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
{"title":"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。","authors":"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","doi":"10.1002/jat.4684","DOIUrl":null,"url":null,"abstract":"<p><i>Rubus imperialis</i> (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 <i>Rubus</i> 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 <i>CYP3A4</i> (metabolism), <i>M-TOR</i> (cell death), and <i>CDKN1A</i> (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.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"44 12","pages":"1886-1896"},"PeriodicalIF":2.7000,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth\",\"authors\":\"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\",\"doi\":\"10.1002/jat.4684\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><i>Rubus imperialis</i> (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 <i>Rubus</i> 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 <i>CYP3A4</i> (metabolism), <i>M-TOR</i> (cell death), and <i>CDKN1A</i> (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.</p>\",\"PeriodicalId\":15242,\"journal\":{\"name\":\"Journal of Applied Toxicology\",\"volume\":\"44 12\",\"pages\":\"1886-1896\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Applied Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jat.4684\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jat.4684","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Risk assessment of 2β,3β-19α-trihydroxyursolic acid from Rubus imperialis (Rosaceae) in HepG2/C3A cells via genotoxicity, metabolism, and cell growth
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.
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.
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