College of Chinese Medicinal Material, Jilin Agricultural University, Xincheng Street No. 2888, Changchun Shi, Jilin province, 130118, China.
Sci Rep. 2018 Feb 19;8(1):3307. doi: 10.1038/s41598-018-21722-1.
Arctigenin (ARG) is a functional active component that has important physiological and pharmacological activities. The anti-tumour and anti-inflammatory activities of ARG show good potential for application and development, but this material has the defect of low water solubility. In this experiment, the valine derivative of ARG (ARG-V) was designed and synthesized to overcome this disadvantage. The ARG amino acid, EDCI and DMAP were raw materials in the addition reaction, with a molar ratio of 1:2:2:0.5. The yield of ARG-V was up to 80%. ARG-V has strong anti-tumour activity in vivo and in vitro. The inhibitory rate of ARG-V was 69.2%, with less damage to the immune organs and different degrees of increased serum cytotoxicity. Moreover, the pharmacokinetics of ARG following oral administration and ARG-V following oral administration in rats were also studied. The C and AUC values of ARG-V showed significant differences compared to ARG. The relative bioavailabilities of three doses of ARG-V compared to ARG were 664.7%, 741.5% and 812.9%. These pharmacokinetic results may be useful for further studies of the bioactive mechanism of ARG and provide a theoretical basic for clinical use.
牛蒡子苷元（ARG）是一种具有重要生理和药理活性的功能活性成分。ARG 的抗肿瘤和抗炎活性显示出良好的应用和开发潜力，但该物质具有水溶性低的缺点。在本实验中，设计并合成了 ARG 的缬氨酸衍生物（ARG-V）以克服这一缺点。ARG 氨基酸、EDCI 和 DMAP 是加成反应的原料，摩尔比为 1:2:2:0.5。ARG-V 的产率高达 80%。ARG-V 在体内和体外均具有很强的抗肿瘤活性。ARG-V 的抑制率为 69.2%，对免疫器官的损伤较小，并在不同程度上增加了细胞毒性。此外，还研究了大鼠口服 ARG 和口服 ARG-V 的药代动力学。与 ARG 相比，ARG-V 的 C 和 AUC 值有显著差异。与 ARG 相比，ARG-V 三个剂量的相对生物利用度分别为 664.7%、741.5%和 812.9%。这些药代动力学结果可能有助于进一步研究 ARG 的生物活性机制，并为临床应用提供理论基础。
