关键词: Thymus carnosus Boiss. apoptosis cell cycle arrest cytotoxicity mitochondrial membrane potential necrosis phytochemicals reactive oxygen species

Mesh : Thymus Plant / chemistry Humans Plant Extracts / pharmacology chemistry Oxidative Stress / drug effects Phytochemicals / pharmacology chemistry analysis Caco-2 Cells Hep G2 Cells Apoptosis / drug effects Cell Proliferation / drug effects Cell Death / drug effects Reactive Oxygen Species / metabolism Flavonoids / pharmacology chemistry analysis Biomarkers

来  源:   DOI:10.3390/ijms25105343   PDF(Pubmed)

Abstract:
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. Thymus carnosus 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 T. carnosus 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 T. carnosus 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 Thymus spp. extracts, that variations in the phytochemical composition clearly influence the cellular response, thus highlighting the need for extract standardization for medicinal applications.
摘要:
天然产品通常被认为对人类食用是安全的,但是这种分类通常是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,众所周知,气源因子会产生不同的化学型,这可能会影响安全性和生物活性,并且通常不被认为是全球范围内用作农作物的植物。胸腺肉麻Boiss.,一种具有各种健康促进作用的百里香,具有潜在的制药应用,但发现了植物营养因子对其植物化学成分的影响。因此,我们旨在评估连续三年从两个地点收获的植物中获得的T.carnosus提取物的安全性,并建立与特定成分的关联,寻找新的营养品来源的一项重要研究。因此,水煎剂(AD)的抗增殖作用,乙醇(HE)提取物,在肠(Caco-2)和肝(HepG2)细胞模型上评估了马氏杆菌的主要提取物成分,揭示依赖于提取物类型的影响,细胞系,和测试的化合物。黄酮类化合物诱导不同的细胞毒性模式,这可能归因于分子结构的差异。流式细胞术分析显示凋亡和坏死诱导,通过调节细胞内活性氧和线粒体膜电位,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,而不是分离化合物的活性。而熊果酸是对提取方法差异影响最大的成分,类黄酮在不同细胞系对提取物的反应中起着关键作用。我们第一次报道,为胸腺。摘录,植物化学成分的变化明显影响细胞反应,从而突出了药物应用的提取物标准化的需要。
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