Cytotoxicity, phagocytic activity, and leishmanicidal potential of extract standardized in geranylgeraniol obtained from the fruit of Pterodon emarginatus vogel

Suzana Ferreira Alves; Clayson Moura Gomes; Matheus Gabriel de Oliveira; Wanessa Machado de Andrade; Larissa Cleres Moreira; Leonardo Luiz Borges; Cláudio Carlos da Silva; Graciella Ottoni de Souza; Vinicius Barreto da Silva; Marize Campos Valadares; Maria Teresa Freitas Bara

Articles

Abstract

Pharmacognosy Magazine,2020,16,67,140-147.

DOI:10.4103/pm.pm_231_19

Published:February 2020

Type:Original Article

Authors:

Author(s) affiliations:

Suzana Ferreira Alves¹, Clayson Moura Gomes², Matheus Gabriel de Oliveira³, Wanessa Machado de Andrade⁴, Larissa Cleres Moreira⁵, Leonardo Luiz Borges⁶, Cláudio Carlos da Silva⁷, Graciella Ottoni de Souza⁷, Vinicius Barreto da Silva⁸, Marize Campos Valadares⁵, Maria Teresa Freitas Bara³
¹ Faculty of Pharmacy, Natural Products Research Laboratory, Federal University of Goiás; Pharmacy Course, School of Medical Sciences, Pharmaceuticals and Biomedical Sciences, Pontifical Catholic University of Goiás, Anápolis, Go, Brazil
² Pharmacy Course, School of Medical Sciences, Pharmaceuticals and Biomedical Sciences, Pontifical Catholic University of Goiás; Institute of Tropical Pathology and Public Health, Anápolis, Go, Brazil
³ Faculty of Pharmacy, Natural Products Research Laboratory, Federal University of Goiás, Anápolis, Go, Brazil
⁴ Pharmacy Course, School of Medical Sciences, Pharmaceuticals and Biomedical Sciences, Pontifical Catholic University of Goiás; Faculty of Pharmacy Laboratory of Pharmacology and Cell Toxicology – Farmatec, Federal University of Goiás, Anápolis, Go, Brazil
⁵ Faculty of Pharmacy Laboratory of Pharmacology and Cell Toxicology – Farmatec, Federal University of Goiás, Anápolis, Go, Brazil
⁶ Pharmacy Course, School of Medical Sciences, Pharmaceuticals and Biomedical Sciences, Pontifical Catholic University of Goiás; Pharmacy Course, University Unit of Exact and Technological Sciences, State University of Goiás, Anápolis, Go, Brazil
⁷ Replicon Research Center, Department of Biology, Pontifical Catholic University of Goiás, Goiânia, Brazil
⁸ Pharmacy Course, School of Medical Sciences, Pharmaceuticals and Biomedical Sciences, Pontifical Catholic University of Goiás, Anápolis, Go, Brazil

Abstract:

Aim: The propouse of this study was to available the cytotoxicity, phagocytic activity, and leishmanicidal potential of extract standardized from the fruits of Pterodon emarginatus Vogel. Background: P. emarginatus is a Brazilian medicinal plant with several constituents shown to have anti-inflammatory, antinociceptive, antimicrobial, and antiproliferative activities. Materials and Methods: The standardized extract in geranylgeraniol obtained from the fruit of P. emarginatus was investigated for clastogenic and cytotoxic effects, as well as phagocytic activity against Leishmania guyanensis. Results: A 24-h exposure of Allium cepa roots to standardized geranylgeraniol extract (9.77 mg/mL) promoted clastogenic effects, with a mitotic index (MI) of 10.33 ± 0.61. Extending the exposure time to 48 or 72 h significantly reduced the MI (P < 0.05). The IC50for geranylgeraniol in 3T3 and RAW 264.7 cells was found to be 15.5 mg/mL and 12.2 mg/mL, respectively. The standardized extract in geranylgeraniol exhibited high phagocytic and microbicidal activities in Leishmania, promoting a >60% increase in macrophage infection, with greater internalization and destruction of the parasite. In silico study results suggest that geranylgeraniol acts in Leishmania by interfering with the biosynthesis of sterols through steric hindrance of the active site of the enzyme CYP51. Conclusion: The standardized extract in geranylgeraniol may be useful as an antiproliferative agent, macrophage immunomodulator, and as a cytotoxic treatment against infectious agents.