LC-MS characterization of terpene lactones in plasma of experimental animals treated with Ginkgo biloba extracts Correlation with pharmacological activity.
Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry (LC/APCI-ITMS) was applied to determine the concentration of terpene lactone in plasma of guinea pigs after chronic administration of Ginkgo biloba extract enriched in ginkgoterpenes in free form (IDN 5380) or complexed with soy phosphlipids (IDN 5381). Oral treatment of the animals with ginkgoterpenes resulted to inhibit the bronchoconstriction (ITP) and the concomitant increase of the levels of thromboxane B2 (TXB2) in the circulation caused by histamine (HIST) and platelet activating factor (PAF) in normal guinea pigs or by ovalbumin (OA) in actively sensitized guinea pigs. To compare the protective activities of G. biloba forms (IDN 5380 and IDN 5381), ED50 and dose ratio (DR) values for both parameters (ITP and TXB2) were evaluated. The phytosomic form (IDN 5381) significantly reduced (two- to four-fold as compared to free form, P < 0.001) the HIST, PAF or OA-induced airway changes and TXB2 release. In addition it has been observed that the absence of ginkgolide C (GC) in plasma samples (in human and animals) was due to its rapid methylation.
Mauri
Pierluigi
P
Istituto Tecnologie Biomediche, CNR, Via Fratelli Cervi, 93-20090 Segrate (Milan), Italy.
De Palma
Antonella
A
Pozzi
Francesca
F
Basilico
Fabrizio
F
Riva
Antonella
A
Morazzoni
Paolo
P
Bombardelli
Ezio
E
Rossoni
Giuseppe
G
D000328:Adult; D000818:Animals; D001682:Biological Availability; D016084:Bronchoconstriction / Q000187:drug effects; D002853:Chromatography, Liquid; D004224:Diterpenes / Q000097:blood; D020441:Ginkgo biloba / Q000737:chemistry*; D046934:Ginkgolides; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000097:blood; D008297:Male; D013058:Mass Spectrometry; D008958:Models, Molecular; D008968:Molecular Conformation; D010047:Ovalbumin / Q000494:pharmacology; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D013729:Terpenes / Q000097:blood* / Q000493:pharmacokinetics; D013929:Thromboxane B2 / Q000378:metabolism
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; D013729:Terpenes; C058295:ginkgolide C; D013929:Thromboxane B2; D006632:Histamine; D010047:Ovalbumin; C045856:ginkgolide B; C477042:ginkgolide A