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

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 P e 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.