一个新兴的植物风险评估工具箱

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters Pub Date : 2025-09-01 DOI:10.1016/j.toxlet.2025.07.050

C. Mahony

{"title":"一个新兴的植物风险评估工具箱","authors":"C. Mahony","doi":"10.1016/j.toxlet.2025.07.050","DOIUrl":null,"url":null,"abstract":"<div><div>The HESI Developmental and Reproductive Toxicology (DART) Working Group of the Botanical Safety Consortium is dedicated to developing reliable screening strategies to identify botanicals with potential developmental or reproductive toxicity. Our mission encompasses the selection of <em>in silico</em> and <em>in vitro</em> tools capable of accommodating the complex mixtures inherent in botanicals, as well as the evaluation of candidate botanicals based on suspected DART endpoints. We have established a series of botanical case studies to assess the efficacy of a NAM toolbox based on functional as well mechanistic assays.</div><div>In our recent evaluations, we identified several botanicals that have been studied for DART effects. Blue cohosh (Caulophyllum thalictroides), traditionally used to induce labour, was associated with fetal bovine cardiac defects. Usnea Lichen affected estrous cycling in a 90-day rodent study, and usnic acid demonstrated teratogenic effects in rats and zebrafish. Conversely, ashwagandha, Asian ginseng, and milk thistle are not expected to cause DART effects.</div><div>Selected assays, such as Devtox Quick Predict and transcriptional profiling with Connectivity Mapping, were employed to explore their utility in identifying DART-relevant botanicals. Notably, the Devtox assay revealed significant changes in cystine and ornithine metabolism for blue cohosh and usnea lichen, indicating a high potential for developmental toxicity. Ginseng showed changes in cystine metabolism alone, and no response was detected with ashwagandha. Although milk thistle exhibited changes in both metabolites, these occurred at concentrations affecting cell viability. Connectivity Mapping (CMap) analysis linked blue cohosh to compounds like GABA receptor antagonists, acetylcholinesterase inhibitors, and mycophenolic acid, all of which are associated with adverse reproductive outcomes. Ginseng connections included ginsenosides and various agents with potential stimulating and hormonal effects.</div><div>The data generated from this research will be made publicly available via the NIEHS database. As we continue, we aim to refine our data analysis and expand our assays and botanical repertoire to enhance safety decision-making processes in botanical evaluation.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S16"},"PeriodicalIF":2.9000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"S03-01 An emerging toolbox for Botanical risk assessment\",\"authors\":\"C. Mahony\",\"doi\":\"10.1016/j.toxlet.2025.07.050\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The HESI Developmental and Reproductive Toxicology (DART) Working Group of the Botanical Safety Consortium is dedicated to developing reliable screening strategies to identify botanicals with potential developmental or reproductive toxicity. Our mission encompasses the selection of <em>in silico</em> and <em>in vitro</em> tools capable of accommodating the complex mixtures inherent in botanicals, as well as the evaluation of candidate botanicals based on suspected DART endpoints. We have established a series of botanical case studies to assess the efficacy of a NAM toolbox based on functional as well mechanistic assays.</div><div>In our recent evaluations, we identified several botanicals that have been studied for DART effects. Blue cohosh (Caulophyllum thalictroides), traditionally used to induce labour, was associated with fetal bovine cardiac defects. Usnea Lichen affected estrous cycling in a 90-day rodent study, and usnic acid demonstrated teratogenic effects in rats and zebrafish. Conversely, ashwagandha, Asian ginseng, and milk thistle are not expected to cause DART effects.</div><div>Selected assays, such as Devtox Quick Predict and transcriptional profiling with Connectivity Mapping, were employed to explore their utility in identifying DART-relevant botanicals. Notably, the Devtox assay revealed significant changes in cystine and ornithine metabolism for blue cohosh and usnea lichen, indicating a high potential for developmental toxicity. Ginseng showed changes in cystine metabolism alone, and no response was detected with ashwagandha. Although milk thistle exhibited changes in both metabolites, these occurred at concentrations affecting cell viability. Connectivity Mapping (CMap) analysis linked blue cohosh to compounds like GABA receptor antagonists, acetylcholinesterase inhibitors, and mycophenolic acid, all of which are associated with adverse reproductive outcomes. Ginseng connections included ginsenosides and various agents with potential stimulating and hormonal effects.</div><div>The data generated from this research will be made publicly available via the NIEHS database. As we continue, we aim to refine our data analysis and expand our assays and botanical repertoire to enhance safety decision-making processes in botanical evaluation.</div></div>\",\"PeriodicalId\":23206,\"journal\":{\"name\":\"Toxicology letters\",\"volume\":\"411 \",\"pages\":\"Page S16\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378427425016339\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378427425016339","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

植物安全联盟的HESI发育和生殖毒理学（DART）工作组致力于开发可靠的筛选策略，以识别具有潜在发育或生殖毒性的植物药物。我们的任务包括选择能够容纳植物药物固有的复杂混合物的硅和体外工具，以及基于可疑DART终点的候选植物药物评估。我们建立了一系列植物学案例研究，以评估基于功能和机制分析的不结盟运动工具箱的功效。在我们最近的评估中，我们确定了几种已经研究过DART效果的植物药。蓝升麻（Caulophyllum thalictroides），传统上用于引产，与胎牛心脏缺陷有关。在一项为期90天的啮齿动物研究中，Usnea Lichen影响了动情周期，usnic酸在大鼠和斑马鱼中显示出致畸作用。相反，ashwagandha，亚洲人参和水飞蓟预计不会引起DART效应。选定的分析方法，如Devtox快速预测和连接图谱转录分析，被用来探索它们在识别dart相关植物中的效用。值得注意的是，Devtox实验显示蓝升麻和usnea地衣的胱氨酸和鸟氨酸代谢发生了显著变化，表明其具有很高的发育毒性。人参单独对胱氨酸代谢有影响，而与ashwagandha联合用药对胱氨酸代谢无影响。尽管水飞蓟表现出两种代谢物的变化，但这些变化发生在影响细胞活力的浓度下。连接图谱（CMap）分析将蓝升麻与GABA受体拮抗剂、乙酰胆碱酯酶抑制剂和霉酚酸等化合物联系起来，所有这些化合物都与不利的生殖结果有关。人参连接物包括人参皂苷和各种具有潜在刺激和激素作用的物质。这项研究产生的数据将通过NIEHS数据库公开提供。随着我们的继续，我们的目标是完善我们的数据分析，扩大我们的分析和植物库，以加强植物评估的安全决策过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

S03-01 An emerging toolbox for Botanical risk assessment

The HESI Developmental and Reproductive Toxicology (DART) Working Group of the Botanical Safety Consortium is dedicated to developing reliable screening strategies to identify botanicals with potential developmental or reproductive toxicity. Our mission encompasses the selection of in silico and in vitro tools capable of accommodating the complex mixtures inherent in botanicals, as well as the evaluation of candidate botanicals based on suspected DART endpoints. We have established a series of botanical case studies to assess the efficacy of a NAM toolbox based on functional as well mechanistic assays.

In our recent evaluations, we identified several botanicals that have been studied for DART effects. Blue cohosh (Caulophyllum thalictroides), traditionally used to induce labour, was associated with fetal bovine cardiac defects. Usnea Lichen affected estrous cycling in a 90-day rodent study, and usnic acid demonstrated teratogenic effects in rats and zebrafish. Conversely, ashwagandha, Asian ginseng, and milk thistle are not expected to cause DART effects.

Selected assays, such as Devtox Quick Predict and transcriptional profiling with Connectivity Mapping, were employed to explore their utility in identifying DART-relevant botanicals. Notably, the Devtox assay revealed significant changes in cystine and ornithine metabolism for blue cohosh and usnea lichen, indicating a high potential for developmental toxicity. Ginseng showed changes in cystine metabolism alone, and no response was detected with ashwagandha. Although milk thistle exhibited changes in both metabolites, these occurred at concentrations affecting cell viability. Connectivity Mapping (CMap) analysis linked blue cohosh to compounds like GABA receptor antagonists, acetylcholinesterase inhibitors, and mycophenolic acid, all of which are associated with adverse reproductive outcomes. Ginseng connections included ginsenosides and various agents with potential stimulating and hormonal effects.

The data generated from this research will be made publicly available via the NIEHS database. As we continue, we aim to refine our data analysis and expand our assays and botanical repertoire to enhance safety decision-making processes in botanical evaluation.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊