Department of Pharmacognosy, Semmelweis University, Üllői út 26, 1085 Budapest, Hungary.
Department Pharmaceutical Biology, Institute for Drug Discovery, University of Leipzig, Eilenburger Str. 14, 04317 Leipzig, Germany.
Int J Mol Sci. 2024 Jun 25;25(13):6930. doi: 10.3390/ijms25136930.
The aim of our study was the detailed polyphenol profiling of and the characterization of the membrane permeability and antiproliferative properties of its main phenolics. A total of 161 compounds were tentatively identified in bark, leaf, and pericarp extracts by ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HR-MS/MS). Eight compounds including myricetin-3--rhamnoside (), quercetin-3--rhamnoside (), quercetin-3--xyloside (), juglone (), 1,2,3,4-tetrahydro-7,8-dihydroxy-4-oxonaphthalen-1-yl-6--galloyl-glucoside (), ellagic acid (), gallic acid (), and ethyl gallate () were isolated from pericarp. The in vitro antiproliferative activity of the isolated compounds was investigated against three human cancer cell lines, confirming that juglone () inhibits cell proliferation in all of them, and has similar activity as the clinical standards. The permeability of the isolated compounds across biological membranes was evaluated by the parallel artificial membrane permeability assay (PAMPA). Both juglone () and ethyl-gallate () showed positive results in the blood-brain-barrier-specific PAMPA-BBB study. Juglone () also possesses log values which indicates that it may be able to cross both the GI and BBB membranes via passive diffusion.
我们研究的目的是详细分析 的多酚组成，并研究其主要酚类化合物的膜通透性和抗增殖特性。通过超高效液相色谱-高分辨串联质谱联用仪（UHPLC-HR-MS/MS）对 树皮、叶和果皮提取物中的 161 种化合物进行了初步鉴定。从 果皮中分离得到 8 种化合物，包括杨梅素-3--鼠李糖苷（）、槲皮素-3--鼠李糖苷（）、槲皮素-3--木糖苷（）、胡桃醌（）、1,2,3,4-四氢-7,8-二羟基-4-氧代萘-1-基-6--没食子酰基葡萄糖苷（）、鞣花酸（）、没食子酸（）和没食子酸乙酯（）。对分离得到的化合物进行了体外抗增殖活性研究，针对三种人癌细胞系，证实胡桃醌（）抑制所有细胞的增殖，其活性与临床标准相当。通过平行人工膜渗透率测定法（PAMPA）评估了分离化合物穿过生物膜的通透性。胡桃醌（）和没食子酸乙酯（）在血脑屏障特异性 PAMPA-BBB 研究中均呈阳性结果。胡桃醌（）还具有 log 值，这表明它可能能够通过被动扩散穿过 GI 和 BBB 膜。
