Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Non-clinical safety assessment of Annona atemoya leaf extract: evaluation of genotoxicity

  • Eunjin Sohn (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • Bu‑Yeo Kim (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • Yu Jin Kim (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • Soo‑Jin Jeong (KM Convergence Research Division, Korea Institute of Oriental Medicine)
  • Received : 2023.09.20
  • Accepted : 2024.04.23
  • Published : 2024.07.15
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Abstract

The leaves, stems, and fruits of Annona atemoya (A. atemoya; AA), a fruit-bearing plant of the family Annonaceae, exhibit anti-angiogenic, anti-oxidative, anti-inflammatory, and neuroprotective activities. However, the safety of AA has not been comprehensively elucidated. In this study, we evaluated the potential genotoxicity of an AA leaf (AAL) ethanol extract using a standard three-test battery constituting in vitro mammalian chromosomal aberration, in vivo micronucleus, and bacterial reverse mutation (also known as the Ames test) tests, as recommended by the Ministry of Food and Drug Safety of Korea. In vitro chromosomal aberration assay revealed that AAL extract did not induce structural or numerical aberrations, with or without metabolic activation (S9). In vivo micronucleus assay revealed that the number of micronucleated polychromatic erythrocytes (PCEs) and the PCE/normochromatic erythrocyte ratio after AAL extract treatment were not substantially different from those in the negative control. Changes in body weight and mortality were not observed. However, AAL extract partially induced mutagenic activity in all three bacterial strains in the bacterial reverse mutation assay, indicating that it could potentially aid in determining the genotoxic safety of AAL. QuantSeq 3' mRNA sequencing analysis to elucidate the genotoxicity mechanisms of AAL extract using TK6 cells revealed that the genotoxic effects of AAL may be associated with cellular morphology-associated (cell development and keratinization), nucleotide metabolism, and electron transport chain functions.

Keywords

Acknowledgement

This study was supported by the Korea Institute of Oriental Medicine (KIOM, Grant No. KSN1515293), and the National Research Foundation of Korea (NRF) grant (NRF-2020R1A2C2012917), funded by the Ministry of Science and ICT (MSIT), Republic of Korea.

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