Effects of traditional Japanese (Kampo) medicines (orengedokuto, goreisan and shichimotsukokato) on the onset of stroke and expression patterns of plasma proteins in spontaneously hypertensive stroke-prone rats

We investigated the effects of three traditional Japanese medicines (TJMs), orengedokuto, goreisan and shichimotsukokato on the onset of stroke and survival ratio in stroke-prone spontaneously hypertensive rats (SHRSP), and examined the expression patterns of plasma proteins before and after the onset of stroke. Thirty-two 7-week-old male SHRSP were randomly assigned to four groups. The control group received distilled water. Rats in the orengedokuto, goreisan and shichimotsukokato groups received distilled water containing 0.3% (wt/wt) orengedokuto, goreisan and shichimotsukokato extracts, respectively, from 9 to 20 weeks old. Blood pressure was measured at 12 and at 14 weeks old. Body weight was measured and blood samples were obtained weekly. Plasma samples were analyzed by Protein Chip technology. As for body weight loss after stroke onset, mean body weight in the control group decreased after 14 weeks old, but those in the orengedokuto, goreisan and shichimotsukokato groups showed no decrease at 20 weeks old. Systolic blood pressure showed no significant differences among the four groups at 14 weeks old. The survival ratios of the orengedokuto, goreisan and shichimotsukokato groups were significantly enhanced compared to the control group. Analysis of plasma proteins showed changes in 15 peaks between before and after the onset of stroke in the 3,000-30,000 Da mass ranges in the control group. Especially the peaks at m/z 9,330, 9,480 and 9,700 remarkably decreased after the onset of stroke in the control group. These peaks were identified by western blot analysis as haptoglobin. Interestingly, the decrease was partially prevented by the administration of three TJMs. These results suggest that orengedokuto, goreisan and shichimotsukokato suppress the onset of stroke in SHRSP independently from the mechanism of an anti-hypertensive effect. At the same time, TJMs affect the expression of proteins associated with the onset of stroke in SHRSP.