Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth

IF 2.7 4区医学 Q3 TOXICOLOGY

Journal of Applied Toxicology Pub Date : 2024-08-11 DOI:10.1002/jat.4684

Bruna Oshiiwa, Aline Pereira da Silva, Greice Rafaele Alves, Valdir Cechinel Filho, Rivaldo Niero, Isabel O'Neill de Mascarenhas Gaivão, Liana Martins de Oliveira, Luan Vitor Alves de Lima, Mário Sérgio Mantovani, Edson Luis Maistro

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引用次数: 0

Abstract

Rubus imperialis (Rosaceae) is a Brazilian medicinal plant that already exhibited therapeutical perspectives. However, previous studies revealed cellular and/or genetic toxicity of extracts from aerial parts of this plant, as well as other species of the Rubus genus. Being 2β,3β-19α-trihydroxyursolic acid (2B) one of the major compounds of this plant, with proven pharmacological effect, it is important to investigate the biosafety of this isolated compound. Therefore, in the present study, (2B) was tested by several cytogenotoxic endpoints up to 20 μg/ml in human hepatoma HepG2/C3A cells. The test compound did not produce any decreased cell viability, DNA damage, chromosomal mutations, cell cycle changes, or apoptotic effects in the tested cells. Additionally, RT-qPCR analysis revealed the downregulation of CYP3A4 (metabolism), M-TOR (cell death), and CDKN1A (cell cycle) genes. Under the experimental conditions used, the 2B compound did not show cytogenotoxic activity after a single exposure to HepG2/C3A human cells.

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通过遗传毒性、新陈代谢和细胞生长，评估帝王蔷薇（蔷薇科）中的 2β,3β-19α-三羟基熊果酸在 HepG2/C3A 细胞中的风险。

茜草（蔷薇科）是巴西的一种药用植物，已经显示出治疗前景。然而，以前的研究表明，从这种植物的气生部分以及茜草属的其他物种中提取的提取物具有细胞和/或遗传毒性。2β,3β-19α-三羟基熊果酸（2B）是这种植物的主要化合物之一，具有公认的药理作用，因此研究这种分离化合物的生物安全性非常重要。因此，本研究在人肝癌 HepG2/C3A 细胞中对 (2B) 进行了几项细胞毒性终点测试，最高浓度为 20 μg/ml。受试化合物未在受试细胞中产生任何细胞活力下降、DNA 损伤、染色体突变、细胞周期变化或细胞凋亡效应。此外，RT-qPCR 分析显示 CYP3A4（代谢）、M-TOR（细胞死亡）和 CDKN1A（细胞周期）基因下调。在所使用的实验条件下，2B 化合物在单次接触 HepG2/C3A 人体细胞后未显示出细胞毒性活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Applied Toxicology 医学-毒理学

CiteScore

7.00

自引率

6.10%

发文量

145

审稿时长

1 months

期刊介绍： Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.