Bitter Principles of Cucurbitaceæ

Sm,-Through the courtesy of Dr. D. A. Sutton of the National Chemical Research Laboratory, Pretoria, we have had an opportunity of examining several pure crystalline compounds recently isolated from species of Cucumis by Dr. Enslinl of that laboratory. To assist others who may be interested in this field we desire to report on the toxicities and certain pharmacological properties of the substances examined. Cucurbitacin A, derived from Cucumis myriocarpus and C. leptodermis, was administered intraperitoneally to groups of five male albino mice at three dose levels (0.62, 1.25 and 2.5 mg./kg.), and groups of two female albino rats at three dose levels (1.0, 2.0 and 4.0 mg./kg.). The estimates of the LD50 according to Karber’s formula2, were found to be 1.2 mg. /kg. and 2 mg. ,’kg. for mice and rats respectively. Respiratory distress was observed at lethal or near lethal doses and at autopsy some rats showed evidence of acute pulmonary edema. This phenomenon was also observed in a rabbit anzesthetised with 1.8 g. /kg. of urethane intravenously. A total of 6 mg. /kg. given intravenously in divided doses over a three-hour period caused respiratory distress followed by death. Approximately 5 ml. of blood stained fluid was drained post-mortem from the bronchial tree. In a cat anssthetised with chloralose, 60 mg. /kg. intravenously, the compound had no appreciable immediate effects on the blood pressure and respiration, when given intravenously in amounts which varied from 0.04 to 0.32 mg. /kg. This cat was also given Cucurbitacin B which also had no apparent immediate effect. The animal, however, died with acute pulmonary edema after a total of 0.7 mg. /kg. of Cucurbitacin A and 0.3 mg. /kg. of Cucurbitacin B. A quantity of about 10 ml. of fluid was collected from the bronchial tree after death by postural drainage and compression of the chest wall. Macroscopically, the lungs were congested and a cut section exuded a pinkish fluid on pressure ; the lungs did not sink in water. Histological examination revealed engorgement of the blood vessels. Cucurbitacin B, obtained chiefly from Cucumis africanus and Lagenria leucantha was administered intraperitoneally to groups of five male albino mice at three dose levels (0.62, 1.25 and 2.5 mg./kg.). Lethal doses again caused pulmonary edema and the LD50 according to Karber’s formula2 was 1 mg. /kg. Cucurbitacin C , obtained from Cucumis sativus had an intraperitoneal LD50, according to Karber’s formula2, of 0.8 mg. /kg. in male albino mice. Five animals were used at each dose of 0.62, 1.25 and 2.5 mg. /kg. Respiratory distress was again observed with lethal and near lethal doses. Groups of two female albino rats received amounts up to 4 mg. /kg. without causing death but at this dose respiratory distress was present. The dihydro derivative of Cucurbitacin A was also examined and found to be considerably less toxic. Amounts up to 80 mg. /kg. intraperitoneally had no apparent effect in male albino mice. Intravenous administration of doses up to 5 mg. /kg. in a rabbit, anzesthetised with urethane, 1.5 g. /kg. intravenously, did not apparently increase the respiratory tract secretion. A total of approximately 12 mg. /kg. was given over a four and a half hour period. Due to the small quantities of the materials available and to their low solubilities, the investigations were necessarily limited. The results, however, indicate quite clearly that Cucurbitacin A, B and C are comparatively toxic compounds, lethal amounts causing acute pulmonary edema. The dihydro