The aim of our study was the detailed polyphenol profiling of Juglans nigra and the
characterization of the membrane permeability and antiproliferative properties of
its main phenolics. A total of 161 compounds were tentatively identified in J. nigra
bark, leaf, and pericarp extracts by ultrahigh-performance liquid chromatography–high-resolution
tandem mass spectrometry (UHPLC-HR-MS/MS). Eight compounds including myricetin-3-O-rhamnoside
(86), quercetin-3-O-rhamnoside (106), quercetin-3-O-xyloside (74), juglone (141),
1,2,3,4-tetrahydro-7,8-dihydroxy-4-oxonaphthalen-1-yl-6-O-galloyl-glucoside (92),
ellagic acid (143), gallic acid (14), and ethyl gallate (58) were isolated from J.
nigra pericarp. The in vitro antiproliferative activity of the isolated compounds
was investigated against three human cancer cell lines, confirming that juglone (141)
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 (141) and ethyl-gallate (58) showed positive results in the blood–brain-barrier-specific
PAMPA-BBB study. Juglone (141) also possesses logPe values which indicates that it
may be able to cross both the GI and BBB membranes via passive diffusion.
