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

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Abstract

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.

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Acknowledgments

We are grateful to M. C. Santiago Xolalpa, IMSS herbarium, for authentication of plant material. We are grateful to the scholarship of IMSS Foundation A. C. given to Dr. Normand Garcia Hernandez. We would like to thank Editage (www.editage.com) for English language editing.

Funding

Contract/grant sponsor: Instituto Mexicano del Seguro Social (IMSS), number: FIS/IMSS/PROT/G18/1807.

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Contributions

NG and EP performed BSL tests and analysis of the data; RMaO and JRS performed the antilymphoma activity as well as analysis of the data; FC and MV performed the phytochemical fractionation of A. macroprophyllata. Also, FC conceived and supervised and wrote the original draft. All authors reviewed, commented, and approved the final manuscript.

Corresponding authors

Correspondence to Fernando Calzada or Rosa María Ordoñez-Razo.

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The authors declare that the procedures followed were in accordance with the regulations of the relevant clinical research ethics committee and with those of the Code of Ethics of the World Medical Association (Declaration of Helsinki).

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Calzada, F., Ramirez-Santos, J., Valdes, M. et al. Evaluation of Acute Oral Toxicity, Brine Shrimp Lethality, and Antilymphoma Activity of Geranylgeraniol and Annona macroprophyllata Leaf Extracts. Rev. Bras. Farmacogn. 30, 301–304 (2020). https://doi.org/10.1007/s43450-020-00014-8

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  • DOI: https://doi.org/10.1007/s43450-020-00014-8

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