Effects of the Japanese Kampo herbal medicines, Oren-Gedoku-To and Toki-Shakuyaku-San, on ischemic changes in the rat brain induced by permanent occlusion of the bilateral common carotid arteries

The effects of Oren-Gedoku-To (TJ-15) and Toki-Shakuyaku-San (TJ-23) on cerebral ischemic changes were analyzed in Wistarrats. TJ-15 (group A), TJ-23 (group B) or distilled water (group C) was given through a catheter inserted into the stomach every day for 14 days. Under general anesthesia, the common carotid arteries were tied and cut bilaterally. Drug or distilled water was given every day until 30 days after the surgery. Overall, 6/13, 5/12, and 5/12 rats in groups A, B, and C, respectivery, died. In group A, 3/6 died within 2 days after the surgery (early phase) and the other 3 animals died within 11-14 days after the surgery (late phase). In groups B and C, each of the 5 animals died within a few days. The death rate at the early phase in groups A, B and C was 23, 42, and 42%, respectively, and the rate was significantly low in group A. In surviving animals, infarction was seen in the cortices and/or hippocampus. The rates of appearance of infarction were 0/7 (0%), 1/7 (14%), and 5/7 (71%) in groups A, B, and C, and the rates in groups A and B were significantly low compared to group C. VEGF positive cells were apparent in the surrounding area of infarction, but there were no significant differences in their rate of appearance or distribution in the animals with infarction in the three groups. bFGF positive cells were also significantly increased in the surrounding area of infarction and no significant differences were noted among the animals with infarction in the three groups. Both ER (estrogen receptor) positive cells and PgR (progesterone receptor) positive cells were observed in the hypothalamus of all animals. There were no changes in numbers of ER and PgR positive cells in the three groups. The concentrations of estrogen (estrone, estriol and estradiol) in the blood showed no differences in the three groups. Based on our results, it is suggested that TJ-15 exerted, a protective effect against ischemic changes in the acute and chronic phases, while TJ-23 exerted a protective effect against ischemic changes in the chronic phase.