Novel neurological and immunological targets for salicylate-based phytopharmaceuticals and for the anti-depressant imipramine.
Identifieur interne : 001406 ( Main/Corpus ); précédent : 001405; suivant : 001407Novel neurological and immunological targets for salicylate-based phytopharmaceuticals and for the anti-depressant imipramine.
Auteurs : G. Ulrich-Merzenich ; O. Kelber ; A. Koptina ; A. Freischmidt ; J. Heilmann ; J. Müller ; H. Zeitler ; M F Seidel ; M. Ludwig ; E U Heinrich ; H. WinterhoffSource :
- Phytomedicine : international journal of phytotherapy and phytopharmacology [ 1618-095X ] ; 2012.
English descriptors
- KwdEn :
- Animals (MeSH), Antidepressive Agents (pharmacology), Antidepressive Agents (therapeutic use), Antidepressive Agents, Tricyclic (pharmacology), Antidepressive Agents, Tricyclic (therapeutic use), Benzyl Alcohols (analysis), Benzyl Alcohols (pharmacology), Benzyl Alcohols (therapeutic use), Brain (drug effects), Brain (immunology), Brain (metabolism), Cytokines (blood), Depression (drug therapy), Depression (immunology), Depression (metabolism), Drug Delivery Systems (MeSH), Flavonoids (analysis), Flavonoids (pharmacology), Flavonoids (therapeutic use), Gene Expression (MeSH), Glucosides (pharmacology), Glucosides (therapeutic use), Imipramine (pharmacology), Imipramine (therapeutic use), Inflammation (drug therapy), Inflammation (genetics), Inflammation (metabolism), Male (MeSH), Microarray Analysis (MeSH), Phytotherapy (MeSH), Plant Bark (MeSH), Plant Extracts (chemistry), Plant Extracts (pharmacology), Rats (MeSH), Rats, Sprague-Dawley (MeSH), Salicylic Acid (pharmacology), Salicylic Acid (therapeutic use), Salix (chemistry), Serotonin (metabolism), Swimming (MeSH).
- MESH :
- chemical , analysis : Benzyl Alcohols, Flavonoids.
- chemical , blood : Cytokines.
- chemical , chemistry : Plant Extracts.
- chemical , metabolism : Serotonin.
- chemical , pharmacology : Antidepressive Agents, Antidepressive Agents, Tricyclic, Benzyl Alcohols, Flavonoids, Glucosides, Imipramine, Plant Extracts, Salicylic Acid.
- chemical , therapeutic use : Antidepressive Agents, Antidepressive Agents, Tricyclic, Benzyl Alcohols, Flavonoids, Glucosides, Imipramine, Salicylic Acid.
- chemistry : Salix.
- drug effects : Brain.
- drug therapy : Depression, Inflammation.
- genetics : Inflammation.
- immunology : Brain, Depression.
- metabolism : Brain, Depression, Inflammation.
- Animals, Drug Delivery Systems, Gene Expression, Male, Microarray Analysis, Phytotherapy, Plant Bark, Rats, Rats, Sprague-Dawley, Swimming.
Abstract
Inflammatory processes are increasingly recognised to contribute to neurological and neuropsychatric disorders such as depression. Thus we investigated whether a standardized willow bark preparation (WB) which contains among other constituents salicin, the forerunner of non-steroidal antiphlogistic drugs, would have an effect in a standard model of depression, the forced swimming test (FST), compared to the antidepressant imipramine. Studies were accompanied by gene expression analyses. In order to allocate potential effects to the different constituents of WB, fractions of the extract with different compositions of salicyl alcohol derivative and polyphenols were also investigated. Male Sprague Dawley rats (n=12/group) were treated for 14 days (p.o.) with the WB preparation STW 33-I (group A) and its fractions (FR) (groups FR-B to E) in concentrations of 30 mg/kg. The FRs were characterized by a high content of flavone and chalcone glycosides (FR-B), flavonoid glycosides and salicyl alcohol derivatives (FR-C), salicin and related salicyl alcohol derivatives (FR-D) and proanthocyanidines (FR-E). The tricyclic antidepressant imipramine (20 mg/kg) (F) was used as positive control. The FST was performed on day 15. The cumulative immobility time was significantly (p<0.05) reduced in group A (36%), group FR-D (44%) and by imipramine (16%) compared to untreated controls. RNA was isolated from peripheral blood. RNA samples (group A, group FR-D, and imipramine) were further analysed by rat whole genome microarray (Agilent) in comparison to untreated controls. Quantitative PCR for selected genes was performed. Genes (>2 fold, p<0.01), affected by WB and/or FR-D and imipramine, included both inflammatory (e.g. IL-3, IL-10) and neurologically relevant targets. Common genes regulated by WB, FR-D and imipramine were GRIA 2 ↓, SRP54 ↓, CYP26B ↓, DNM1L ↑ and KITLG ↓. In addition, the hippocampus of rats treated (27 d) with WB (15-60 mg/kg WB) or imipramine (15 mg/kg bw) showed a slower serotonin turnover (5-hydroxyindol acetic acid/serotonin (p<0.05)) depending on the dosage. Thus WB (30 mg/kg), its ethanolic fraction rich in salicyl alcohol derivatives (FR-D) (30 mg/kg) and imipramine, by being effective in the FST, modulated known and new targets relevant for neuro- and immunofunctions in rats. These findings contribute to our understanding of the link between inflammation and neurological functions and may also support the scope for the development of co-medications from salicylate-containing phytopharmaceuticals as multicomponent mixtures with single component synthetic drugs.
DOI: 10.1016/j.phymed.2012.05.004
PubMed: 22743246
Links to Exploration step
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<term>Antidepressive Agents (pharmacology)</term>
<term>Antidepressive Agents (therapeutic use)</term>
<term>Antidepressive Agents, Tricyclic (pharmacology)</term>
<term>Antidepressive Agents, Tricyclic (therapeutic use)</term>
<term>Benzyl Alcohols (analysis)</term>
<term>Benzyl Alcohols (pharmacology)</term>
<term>Benzyl Alcohols (therapeutic use)</term>
<term>Brain (drug effects)</term>
<term>Brain (immunology)</term>
<term>Brain (metabolism)</term>
<term>Cytokines (blood)</term>
<term>Depression (drug therapy)</term>
<term>Depression (immunology)</term>
<term>Depression (metabolism)</term>
<term>Drug Delivery Systems (MeSH)</term>
<term>Flavonoids (analysis)</term>
<term>Flavonoids (pharmacology)</term>
<term>Flavonoids (therapeutic use)</term>
<term>Gene Expression (MeSH)</term>
<term>Glucosides (pharmacology)</term>
<term>Glucosides (therapeutic use)</term>
<term>Imipramine (pharmacology)</term>
<term>Imipramine (therapeutic use)</term>
<term>Inflammation (drug therapy)</term>
<term>Inflammation (genetics)</term>
<term>Inflammation (metabolism)</term>
<term>Male (MeSH)</term>
<term>Microarray Analysis (MeSH)</term>
<term>Phytotherapy (MeSH)</term>
<term>Plant Bark (MeSH)</term>
<term>Plant Extracts (chemistry)</term>
<term>Plant Extracts (pharmacology)</term>
<term>Rats (MeSH)</term>
<term>Rats, Sprague-Dawley (MeSH)</term>
<term>Salicylic Acid (pharmacology)</term>
<term>Salicylic Acid (therapeutic use)</term>
<term>Salix (chemistry)</term>
<term>Serotonin (metabolism)</term>
<term>Swimming (MeSH)</term>
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<keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Benzyl Alcohols</term>
<term>Flavonoids</term>
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<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Cytokines</term>
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<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Plant Extracts</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Serotonin</term>
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<term>Antidepressive Agents, Tricyclic</term>
<term>Benzyl Alcohols</term>
<term>Flavonoids</term>
<term>Glucosides</term>
<term>Imipramine</term>
<term>Plant Extracts</term>
<term>Salicylic Acid</term>
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<term>Flavonoids</term>
<term>Glucosides</term>
<term>Imipramine</term>
<term>Salicylic Acid</term>
</keywords>
<keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Salix</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Depression</term>
<term>Inflammation</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Inflammation</term>
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<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Brain</term>
<term>Depression</term>
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<term>Drug Delivery Systems</term>
<term>Gene Expression</term>
<term>Male</term>
<term>Microarray Analysis</term>
<term>Phytotherapy</term>
<term>Plant Bark</term>
<term>Rats</term>
<term>Rats, Sprague-Dawley</term>
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<front><div type="abstract" xml:lang="en">Inflammatory processes are increasingly recognised to contribute to neurological and neuropsychatric disorders such as depression. Thus we investigated whether a standardized willow bark preparation (WB) which contains among other constituents salicin, the forerunner of non-steroidal antiphlogistic drugs, would have an effect in a standard model of depression, the forced swimming test (FST), compared to the antidepressant imipramine. Studies were accompanied by gene expression analyses. In order to allocate potential effects to the different constituents of WB, fractions of the extract with different compositions of salicyl alcohol derivative and polyphenols were also investigated. Male Sprague Dawley rats (n=12/group) were treated for 14 days (p.o.) with the WB preparation STW 33-I (group A) and its fractions (FR) (groups FR-B to E) in concentrations of 30 mg/kg. The FRs were characterized by a high content of flavone and chalcone glycosides (FR-B), flavonoid glycosides and salicyl alcohol derivatives (FR-C), salicin and related salicyl alcohol derivatives (FR-D) and proanthocyanidines (FR-E). The tricyclic antidepressant imipramine (20 mg/kg) (F) was used as positive control. The FST was performed on day 15. The cumulative immobility time was significantly (p<0.05) reduced in group A (36%), group FR-D (44%) and by imipramine (16%) compared to untreated controls. RNA was isolated from peripheral blood. RNA samples (group A, group FR-D, and imipramine) were further analysed by rat whole genome microarray (Agilent) in comparison to untreated controls. Quantitative PCR for selected genes was performed. Genes (>2 fold, p<0.01), affected by WB and/or FR-D and imipramine, included both inflammatory (e.g. IL-3, IL-10) and neurologically relevant targets. Common genes regulated by WB, FR-D and imipramine were GRIA 2 ↓, SRP54 ↓, CYP26B ↓, DNM1L ↑ and KITLG ↓. In addition, the hippocampus of rats treated (27 d) with WB (15-60 mg/kg WB) or imipramine (15 mg/kg bw) showed a slower serotonin turnover (5-hydroxyindol acetic acid/serotonin (p<0.05)) depending on the dosage. Thus WB (30 mg/kg), its ethanolic fraction rich in salicyl alcohol derivatives (FR-D) (30 mg/kg) and imipramine, by being effective in the FST, modulated known and new targets relevant for neuro- and immunofunctions in rats. These findings contribute to our understanding of the link between inflammation and neurological functions and may also support the scope for the development of co-medications from salicylate-containing phytopharmaceuticals as multicomponent mixtures with single component synthetic drugs.</div>
</front>
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<DateCompleted><Year>2012</Year>
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<Title>Phytomedicine : international journal of phytotherapy and phytopharmacology</Title>
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<ArticleTitle>Novel neurological and immunological targets for salicylate-based phytopharmaceuticals and for the anti-depressant imipramine.</ArticleTitle>
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<Abstract><AbstractText>Inflammatory processes are increasingly recognised to contribute to neurological and neuropsychatric disorders such as depression. Thus we investigated whether a standardized willow bark preparation (WB) which contains among other constituents salicin, the forerunner of non-steroidal antiphlogistic drugs, would have an effect in a standard model of depression, the forced swimming test (FST), compared to the antidepressant imipramine. Studies were accompanied by gene expression analyses. In order to allocate potential effects to the different constituents of WB, fractions of the extract with different compositions of salicyl alcohol derivative and polyphenols were also investigated. Male Sprague Dawley rats (n=12/group) were treated for 14 days (p.o.) with the WB preparation STW 33-I (group A) and its fractions (FR) (groups FR-B to E) in concentrations of 30 mg/kg. The FRs were characterized by a high content of flavone and chalcone glycosides (FR-B), flavonoid glycosides and salicyl alcohol derivatives (FR-C), salicin and related salicyl alcohol derivatives (FR-D) and proanthocyanidines (FR-E). The tricyclic antidepressant imipramine (20 mg/kg) (F) was used as positive control. The FST was performed on day 15. The cumulative immobility time was significantly (p<0.05) reduced in group A (36%), group FR-D (44%) and by imipramine (16%) compared to untreated controls. RNA was isolated from peripheral blood. RNA samples (group A, group FR-D, and imipramine) were further analysed by rat whole genome microarray (Agilent) in comparison to untreated controls. Quantitative PCR for selected genes was performed. Genes (>2 fold, p<0.01), affected by WB and/or FR-D and imipramine, included both inflammatory (e.g. IL-3, IL-10) and neurologically relevant targets. Common genes regulated by WB, FR-D and imipramine were GRIA 2 ↓, SRP54 ↓, CYP26B ↓, DNM1L ↑ and KITLG ↓. In addition, the hippocampus of rats treated (27 d) with WB (15-60 mg/kg WB) or imipramine (15 mg/kg bw) showed a slower serotonin turnover (5-hydroxyindol acetic acid/serotonin (p<0.05)) depending on the dosage. Thus WB (30 mg/kg), its ethanolic fraction rich in salicyl alcohol derivatives (FR-D) (30 mg/kg) and imipramine, by being effective in the FST, modulated known and new targets relevant for neuro- and immunofunctions in rats. These findings contribute to our understanding of the link between inflammation and neurological functions and may also support the scope for the development of co-medications from salicylate-containing phytopharmaceuticals as multicomponent mixtures with single component synthetic drugs.</AbstractText>
<CopyrightInformation>Copyright © 2012 Elsevier GmbH. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ulrich-Merzenich</LastName>
<ForeName>G</ForeName>
<Initials>G</Initials>
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<Language>eng</Language>
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<Month>06</Month>
<Day>27</Day>
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