Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal.
Chemistry Research Centre-Vila Real (CQ-VR), Food and Wine Chemistry Laboratory, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal.
Int J Mol Sci. 2024 May 14;25(10):5343. doi: 10.3390/ijms25105343.
Natural products are generally considered safe for human consumption, but this classification is often based on ethnobotanical surveys or their use in traditional medicine over a long period of time. However, edaphoclimatic factors are known to produce different chemotypes, which may affect the safety profile and bioactivities, and are not commonly considered for plants exploited as crops worldwide. Boiss., a thyme species with various health-promoting effects, has potential pharmaceutical applications, but edaphoclimatic factors were found to significantly impact its phytochemical composition. Thus, we aimed to assess the safety profile of extracts obtained from plants harvested in two locations over three consecutive years and to establish an association with specific components, an essential study in the search for new sources of nutraceuticals. Thus, the antiproliferative effect of an aqueous decoction (AD), hydroethanolic (HE) extracts, and major extracts' components of was evaluated on intestinal (Caco-2) and hepatic (HepG2) cell models, revealing effects dependent on extract type, cell line, and tested compounds. Flavonoids induced different cytotoxic patterns, which could be attributed to molecular structural differences. Flow cytometry analysis showed apoptosis and necrosis induction, mediated by the modulation of intracellular reactive oxygen species and mitochondrial membrane potential, effects that were dependent on the cell line and phytochemical composition and on the synergism between extracts components, rather than on the activity of an isolated compound. While ursolic acid was the component with the strongest impact on the difference between extraction methods, flavonoids assumed a pivotal role in the response of different cell lines to the extracts. We report for the first time, for spp. extracts, that variations in the phytochemical composition clearly influence the cellular response, thus highlighting the need for extract standardization for medicinal applications.
天然产物通常被认为对人类食用安全，但这种分类通常基于民族植物学调查或它们在传统医学中的长期使用。然而，土壤气候因素已知会产生不同的化学型，这可能会影响安全性概况和生物活性，而这些因素通常不被认为是全球范围内作为作物开发的植物的特征。百里香属植物是一种具有多种促进健康作用的植物，具有潜在的药用应用，但土壤气候因素被发现会显著影响其植物化学成分。因此，我们旨在评估在三年内从两个地点收获的植物中提取的提取物的安全性概况，并与特定成分建立关联，这是寻找新的营养保健品来源的必要研究。因此，评估了水浸液（AD）、水醇（HE）提取物和 的主要提取物成分对肠道（Caco-2）和肝脏（HepG2）细胞模型的增殖抑制作用，结果表明，提取物类型、细胞系和测试化合物的不同，其效果也不同。类黄酮诱导了不同的细胞毒性模式，这可能归因于分子结构的差异。流式细胞术分析表明，细胞凋亡和坏死的诱导是通过调节细胞内活性氧和线粒体膜电位介导的，这些作用取决于细胞系和植物化学成分以及提取物成分之间的协同作用，而不是依赖于单一化合物的活性。虽然熊果酸是对不同提取方法差异影响最大的成分，但类黄酮在不同细胞系对提取物的反应中起着关键作用。我们首次报道了百里香属植物提取物，植物化学成分的变化明显影响细胞反应，因此强调了为药用应用进行提取物标准化的必要性。
