THE TOXIC PRINCIPLE OF TSANG-ER-TZU(THE SEED OF XANTHIUM STRUMARIUM L.)AND ITS PHARMACOLOGICAL ACTIONS

Tsang-Er-Tzu, one of the vegetable drugs commonly used in Chinese medicine, is the seed of Xanthium strumarium L. of the family of Compositae. Occasional poisonings and deaths have occurred among children and domestic animals after ingesting the drug. The oil of Tsang-Er-Tzu was found to be nontoxic to rats and mice, whereas the aqueous extract produced toxic effects such as sluggishness, lowering of body temperature, dyspnea, polyuria, convulsions and death. From the aqueous extract two ingredients were isolated, of which the protein was shown to be nontoxic, whereas the glycosidal substance (AA₂) showed toxic actions similar to the aqueous extract. The LD₅₀ of AA₂ after intraperitoneal injection was found to be 10 mg/kg for mice and 4.6 mg/kg for rats. Rats given AA2 (1.25—5.0 mg/kg) intraperitoneally showed a fall of blood sugar. Two to four hours following a large dose (10mg/kg) of AA₂ the blood sugar of the animals dropped to convulsion levels which inevitably resulted in death. However, if 5 ml a 20% glucose solution was administered prior to convulsion, the survival time of the animals was prolonged for about 4 hours. When rats were made hyperglycemic by alloxanization, AA₂ was unable to lower the blood sugar. On the other hand, AA2 could affect the hyperglycemia induced by adrenaline injection. A single dose (0.6 mg/kg i.m.) of adrenaline produced hyperglycemia lasting for about 2 hours. When adrenaline and AA2 were injected simultaneously, the hyperglycemia waned more rapidly. If AA2 was injected prior to adrenaline, however, no or only mild increase of blood sugar was observed. Moreover, AA₂ injection significantly lowered the liver glycogen both in rats and in mice. It appears, therefore, that the mechanism of AA₂ in lowering the blood sugar was not due to increased deposition of glycogen in the liver. When anaesthetized and unanacsthetized rats were injected with AA₂ at a dose of 5 mg/kg intraperitoneally, a significant drop of blood pressure was observed. In addition, administration of AA₂ 4.0 mg/kg to rats produced a precipitous fall of total leucocyte counts. However, if the animals survived, the leucocyte counts were restored to normal levels. No significant alteration of vascular permeability of the rats was observed by injections of small doses of AA2. When the symptoms of poisoning were obvious, the vascular permeability of the liver and the spleen in rats seemed to be increased.