Evaluation of Acute Oral Toxicity, Brine Shrimp Lethality, and Antilymphoma Activity of Geranylgeraniol and Annona macroprophyllata Leaf Extracts

In this study, we investigated the acute oral toxicity, brine shrimp lethality, and the antilymphoma activity of geranylgeraniol and the ethanolic and petroleum ether extracts of Annona macroprophyllata Donn. Sm., Annonaceae, leaves. Leaves were extracted by maceration with ethanol or petroleum ether. In acute oral toxicity analysis, the ethanolic extract had a LD50 of 1587 mg/kg, while the petroleum ether extract had an LD50 of > 3000 mg/kg. This indicated that the petroleum ether extract may be less harmful than the ethanolic extract. Furthermore, the petroleum ether extract showed low acute toxicity (category 5), significant brine shrimp lethality, and a high antilymphoma activity. Therefore, petroleum ether extract was purified by preparative thin layer chromatography to yield geranylgeraniol. The results showed that geranylgeraniol (LC50 = 1.00 μg/ml) was more potent than methotrexate (LC50 24.66 μg/ml), a known chemotherapy drug. Additionally, geranylgeraniol showed high antilymphoma activity in Balb/c mice injected intraperitoneally with 1 × 106 U-937 of human leukemic monocyte lymphoma cells, resulting in 50% effective inhibitory concentration (EC50) values of 4.38 mg/kg and 3.66 mg/kg for male and female mice, respectively. The antilymphoma activity of geranylgeraniol was similar to that of methotrexate (EC50 = 1.07 mg/kg and 1.33 mg/kg, respectively). These findings suggest that geranylgeraniol may serve as a potential natural compound for the treatment of lymphoma.