Membrane Permeability and Aqueous Stability Study of Linear and Cyclic Diarylheptanoids from Corylus maxima

Abstract

Seven diarylheptanoids were isolated from Corylus maxima by flash chromatography and semipreparative high-performance liquid chromatography (HPLC) and identified by Orbitrap® mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy as linear diarylheptanoids: hirsutanonol-5-O-β-D-glucopyranoside (1), platyphyllonol-5-O-β-D-xylopyranoside (4), platyphyllenone (5); and cyclic derivatives: alnusonol-11-O-β-D-glucopyranoside (6), alnusone (7), giffonin F (8), carpinontriol B (9). Cyclic diarylheptanoids are reported in C. maxima for the first time. The aqueous stability of the isolated compounds and other characteristic constituents of C. maxima, oregonin (2), hirsutenone (3), quercitrin (10) and myricitrin (11) was evaluated at pH 1.2, 6.8 and 7.4. The passive diffusion of the constituents across biological membranes was investigated by parallel artificial membrane permeability assay for the gastrointestinal tract (PAMPA-GI) and the blood–brain barrier (PAMPA-BBB) methods. The cyclic diarylheptanoid aglycones and quercitrin were stable at all investigated pH values, while a pH-dependent degradation of the other compounds was observed. A validated ultrahigh-performance liquid chromatography-diode-array detection (UHPLC-DAD) method was utilized for the determination of compound concentrations. The structures of the degradation products were characterized by UHPLC-Orbitrap® MS. Platyphyllenone and alnusone possessed log Pe values greater than −5.0 and −6.0 in the PAMPA-GI and PAMPA-BBB studies, respectively, indicating their ability to cross the membranes via passive diffusion. However, only alnusone can be considered to have both good aqueous stability and satisfactory membrane penetration ability.