Ocotea fasciculata presents yangambin (YAN) and its isomer epi-yangambin (EPI-YAN) as major lignans, which are employed as the plant markers for quality control purposes and as potential pharmacological compounds. However, a gap between the pure isomers and safety and efficacy protocols is faced by the scientific community. In this context, this work aimed to report (i) a new and advantageous purifying process in a semi-preparative scale for YAN and EPI-YAN isolation from Ocotea fasciculata, and (ii) an in vitro cytotoxicity study to estimate, for the first time, the LD50 values of the isolated epimers, as well as the influence of albumin concentration in cell culture medium. The best condition for epimers isolation was achieved in normal-phase liquid chromatography. The lignan fraction (LF), previously obtained from the plant ethanolic extract, was purified yielding 17% and 29% of YAN and EPI-YAN, respectively. The in vitro study demonstrated that YAN and EPI-YAN were safe, and only at the highest concentration studied, a decrease on cell viability was observed. The estimated LD50 value was higher than 1612 mg/kg for both epimers. The LF, on the other hand, demonstrated an estimated LD50 of 422 mg/kg. Lignan cytotoxicity studies also evidenced that the higher cell viability was related to the higher concentration of fetal bovine serum as a source of albumin in medium. This is the first time the LD50 and safety of the isolated epimers were estimated, opening up great perspectives of success in in vivo studies.

中文翻译：

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Yangambin 和 Epi-yangambin 异构体：来自 Ocotea fasciculata 的新纯化方法和关注体内安全性的第一个细胞毒性方面

Ocotea fasciculata 将杨甘素 (YAN) 及其异构体表杨木素 (EPI-YAN) 作为主要木脂素，用作质量控制目的的植物标记物和潜在的药理化合物。然而，科学界面临着纯异构体与安全性和有效性协议之间的差距。在此背景下，这项工作旨在报告 (i) 从 Ocotea fasciculata 中分离 YAN 和 EPI-YAN 的半制备规模的新型有利纯化工艺，以及 (ii) 一项用于估计的体外细胞毒性研究，这是首次时间，分离的差向异构体的 LD50 值，以及细胞培养基中白蛋白浓度的影响。在正相液相色谱中实现了差向异构体分离的最佳条件。木酚素部分 (LF)，以前从植物乙醇提取物中获得，纯化后分别产生 17% 和 29% 的 YAN 和 EPI-YAN。体外研究表明 YAN 和 EPI-YAN 是安全的，只有在研究的最高浓度下，才观察到细胞活力下降。两种差向异构体的估计 LD50 值均高于 1612 mg/kg。另一方面，LF 显示估计的 LD50 为 422 mg/kg。木脂素细胞毒性研究还证明，较高的细胞活力与较高浓度的胎牛血清作为培养基中白蛋白的来源有关。这是首次估计分离的差向异构体的 LD50 和安全性，为体内研究的成功开辟了广阔的前景。观察到细胞活力降低。两种差向异构体的估计 LD50 值均高于 1612 mg/kg。另一方面，LF 表明估计的 LD50 为 422 mg/kg。木脂素细胞毒性研究还证明，较高的细胞活力与较高浓度的胎牛血清作为培养基中白蛋白的来源有关。这是首次估计分离的差向异构体的 LD50 和安全性，为体内研究的成功开辟了广阔的前景。观察到细胞活力降低。两种差向异构体的估计 LD50 值均高于 1612 mg/kg。另一方面，LF 表明估计的 LD50 为 422 mg/kg。木脂素细胞毒性研究还证明，较高的细胞活力与较高浓度的胎牛血清作为培养基中白蛋白的来源有关。这是首次估计分离的差向异构体的 LD50 和安全性，为体内研究的成功开辟了广阔的前景。