Cytotoxicity, Phagocytic Activity, and Leishmanicidal Potential of Extract Standardized in Geranylgeraniol Obtained from the Fruit 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 IC50 for 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.