Blood-brain barrier specific permeability assay reveals N-methylated tyramine derivatives in standardised leaf extracts and herbal products of Ginkgo biloba.
The linkage between the central nervous system availability and neuropharmacological activity of the constituents of Ginkgo biloba L. extracts (GBE) is still incomplete. In this study, the in vitro blood-brain barrier (BBB) permeability profile of the standardised GBE was investigated by the parallel artificial membrane permeability assay (PAMPA). Biomarkers, such as terpene trilactones, flavonoid aglycones and ginkgotoxin exerted moderate or good BBB-permeability potential (BBB+), while glycosides and biflavones were predicted as unable to pass the BBB. N-methyltyramine (NMT) and N,N-dimethyltyramine or hordenine (Hor) were identified among BBB+ compounds, while subsequent direct HRMS analysis revealed tyramine (Tyr) and N,N,N-trimethyltyramine or candicine (Can) in GBE as trace constituents. Distribution of Tyr, NMT, Hor and Can was determined by a validated ion-exchange mechanism-based liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method in G. biloba samples, such as herbal drugs and dietary supplements. The total content of the four tyramine derivatives in various GBEs ranged from 7.3 up to 6357μg/g dry extract with NMT and Hor as most abundant ones. Considering the pharmacological activities and the revealed fluctuation in the concentration of the analysed adrenergic protoalkaloids, the presented rapid LC-ESI-MS method is proposed for monitoring of the levels of Tyr, NMT, Hor and Can in G. biloba products.
Compound Profiling Laboratory, Gedeon Richter Plc., Gyömrői u. 19-21., H-1475 Budapest, Hungary.
Árpád
Á
Könczöl
Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
Kata
K
Rendes
Spectroscopic Research, Gedeon Richter Plc., Gyömrői u. 19-21., H-1475 Budapest, Hungary.
Miklós
M
Dékány
Compound Profiling Laboratory, Gedeon Richter Plc., Gyömrői u. 19-21., H-1475 Budapest, Hungary.
Judit
J
Müller
Compound Profiling Laboratory, Gedeon Richter Plc., Gyömrői u. 19-21., H-1475 Budapest, Hungary.
Eszter
E
Riethmüller
Compound Profiling Laboratory, Gedeon Richter Plc., Gyömrői u. 19-21., H-1475 Budapest, Hungary. Electronic address: gytbalogh@gmail.com.
György Tibor
GT
Balogh
D000470:Alkaloids / Q000032:analysis; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D020441:Ginkgo biloba / Q000737:chemistry*; D008567:Membranes, Artificial; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics*; D018515:Plant Leaves / Q000737:chemistry; D028321:Plant Preparations / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D014439:Tyramine / Q000031:analogs & derivatives / Q000032:analysis / Q000493:pharmacokinetics*
D000470:Alkaloids; D008567:Membranes, Artificial; D010936:Plant Extracts; D028321:Plant Preparations; C432454:candicine; C036244:methyl-4-tyramine; C007964:hordenine; D014439:Tyramine
Blood-brain barrier permeability; Candicine; Ginkgo biloba; Hordenine; LC–MS; N-methyltyramine; PAMPA; Tyramine