Toxicological Studies on Biological Effects of the Herbal Drug Extracts in Rats and Mice : Peony Root, Peach Kernel, Japanese Angelica Root and Cnidium Rhizome

For the investigation of biological adverse effects of herbal drugs, toxicological studies were performed on the methanolic extracts from Peony root (syakuyaku), Peach kernel (toonin), Japanese angelica root (tooki) and Cnidium rhizome (senkyuu) in rats and mice. In the single administration study, these extracts were administered orally or intraperitoneally to male Wistar rats and ddY mice at a dose of 6g/kg (peach kernel, 4g/kg), and acute toxic effects of the extracts were investigated. In the repeated administration study, these extracts were orally administered by intubation to male Wistar rats once a day for 21 d at daily doses of 1.5 and 3g/kg (peach kernel, 0.25 and 0.5g/kg). General appearance and body weight of rats were checked daily, and behavioral, hematological, biochemical and pathological examinations were performed. The results obtained are given as follows. 1) Single administration study. Peony root, Japanese angelica and Cnidium rhizome did not show any sign of toxicity in rats and mice by oral administration, whereas these herbal drugs showed some toxic signs and/or lethal effect by intraperitoneal administration. No species difference in the toxic signs was found between rats and mice. Peach kernel showed a marked lethal effect in both of the animal species by oral administration, but not by intraperitoneal administration. The lethal effect is considered to be due to the toxic action of the cyanide produced from amygdalin in the digestive tract of the animals. Peach kernel also induced rearing and fighting behaviors in rats, but not in mice, by intraperitoneal administration. 2) Repeated administration study. Peony root : Body weight gain was suppressed. Macrocytic anemia was observed in hematological examination. The osmotic resistance of the erythrocytes slightly increased. Spleen weight increased, and a dilatation and congestion in the sinusoid of the spleen were evidenced by pathological observation. However, no evidence of hemolytic anemia was obtained in pathological and biochemical examinations in which no abnormal sign of hemosiderin deposition in the liver and the spleen and no increase in total bilirubin level in the serum were found. The activity of glycylprolyl-dipeptidyl aminopeptidase in both of the serum and the liver and the content of cyt. P-450 in the kidney also increased. Peach kernel and Japanese angelica root : The increases in the serum free cholesterol level and the kidney cyt. P-450 content were observed. Cnidi