Li Min, Li Wenying, Xu Fang, Pu Yiping, Li Jianguang
College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China.
Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Xinjiang Medical University, Urumqi 830011, China.
Pharmaceutics. 2024 Dec 2;16(12):1543. doi: 10.3390/pharmaceutics16121543.
, an active component of Arnebia euchroma (Royle) Johnst., has remarkable pharmacological effects, particularly in its anti-tumour activity. Nonetheless, the specific targets and mechanisms of action remain to be further explored. A novel FeO@ was designed and synthesized in this study by linking FeO and through benzophenone. FeO@ was characterized using several techniques, including scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), and drug removal methods, to determine the content of on the surface of the magnetic particles. Target hooking technology was utilized to identify the target proteins of the compound in melanoma. The synthesized FeO@ was co-incubated with A375 cell lysate, followed by the target proteins, which were purified by magnetic enrichment using magnetic microspheres and identified by high-resolution mass spectrometry. AutoDock Vina software was employed for molecular docking analysis, where it was found that targets RPN1, CPEB4, and HNRNPUL1 proteins. Subsequently, A375 cells were treated with at different concentrations (2.5, 5.0, 10.0 μM) for 48 h, and the expressions of the three proteins were observed. The results showed a significant reduction in the relative expression of CPEB4 in the high-dose group compared to the control group ( < 0.01). Moreover, the relative expression of HNRNPUL1 was decreased in the medium- and high-dose groups ( < 0.05). This study initially revealed from the source that may regulate melanoma-specific markers, melanosomes, tyrosine kinases related to abnormal tyrosine metabolism, and melanoma through multiple targets such as CPEB4 and HNRNPUL1. Proliferation and metastasis work together to exert an anti-melanoma mechanism, which provides a new idea for the follow-up study of the molecular pharmacological mechanism of the complex system of total naphthoquinones in (Royle) Johns.
紫草素是新疆紫草（Royle）Johnst.的一种活性成分，具有显著的药理作用，尤其是在抗肿瘤活性方面。然而，其具体靶点和作用机制仍有待进一步探索。本研究通过二苯甲酮将FeO与[具体物质]连接，设计并合成了一种新型的FeO@[具体物质]。采用扫描电子显微镜（SEM）、傅里叶变换红外光谱（FT-IR）和药物去除方法等多种技术对FeO@[具体物质]进行表征，以确定磁性颗粒表面[具体物质]的含量。利用靶标钩技术鉴定该化合物在黑色素瘤中的靶蛋白。将合成的FeO@[具体物质]与A375细胞裂解液共同孵育，随后通过磁性微球进行磁性富集纯化靶蛋白，并通过高分辨率质谱进行鉴定。使用AutoDock Vina软件进行分子对接分析，发现[具体物质]靶向RPN1、CPEB4和HNRNPUL1蛋白。随后，用不同浓度（2.5、5.0、10.0 μM）的[具体物质]处理A375细胞48小时，观察这三种蛋白的表达情况。结果显示，高剂量组中CPEB4的相对表达量与对照组相比显著降低（P<0.01）。此外，中剂量和高剂量组中HNRNPUL1的相对表达量降低（P<0.05）。本研究初步从源头揭示[具体物质]可能通过CPEB4和HNRNPUL1等多个靶点调节黑色素瘤特异性标志物、黑素小体、与异常酪氨酸代谢相关的酪氨酸激酶以及黑色素瘤。增殖和转移共同发挥抗黑色素瘤机制，为新疆紫草（Royle）Johnst.中总萘醌复合体系分子药理机制的后续研究提供了新思路。
