Influence of the St John´s wort extract Ze117 and selected ingredients on membrane fluidity and phospholipid composition in rat C6 glioblastoma cells

Abstract

Chronic stress has been recognized to represent a key factor for the development of depression. Among others cortisol has been described to mediate an adaptive effect on plasma membrane fluidity which may affect signal transduction of membrane-bound receptors and contribute to pathophysiological changes leading to depression.<br /> Membrane fluidity can be measured by fluorescence anisotropy using DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH (1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene). While chronic incubation (6-8 days) with terbutaline or dobutamine did not affect membrane fluidity of C6 cells, chronic exposure to cortisol dose-dependently decreased DPH and TMA-DPH fluorescence anisotropy, reflecting an increase in membrane fluidity. In contrast, cells pretreated with St. John's wort extract Ze117 showed increased DPH and TMA-DPH fluorescence anisotropy values, indicating a membrane rigidification effect which was mediated at least by the constituents hypericin, hyperforin, quercetin, amentoflavone and biapigenin. Rutin showed no effect. The tricyclic antidepressant desipramine (DMI) also showed to expose an adaptive decrease in membrane fluidity, however, only in the membrane core as measured by increased DPH fluorescence anisotropy. Chronic incubation with citalopram on the other side exposed no impact on membrane fluidity. Therefore it can be assumed that Ze117, and in part DMI, have a "normalizing" effect on the membrane fluidity of "stressed" cells. <br /> Focusing on underlying lipidomic changes a decrease of the phosphatidylcholine to phosphatidylethanolamine (PC/PE) ratio was found in whole cell lipid extracts after chronic cortisol and Ze117 exposure which resulted at least in part from a decreased PC de-novo synthesis. In contrast to cortisol, which mediated a nonsignificant small decreased incorporation of choline-D9 into all main PC species under investigation, chronic Ze117 incubation selectively inhibited the synthesis of PC species bearing saturated or monounsaturated fatty acids. <br /> Citalopram and DMI had no impact on the PC/PE ratio and the choline-D9 incorporation rate.