useful for the evaluation of the relationship between the efficacy and the profiling of plasma protein expression after administration Kampo medicines, thus leading to the understanding of “Sho” in Kampo medicine.