ArticlePDF Available

Extrakte aus Griechischem Bergtee hemmen die Wiederaufnahme von Neurotransmittern

Authors:
  • Finzelberg GmbH & Co KG
  • Vivacell Biotechnology GmbH
Die oberirdischen Teile des Griechischen Bergtee´s (Herba Sideritis scardica) haben
im Europäischen Kulturkreis eine lange Tradition als Coffein-freier Tee zur
Entspannung nach der Arbeit [1].
Der Begriff Bergtee wurde jedoch historisch in verschiedenen Regionen parallel
benutzt, wobei ganz verschiedene Species von Herba Sidertis ssp. eingesetzt
wurden. Dies führte historisch zu Verwechslungen und letztendlich dem Beinahe-
Verlust an Wissen. So wurde nur regional das Wissen um die Sideritis-Tee´s
weitergegeben. Besonders in den bulgarischen Pirin-Bergen oder einzelnen
Mittelmeerinseln Griechenlands blieb dieses Wissen bis heute bewahrt. S. scardica
gehört zu den Gliedkräutern (lange Stengel mit mehreren Blatt-und Blütenansätzen).
Heute weiß die Botanik von über 150 bekannten Species zu berichten. In 2010
wurden erstmals verschiedene Sideritis Species systematisch durch eine
pharmakologische Prüfung anhand eines Serotonin-reuptake Modells in-vitro
verglichen [2]. Danach erwies sich unter Tee-analogen, wässrigen Extrakten die
Species Sideritis scardica am wirksamsten. Diese Daten konnten in 2012 sowohl für
einen rein wässrigen als auch einen rein methanolischen Extrakt mit S. scardica Tee
aus dem Fachhandel bestätigt werden [3].
Aufgabe der vorliegenden Arbeit war es, basierend auf einer kommerziell
verfügbaren Drogencharge aus Anbau (Lieferant Martin Bauer GmbH, Alveslohe) den
Einfluss verschiedener Extraktionsmittel auf die pharmakolog. Aktivität zu testen.
Zur Extraktion wurde die getrocknete, oberirdische Ware in ca. 1cm Teilstücke
geschnitten und mittels erschöpfender Perkolation 1:20 extrahiert. Die Ansatzgröße
bestand aus mind. 10kg Droge. Die Lösemittel waren gereinigtes Wasser, EtOH 20%
V/V, EtOH 40% V/V und EtOH 60% V/V. Die erhaltenen Eluate wurden filtriert, im
Vakuum zu Dickextrakten lösemittelfrei beigedampft, entkeimend behandelt und
final durch Zugabe von 30% Maltodextrin als Trocknungshilfsstoff per
Vakuumtrocknung zu einer homogenen, pulvrigen Extraktzubereitung überführt.
Dabei ergab sich folgende Extrakt-Charakteristik (alle 70% Nativanteil):
Innerhalb der Flavonoide waren Acteosid und Apigenin-7-glucosid typische
Leitsubstanzen in der HPLC, zu den polaren Polyphenolen gehörten u.a. die
Caffeoylchinasäuren. Auch Iridoidsubstanzen waren qualitativ nachweisbar.
Extrakte aus Griechischem Bergtee hemmen die Wiederaufnahme von Neurotransmittern
Björn Feistel1 , Kurt Appel2,
1 Finzelberg GmbH & Co. KG, Koblenzer Strasse 48-56, D - 56626 Andernach , 2Vivacell Biotechnology GmbH, Ferdinand-Porsche Str. 5, D 79211 Denzlingen
Phytokongress 2013 - Phytotherapie im Spannungsfeld zwischen Forschung und Praxis 08.-10. März 2013, Leipzig
Griechischer Bergtee Sideritis scardica
[1] Österreichisches Lebensmittelbuch, IV. Auflage, Codexkapitel Tee und teeähnliche
Erzeugnisse, BMGFJ -75219/0012-IV/B/7/2007 vom 20.07.2007
[2] Walbroel, B., Feistel, B.: Greek Mountain Tea an herbal drug for mental
enhancement. Poster P592; 58th Int Congr of the Soc. for Med Plant and Nat Prod
Res, Sept. 2010, Berlin - Germany
[3] Knörle, R.: Extracts of Sideritis scardica as triple monoamine reuptake inhibitors,
J Neural Transm 2012 Dec. 119(12):1477-82.
[4] Perovic S, Müller WE. Pharmacological profile of hypericum extract. Effect on
serotonin uptake by postsynaptic receptors. Arzneimittelforschung. 1995
Nov;45(11):1145-8.
Foto A - http://commons.wikimedia.org/wiki/File:Sideritis_scardica_IMG_4653.jpg
Foto B - E: © by Martin-Bauer-Group / Greuther Teeladen
Zusammenfassung
Literatur / Referenzen
Meßmethodik (in-vitro)
Extraktzubereitungen
Alle Testextrakte inhibieren die Aufnahme der drei Neurotransmitter dosisabhängig.
Die Wiederaufnahme-Hemmung von Noradrenalin und Dopamin ist deutlich stärker
als die von Serotonin. Die Ergebnisse bestätigen den wichtigen Einfluss des
Auszugsmittels. Mit steigender Lipophilie des Auszugsmittels (EtOH 60% V/V > EtOH
40% V/V > EtOH 20% V/V > Wasser) konnten sinkende IC50-Werte bestimmt werden.
Für Wasser als Extraktionsmittel wurden um den Faktor 3 6 höhere IC50-Werte
gemessen, was für die Extrakte eine gegenüber dem Tee erwartete
Aktivitätssteigerung verdeutlicht.
Die insgesamt sehr gute Inhibierung der Wiederaufnahme von Neurotransmittern
bestätigt erneut das ausgezeichnete Potential von Extrakten aus Sideritis scardica
und rückt eine Anwendung bei Krankheiten z.B. Depression, ADHS oder bei mentaler
Beeinträchtigung in den zukünftigen Fokus.
Die Effekte der Extrakte hinsichtlich der Hemmung der Wiederaufnahme von
Serotonin, Dopamin und Noradrenalin wurde an Synaptosomen von Ratten
untersucht. Die Durchführung erfolgte wie bei Perovic und Müller (1995)
beschrieben [4]. Die Synaptosomen wurden zusammen mit [3H]-Serotonin, [3H]-
Dopamin oder [3H]-Noradrenalin und steigenden Konzentrationen der Extrakte
inkubiert. Nach 20 min Inkubation bei 37° C wurde die Reaktion mittels Vakuum-
filtration auf GF/C-Filterplatten (PerkinElmer) gestoppt. Die Filterplatten wurden
anschliesend mit eiskaltem Puffer [4] gewaschen und getrocknet. Die auf den
Filterplatten gebundene Radioaktivitat wurde mit einem Mikrotiterplattencounter
bestimmt (Microbeta, Wallac, Finnland).
Imipramin (Serotonin), GBR 12909 (Dopamin) und Protriptylin (Noradrenalin)
wurden als Referenzsubstanzen (= Positivkontrolle) eingesetzt.
Die IC50-Werte (n=10, zweifach gemessen) wurden mittels nichtlinearer
Regressionsanalyse (algorithm sigmoidal dose-response, GraphPadPrism, San Diego,
USA) ermittelt.
A Herba S. Scardica nach
der Ernte getrocknet
C Griechischer Bergtee (S. Scar-
dica) im Greuther Teeladen
B Anbaufeld von Sideritis scardica in
Bulgarien durch Martin Bauer GmbH
Neurotransmitter-Aktivität
Anbei die graphische Darstellung für die S. scardica-Extrakte mit EtOH 20% V/V:
IC 50 Dopamin = 74µg/mL IC 50 Noradrenalin = 45µg/mL
Extraktionsmittel
Wasser
Ethanol
20% V/V
Ethanol
40% V/V
Ethanol
60% V/V
IC 50 Serotonin [µg/mL]
331
245
88
58
IC 50 Dopamin [µg/mL]
68
74
27
15
IC 50 Noradrenalin [µg/mL]
52
45
20
16
Extrakt
Extrakt
Vehicle Vehicle
Extraktionsmittel
Wasser
EtOH 40% V/V
EtOH 60% V/V
Temperatur
80°C
45°C
45°C
Extraktausbeute
19%
13%
15%
DEV nativ
5,3 : 1
7,7 : 1
6,7 : 1
Flavonoide [HPLC]
1,38%
4,03%
4,33%
Polyphenole [UV]
nach Folin-Ciocalteu-Methode
DC-Prüfung
6,31%
Bahn 1
7,49%
Bahn 3
6,98%
Bahn 4
Foto D:
Ohne Derivatiserung
UV 365 nm
Foto E:
Nach Derivatisierung
im Weißlicht
DC-Prüfung auf polare Inhaltsstoffe
Stationäre Phase: Kieselgel 60 F254
Laufmittel:
Dichlorethan - Essigsäure 99% -
Methanol - Wasser
50 : 25 : 15 : 10 (V/V/V/V)
(mit ca. 20 min. Kammersättigung)
Laufstrecke: ca. 15 cm
Derivatisierung: Anisaldehyd-
Reagenz R
Testextrakt: Löse 1g pulverisierten
Extrakt in 15 mL Methanol 75% m/m
mit Hilfe eines Ultraschallbades,
filtriere die Untersuchungslösung
über 0,45µm zu einer klaren Lösung;
20µl werden hiervon auftragen.
... Recently the effects of S. scardica extracts on the central nervous system were addressed in a number of studies. Hydroalcoholic extracts were able to inhibit the reuptake of the monoamine neurotransmitters noradrenaline, dopamine and serotonin in vitro (Feistel & Appel, 2013;Knörle, 2012). Furthermore, they showed antidepressant and psychostimulating effects, as well as a modulation of AMPA-dependent neurotransmission in rats (Dimpfel, 2013;Dimpfel et al., 2016a). ...
Preprint
Full-text available
Background. Beyond its traditional uses in the Balkan area, Sideritis scardica (known as Greek mountain tea, Lamiaceae) is currently extensively investigated for its pharmacological activity in the central nervous system. Antidepressant, psychostimulating, cognition-enhancing and neuroprotective properties have been described. In this study, we tested hydroalcoholic extracts of S. scardica for their potential to counteract amyloid-β toxicity and aggregation, which plays a crucial role in the pathogenesis of Alzheimer's disease. Methods. For this purpose, we have chosen the nematode Caenorhabditis elegans , which is used as a model organism for neurodegenerative diseases. The concentration of different polyphenols in extracts prepared from water, 20, 40, 50, and 70 % ethanol was analysed by HPLC. Additionally, polar and unpolar fractions were prepared from the 40 % ethanolic extract and phytochemically analysed. Results. Essentially, the contents of all measured constituents increased with the lipophilicity of the extraction solvents. Treatment of transgenic C. elegans strains expressing amyloid-β with the extracts resulted in a reduced number of peptide aggregates in the head region of the worms and alleviated toxicity of amyloid-β, observable through the degree of paralysed animals. The mid-polar extracts (40 and 50 % ethanol) turned out be the most active, decreasing the plaque number by 21 % and delaying the amyloid-β-induced paralysis by up to 3.5 h. The more lipophilic extract fractions exhibited higher activity than the hydrophilic ones. Discussion. Sideritis scardica extracts demonstrated pharmacological activity against characteristics of Alzheimer's disease also in C. elegans , supporting current efforts to assess its potential for the treatment of cognitive decline. The active principle as well as the mode of action needs to be investigated in more detail.
... Recently the effects of S. scardica extracts on the central nervous system were addressed in a number of studies. Hydroalcoholic extracts were able to inhibit the reuptake of the monoamine neurotransmitters noradrenaline, dopamine and serotonin in vitro (Feistel & Appel, 2013;Knörle, 2012). Furthermore, they showed antidepressant and psychostimulating effects, as well as a modulation of AMPA-dependent neurotransmission in rats (Dimpfel, 2013;Dimpfel et al., 2016a). ...
Preprint
Full-text available
Background. Beyond its traditional uses in the Balkan area, Sideritis scardica (known as Greek mountain tea, Lamiaceae) is currently extensively investigated for its pharmacological activity in the central nervous system. Antidepressant, psychostimulating, cognition-enhancing and neuroprotective properties have been described. In this study, we tested hydroalcoholic extracts of S. scardica for their potential to counteract amyloid-β toxicity and aggregation, which plays a crucial role in the pathogenesis of Alzheimer's disease. Methods. For this purpose, we have chosen the nematode Caenorhabditis elegans , which is used as a model organism for neurodegenerative diseases. The concentration of different polyphenols in extracts prepared from water, 20, 40, 50, and 70 % ethanol was analysed by HPLC. Additionally, polar and unpolar fractions were prepared from the 40 % ethanolic extract and phytochemically analysed. Results. Essentially, the contents of all measured constituents increased with the lipophilicity of the extraction solvents. Treatment of transgenic C. elegans strains expressing amyloid-β with the extracts resulted in a reduced number of peptide aggregates in the head region of the worms and alleviated toxicity of amyloid-β, observable through the degree of paralysed animals. The mid-polar extracts (40 and 50 % ethanol) turned out be the most active, decreasing the plaque number by 21 % and delaying the amyloid-β-induced paralysis by up to 3.5 h. The more lipophilic extract fractions exhibited higher activity than the hydrophilic ones. Discussion. Sideritis scardica extracts demonstrated pharmacological activity against characteristics of Alzheimer's disease also in C. elegans , supporting current efforts to assess its potential for the treatment of cognitive decline. The active principle as well as the mode of action needs to be investigated in more detail.
Thesis
Full-text available
Sideritis scardica Griseb., also known as Greek mountain tea, is a plant that belongs to the family of Lamiaceae. It is endemic to the Balkan region, where the herb is traditionally used against a broad range of afflictions, mostly as an infusion. Over the past few years, S. scardica has been scientifically investigated for the pharmacological properties it is said to have, especially focusing on the effects in the central nervous system, such as an improved cognitive performance and the reduction of β-amyloid plaques which are typical in Alzheimer's disease. Following this issue, the main goal of the present study was to examine whether extracts of Greek mountain tea counteract further pathomechanisms of this and other neurodegenerative disorders which are a rising health concern in our ageing society. For this purpose six hydroalcoholic S. scardica extracts of different lipophilicity, that were produced and phytochemically analysed by Finzelberg GmbH & Co. KG, were investigated for their neuroprotective activity in the model organism Caenorhabditis elegans. Additionally, six fractions of one of the most potent extracts, seven isolated pure compounds and extracts of some well-known medicinal plants were tested. The mid-polar extracts of S. scardica in particular, as well as the more lipophilic fractions and the phenylethanoid glycosides, were counteracting the aggregation or toxicity of β-amyloid peptides, α-synuclein, 6-hydroxydopamine, tau- and polyglutamine proteins in vivo, whereas they did not reveal any antioxidant properties in the nematodes. The spectrum of activities of S. scardica was especially comparable with that of Bacopa monnieri (Brahmi), a plant used in ayurvedic medicine. The alleviation of the neurotoxicity of the proteins and compounds make S. scardica extracts interesting for the preventive or therapeutic treatment of Alzheimer's, Parkinson's, Huntington's and other neurodegenerative diseases. The phenylethanoids could be identified as active constituents, although synergistic effects between extractives of different polarity remain probable and have to be taken into consideration. Also, a hypothetical mode of action could be postulated: the bonding of polyphenols to the peptides, directly inhibiting their aggregation to toxic oligomers or plaques and fibrils. In the present study, the activity of hydroalcoholic Sideritis scardica extracts against hallmarks of Alzheimer's disease could be affirmed and for the first time, positive effects on further neurotoxic substances could be shown, expanding the neuropharmacological profile of the Greek mountain tea. As some studies on vertebrates and humans assessing the influence on cognitive performance and proving the harmlessness have already been conducted, high-quality clinical studies investigating the preventive or therapeutic efficacy against Alzheimer's etc. should be performed.
Data
Full-text available
Hagers monograph of Sideritis scardica
Data
Full-text available
Hagers monograph of Sideritidis scardicae herba
Article
Full-text available
Herein an ElectroEncephaloGraphic Pharmacogram (EEGP) was prepared to detect possible psychopharmacological effects [4]. Animals were exposed to Extr. Sideritis aquos. sicc. within a crossover design vs. Placebo. Single dosages were administered once a week. Control experiments only contained saline. After a 45 minutes lasting pre-drug period the test compounds were administered, followed by a break of 5 minutes before restart of the recording for the next 5 hours. Frequency spectra were obtained by Fast Fourier Transformation (FFT) and results were averaged to give 60 min periods. Statistical analysis was performed against oral solvent using the Wilcoxon, Mann and Whitney U-test. Strongest effects were seen with respect to alpha2 waves representing an activation of dopaminergic neurotransmission. Delta, theta, and especially at higher dosages alpha1 waves were also attenuated, compatible with the view of activation of the cholinergic, norepinephrinergic and serotonergic transmission systems. Strongest effects were always observed in the frontal cortex followed by the hippocampus. These brain areas are heavily involved in cognitive functioning. Therefore, it can be expected, that the administration of this extract also would improve mental performance.