Dataset Information

Impact of St. John's wort extract Ze 117 on stress induced changes in the lipidome of PBMC.

ABSTRACT:

Background

Membrane lipids have an important function in the brain as they not only provide a physical barrier segregating the inner and outer cellular environments, but are also involved in cell signaling. It has been shown that the lipid composition effects membrane fluidity which affects lateral mobility and activity of membrane-bound receptors.

Methods

Since changes in cellular membrane properties are considered to play an important role in the development of depression, the effect of St. John's wort extract Ze 117 on plasma membrane fluidity in peripheral blood mononuclear cells (PBMC) was investigated using fluorescence anisotropy measurements. Changes in fatty acid residues in phospholipids after treatment of cortisol-stressed [1 μM] PBMCs with Ze 117 [10-50 µg/ml] were analyzed by mass spectrometry.

Results

Cortisol increased membrane fluidity significantly by 3%, co-treatment with Ze 117 [50 µg/ml] counteracted this by 4.6%. The increased membrane rigidity by Ze 117 in cortisol-stressed [1 μM] PBMC can be explained by a reduced average number of double bonds and shortened chain length of fatty acid residues in phospholipids, as shown by lipidomics experiments.

Conclusion

The increase in membrane rigidity after Ze 117 treatment and therefore the ability to normalize membrane structure points to a new mechanism of antidepressant action of the extract.

SUBMITTER: Bussmann H

PROVIDER: S-EPMC10082490 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Impact of St. John's wort extract Ze 117 on stress induced changes in the lipidome of PBMC.

Bussmann Hendrik H Bremer Swen S Häberlein Hanns H Boonen Georg G Drewe Jürgen J Butterweck Veronika V Franken Sebastian S

Molecular medicine (Cambridge, Mass.) 20230407 1

<h4>Background</h4>Membrane lipids have an important function in the brain as they not only provide a physical barrier segregating the inner and outer cellular environments, but are also involved in cell signaling. It has been shown that the lipid composition effects membrane fluidity which affects lateral mobility and activity of membrane-bound receptors.<h4>Methods</h4>Since changes in cellular membrane properties are considered to play an important role in the development of depression, the e ...[more]

PMID: 37029349

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Project description:Chronic stress is a key factor in the development of depression. It leads to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, which in turn increases the formation of glucocorticoids (GCs). Chronically elevated GC levels disrupt neuroplasticity and affect brain lipid metabolism, which may, ultimately, contribute to the development of depression. This study aimed to investigate the effects of the antidepressants St. John's Wort extract and escitalopram on lipid metabolism in vivo. Therefore, repeated corticosterone injections were used to induce depression-like behavior in rats. Male Sprague-Dawley rats were stressed with corticosterone injections (40 mg/kg, s.c.) over 22 consecutive days and were concomitantly treated with varying doses of the St. John's wort extract Ze 117 (30, 90 or 180 mg/kg, p.o.) or escitalopram (10 mg/kg, p.o.) and behavioral changes were evaluated using a modified forced swim test. The results indicate that repeated corticosterone injections significantly decreased the latency to first immobility. Furthermore, co-treatment of corticosterone with Ze 117 increased latency to first immobility significantly compared to rats treated with corticosterone alone. To further investigate the biochemical effects of corticosterone-induced stress, as well as the possible counter-regulation by antidepressants, the lipidomes of the plasma and hippocampus samples were analyzed by shotgun mass spectrometry. Corticosterone-induced stress significantly altered key lipid metabolites in the plasma but not in the hippocampal samples. In the hippocampus, however, specific glycerophospholipids such as lysophosphatidylethanolamines (LPEs) increased with escitalopram treatment and with Ze 117, both showing significant correlations with behavioral parameters. In summary, our study shows significant behavioral- and lipidome-altering processes with Ze 117 and escitalopram in rat plasma and hippocampal samples, thereby providing new targets and biomarker ideas for clinical diagnosis and antidepressant intervention.

Project description:BackgroundIn some countries extracts of the plant Hypericum perforatum L. (popularly called St. John's wort) are widely used for treating patients with depressive symptoms.ObjectivesTo investigate whether extracts of hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of major depression; and whether they have fewer adverse effects than standard antidepressant drugs.Search strategyTrials were searched in computerised databases, by checking bibliographies of relevant articles, and by contacting manufacturers and researchers.Selection criteriaTrials were included if they: (1) were randomised and double-blind; (2) included patients with major depression; (3) compared extracts of St. John's wort with placebo or standard antidepressants; (4) included clinical outcomes assessing depressive symptoms.Data collection and analysisAt least two independent reviewers extracted information from study reports. The main outcome measure for assessing effectiveness was the responder rate ratio (the relative risk of having a response to treatment). The main outcome measure for adverse effects was the number of patients dropping out due to adverse effects.Main resultsA total of 29 trials (5489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28 (95% confidence interval (CI), 1.10 to 1.49) and from nine smaller trials was 1.87 (95% CI, 1.22 to 2.87). Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 (95% CI, 0.90 to 1.15; 5 trials) and 1.00 (95% CI, 0.90 to 1.11; 12 trials). Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum. Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (odds ratio (OR) 0.24; 95% CI, 0.13 to 0.46) or SSRIs (OR 0.53, 95% CI, 0.34-0.83).Authors' conclusionsThe available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

Project description:The plant St. John's wort contains high levels of melatonin, an important biochemical that has both beneficial and adverse effects on stress. Therefore, a method for increasing melatonin levels in plants without adversely affecting their growth is economically important. In this study, we investigated the regulation of melatonin levels in St. John's wort by exposing samples to salinity stress (150 mM) and salicylic acid (0.25 mM) to augment stress tolerance. The results indicated that salinity stress significantly reduced the plant chlorophyll content and damaged the photosystem, plant growth and development. Additionally, these were reconfirmed with biochemical indicators; the levels of abscisic acid (ABA) and proline were increased and the activities of antioxidants were reduced. However, a significant increase was found in melatonin content under salinity stress through upregulation in the relative expression of tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), serotonin N-acetyltransferase (SNAT), and N-acetylserotonin methyltransferase (ASMT). The salicylic acid (SA) treatment considerably improved their photosynthetic activity, the maximum photochemical quantum yield (133%), the potential activity of PSⅡ (294%), and the performance index of electron flux to the final PS I electron acceptors (2.4%). On the other hand, SA application reduced ABA levels (32%); enhanced the activity of antioxidant enzymes, such as superoxide dismutase (SOD) (15.4%) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (120%); and increased polyphenol (6.4%) and flavonoid (75.4%) levels in salinity-stressed St. John's wort plants. Similarly, SA application under NaCl stress significantly modulated the melatonin content in terms of ion balance; the level of melatonin was reduced after SA application on salt-treated seedlings but noticeably higher than on only SA-treated and non-treated seedlings. Moreover, the proline content was reduced considerably and growth parameters, such as plant biomass, shoot length, and chlorophyll content, were enhanced following treatment of salinity-stressed St. John's wort plants with salicylic acid. These findings demonstrate the beneficial impact of salt stress in terms of a cost-effective approach to extract melatonin in larger quantities from St. John's wort. They also suggest the efficiency of salicylic acid in alleviating stress tolerance and promoting growth of St. John's wort plants.

Project description:Introduction: Since ancient times Hypericum perforatum L. named St. John's wort (SJW), has been used in the management of a wide range of applications, including nervous disorders. Development of mood disorders are due to alterations in glutamate metabolism, initiation of inflammatory pathways, and changes of the neuronal plasticity. Previous studies suggest that the glutamatergic system contributes to the pathophysiology of depression. Extracts of SJW have been recommended for the treatment of depression. The aim of the present in vitro study was to evaluate the action of STW3-VI, a special SJW extract in differentiated mouse hippocampal HT-22 neurons. We evaluated the stimulation of neurogenesis, the protective effect against glutamate or N-methyl-D-aspartate receptor induced-excitotoxicity and its anti-inflammatory properties in LPS-activated human macrophages. Results: After 48 h treatment, STW3-VI stimulated the neurite formation by 25% in comparison with the control and showed protective effects against glutamate- or NMDA-induced cytotoxicity by significantly increasing the viability about +25 or +50%. In conjunction with these effects, after pretreatment with STW3-VI, the intracellular reduced glutathione content was significantly 2.3-fold increased compared with the neurons incubated with glutamate alone. Additionally, pre-treatment of human macrophages with STW3-VI showed anti-inflammatory effects after 24 or 48 h concerning inhibition of LPS-induced TNF release by -47.3 and -53.8% (24 h) or -25.0 to -64.8% (48 h). Conclusions: Our data provide new evidence that STW3-VI protects hippocampal cells from NMDA- or glutamate-induced cytotoxicity. Moreover, our results indicate a morphological remodeling by increasing neurite outgrowth and activation of the anti-inflammatory defense by inhibition of the cytokine production in human macrophages after STW3-VI treatment. These protective, neurotrophic and anti-inflammatory properties may be beneficial in the treatment of depressive disorders.

Project description:BackgroundSt. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA.MethodsEight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.ResultsOf the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0-8) for 23.9% completeness.ConclusionThe vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.

Dataset Information

Impact of St. John's wort extract Ze 117 on stress induced changes in the lipidome of PBMC.

Background

Methods

Results

Conclusion

Publications

Impact of St. John's wort extract Ze 117 on stress induced changes in the lipidome of PBMC.

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