Sohn Eunjin, Kim Bu-Yeo, Kim Yu Jin, Jeong Soo-Jin
KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054 Republic of Korea.
Toxicol Res. 2024 May 16;40(3):473-485. doi: 10.1007/s43188-024-00241-4. eCollection 2024 Jul.
The leaves, stems, and fruits of (; 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.
The online version contains supplementary material available at 10.1007/s43188-024-00241-4.
番荔枝科的一种结果植物（；AA）的叶、茎和果实具有抗血管生成、抗氧化、抗炎和神经保护活性。然而，AA的安全性尚未得到全面阐明。在本研究中，我们按照韩国食品药品安全部的建议，使用包括体外哺乳动物染色体畸变、体内微核和细菌回复突变（也称为艾姆斯试验）试验的标准三项试验组合，评估了AA叶（AAL）乙醇提取物的潜在遗传毒性。体外染色体畸变试验表明，AAL提取物在有或无代谢活化（S9）的情况下均未诱导结构或数量畸变。体内微核试验表明，AAL提取物处理后多染性红细胞（PCE）的微核数量和PCE/正常染色红细胞比率与阴性对照相比无显著差异。未观察到体重和死亡率的变化。然而，AAL提取物在细菌回复突变试验中对所有三种细菌菌株均部分诱导了诱变活性，表明它可能有助于确定AAL的遗传毒性安全性。使用TK6细胞进行的QuantSeq 3' mRNA测序分析以阐明AAL提取物的遗传毒性机制，结果显示AAL的遗传毒性作用可能与细胞形态相关（细胞发育和角质化）、核苷酸代谢以及电子传递链功能有关。
在线版本包含可在10.1007/s43188-024-00241-4获取的补充材料。
