Department of Animal Biotechnology, Institute of Tropical Biology, Vietnam Academy of Science and Technology, Ho Chi Minh City, Vietnam.
Faculty of Biotechnology, Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Ha Noi City, Vietnam.
J Toxicol Environ Health A. 2021 Dec 17;84(24):987-1003. doi: 10.1080/15287394.2021.1963363. Epub 2021 Aug 12.
Lind. () has promising anti-oxidant, hyperglycemic, hepatoprotective, and immunomodulatory activities as well as anti-tumor effects. However, the pharmacological actions of cultured plants remain to be determined. Therefore, the objective of the study was to assess cytotoxicity and potential toxicity of an extract derived from cultivated , termed as iARE. The total flavonoid content and predominant flavonoid compounds of extract were identified and quantitatively analyzed. cytotoxicity of iARE was examined using several cancer and normal cell lines. The apoptotic activity and expression of apoptosis-associated genes were also examined in MCF7 cells to determine the underlying mechanisms related to anti-proliferative effects. potential toxicity of iARE was assessed following acute and subchronic oral administration in Sprague Dawley rats. Quercetin, kaempferol, and isorhamnetin were three flavonoid components identified in iARE. The extract exerted cytotoxic effects on various cancer cells but not normal fibroblasts. Apoptosis in MCF7 cells was induced by iARE in a concentration-dependent manner associated with increased Bax/Bcl-2 ratio and reduced mitochondrial membrane potential ΔΨm, leading to release of cytochrome c, activation of caspase-3/7 and caspase-9, and cleavage of PARP. In the acute oral toxicity study, no mortality or toxicological signs were observed in rats at 1000 or 5000 mg/kg. In a subchronic oral toxicity study, iARE at a dosage of up to 1000 mg/kg produced no mortality or treatment-related adverse effects on general behavior, food intake, body weight, relative organ weights. No apparent marked changes in the histopathology of the liver and kidney were detected. Data demonstrated that iARE induced cytotoxic effects in cancer cells are associated with lackof toxicity. Thus, iARE was suggested to be considered as apotential therapeutic candidate for cancer treatment.
林德（Lind.）具有有前景的抗氧化、降血糖、保肝和免疫调节作用以及抗肿瘤作用。然而，培养植物的药理作用仍有待确定。因此，本研究的目的是评估从培养的中提取的提取物的细胞毒性和潜在毒性，称为 iARE。鉴定并定量分析了提取物的总类黄酮含量和主要类黄酮化合物。使用几种癌细胞和正常细胞系检查 iARE 的细胞毒性。还在 MCF7 细胞中检查了凋亡活性和凋亡相关基因的表达，以确定与抗增殖作用相关的潜在机制。通过急性和亚慢性口服给予 Sprague Dawley 大鼠来评估 iARE 的潜在毒性。在 iARE 中鉴定出三种类黄酮成分：槲皮素、山奈酚和异鼠李素。该提取物对各种癌细胞具有细胞毒性作用，但对正常成纤维细胞没有作用。iARE 以浓度依赖性方式诱导 MCF7 细胞凋亡，与 Bax/Bcl-2 比值增加和线粒体膜电位 ΔΨm 降低有关，导致细胞色素 c 释放、caspase-3/7 和 caspase-9 激活以及 PARP 裂解。在急性口服毒性研究中，1000 或 5000mg/kg 剂量的大鼠未观察到死亡率或毒性体征。在亚慢性口服毒性研究中，高达 1000mg/kg 的 iARE 未引起死亡率或与一般行为、食物摄入、体重、相对器官重量相关的治疗相关不良反应。未检测到肝脏和肾脏组织病理学的明显变化。数据表明，iARE 在癌细胞中诱导的细胞毒性作用与缺乏毒性有关。因此，iARE 被认为是癌症治疗的潜在治疗候选物。
