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2.
Article in English | MEDLINE | ID: mdl-37874338

ABSTRACT

Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic- and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice 24 h post-treatment. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than anxiolytic effects.

3.
Res Sq ; 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37461593

ABSTRACT

Serotonergic psychedelics such as psilocybin, lysergic acid diethylamide, and DOI exert a hallucinatory effect through serotonin 5-HT 2A receptor (5-HT2A) activation. Recent studies have revealed that serotonergic psychedelics have therapeutic potential for neuropsychiatric disorders, including major depressive and anxiety-related disorders. However, the involvement of 5-HT2A in mediating the therapeutic effects of these drugs remains unclear. In this study, we ethopharmacologically analyzed the role of 5-HT2A in the occurrence of anxiolytic-and antidepressant-like effects of serotonergic psychedelics such as psilocin, an active metabolite of psilocybin, DOI, and TCB-2 in mice. Mice with acute intraperitoneal psychedelic treatment exhibited significantly shorter immobility times in the forced swimming test (FST) and tail-suspension test (TST) than vehicle-treated control mice 24 h post-treatment. These effects were eliminated by pretreatment with volinanserin, a 5-HT2A antagonist. Surprisingly, the decreasing immobility time in the FST in response to acute psilocin treatment was sustained for at least three weeks. In the novelty-suppressed feeding test (NSFT), the latency to feed, an indicator of anxiety-like behavior, was decreased by acute administration of psilocin; however, pretreatment with volinanserin did not diminish this effect. In contrast, DOI and TCB-2 did not affect the NSFT performance in mice. Furthermore, psilocin, DOI, and TCB-2 treatment did not affect the spontaneous locomotor activity or head-twitch response, a hallucination-like behavior in rodents. These results suggest that 5-HT2A contributes to the antidepressant effects of serotonergic psychedelics rather than an anxiolytic effects.

4.
J Cell Physiol ; 233(2): 1700-1711, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28681912

ABSTRACT

Cell therapy using endothelial progenitor cells (EPCs) is a promising strategy for the treatment of ischemic diseases. Two types of EPCs have been identified: early EPCs and late EPCs. Late EPCs are able to form tube structure by themselves, and have a high proliferative ability. The functional marker(s) of late EPCs, which relate to their therapeutic potential, have not been fully elucidated. Here we compared the gene expression profiles of several human cord blood derived late EPC lines which exhibit different tube formation activity, and we observed that the expression of occludin (OCLN) in these lines correlated with the tube formation ability, suggesting that OCLN is a candidate functional marker of late EPCs. When OCLN was knocked down by transfecting siRNA, the tube formation on Matrigel, the S phase + G2 /M phase in the cell cycle, and the spheroid-based sprouting of late EPCs were markedly reduced, suggesting the critical role of OCLN in tube formation, sprouting, and proliferation. These results indicated that OCLN plays a novel role in neovascularization and angiogenesis.


Subject(s)
Endothelial Progenitor Cells/metabolism , Neovascularization, Physiologic , Occludin/metabolism , Cell Line , Cell Proliferation , Fetal Blood/cytology , G2 Phase Cell Cycle Checkpoints , Humans , Neovascularization, Physiologic/genetics , Occludin/genetics , RNA Interference , S Phase Cell Cycle Checkpoints , Signal Transduction , Transcriptome , Transfection
5.
J Cell Physiol ; 230(11): 2763-75, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25820539

ABSTRACT

Since the introduction of angiogenic cell therapy using early endothelial progenitor cells (EPCs), myeloid angiogenic cells (MACs) have been expected to be useful in treating ischemic diseases. In order to elucidate the angiogenic properties of MACs/EPCs, we clarified the characteristics of MACs as compared to M2 macrophages (Mϕs). Comparison of the gene expression profiles of MACs and late EPCs revealed that MACs expressed greater amounts of metalloproteinase (MMP)-9. It should be noted that the profile of MMP-2/9 expression on the cell surface of MACs was similar to that of M2 Mϕs, and that cell surface MMP-2/9 might be an active form based on molecular size. In addition, the invasion of MACs was prohibited not only by MMP-2/9 inhibitor, but also by the hyaluronidase treatment that caused the down-regulation of MMP-9 on the cell surface of MACs and inhibited their invasion activity. These results indicate that cell surface MMP-2/9 plays an important role in the high invasion ability of MACs. The conditioned medium of both MACs and M2 Mϕs stimulated tube formation of endothelial cells in vitro. MACs caused an increase in vessel formation in in vivo models through the production of IL-8. We propose that the role of MACs with cell surfaces expressing MMP-2/9 is rapidly invading ischemic tissue.


Subject(s)
Endothelial Progenitor Cells/metabolism , Matrix Metalloproteinase 9/biosynthesis , Myeloid Cells/metabolism , Neovascularization, Physiologic , Culture Media, Conditioned , Endothelial Progenitor Cells/cytology , Humans , Interleukin-8/biosynthesis , Macrophages/cytology , Macrophages/metabolism , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase Inhibitors/administration & dosage , Myeloid Cells/cytology , Myocardial Ischemia/pathology , Myocardial Ischemia/therapy , Neovascularization, Pathologic/metabolism , Vascular Endothelial Growth Factor A/metabolism
6.
DNA Seq ; 14(2): 135-9, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12825355

ABSTRACT

The Acph gene of Drosophila virilis was isolated from a genomic library and sequenced. The gene was organized into 6 exons interrupted by 5 introns. 5' and 3' RACE identified 3 transcripts ascribed to alternative splicing. One of them coded for 435 amino acid residues; and the others, for 403 amino acids. The shorter ones lacked 34 residues at the C-terminus end encoded by exon 6, which has been implicated in anchoring the protein to the lysosomal membrane.


Subject(s)
Acid Phosphatase/biosynthesis , Acid Phosphatase/genetics , Alternative Splicing , Drosophila/genetics , Amino Acid Sequence , Animals , Base Sequence , Cell Membrane/metabolism , Cloning, Molecular , Drosophila/metabolism , Exons , Introns , Lysosomes/metabolism , Models, Genetic , Molecular Sequence Data , Protein Structure, Tertiary , RNA, Messenger/metabolism , Sequence Analysis, DNA , Sequence Homology, Amino Acid
7.
Biol Pharm Bull ; 26(4): 532-9, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12673038

ABSTRACT

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the biological action of many aromatic environmental pollutants. In this study, we investigated the activation of the AhR by some vegetable constituents using the AhR-based bioassay for dioxins, i.e., the chemical activated luciferase gene expression (CALUX) assay. Ninety-five vegetable constituents, including flavonoids, tannins, saponins, and terpenes, were tested in vitro. Among them, isoflavones such as daidzein, resveratrol having a stilbene structure, and some flavonoids such as naringenin, hesperetin, and baicalein showed AhR activation.


Subject(s)
Gene Expression Regulation/drug effects , Genes, Reporter/physiology , Isoflavones/pharmacology , Receptors, Aryl Hydrocarbon/metabolism , Vegetables , Animals , Cell Line, Tumor , Drug Evaluation, Preclinical/methods , Gene Expression Regulation/physiology , Isoflavones/chemistry , Isoflavones/isolation & purification , Luciferases/biosynthesis , Luciferases/genetics , Mice , Receptors, Aryl Hydrocarbon/agonists , Receptors, Aryl Hydrocarbon/genetics
8.
Biol Pharm Bull ; 25(2): 272-4, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11853182

ABSTRACT

A preliminary screening for the inhibitory effects on the activation of the aryl hydrocarbon receptor (AhR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by applying AhR-based bioassays for dioxins, the Ah-Immunoassay and CALUX assay, was attempted. Thirty-nine food extracts including vegetables, fruits, herbs, and teas were initially screened in vitro. We first examined the application of both bioassay methods using green tea extracts and (-)-epigallocatechin gallate, reported antagonists of the AhR, since the results could reveal an inhibitory effect versus the control in both assays. Food extracts were then tested. Among the herbs, extracts of sage, among the vegetables, green leafy ones such as spinach, and among the fruit, citrus showed inhibitory effects on AhR activation by TCDD, although some tested samples did not show parallel behavior in both assays. Sage had a remarkable inhibitory effect (79% in the CALUX assay and 83% in the Ah-Immunoassay compared with control) and its effects were dose dependent. The results suggest that these assays might be applicable to the preliminary screening of antagonist activity against the AhR. Moreover, based on these results, the potential benefit of factors that function as dietary ligands of the AhR and are present in several foodstuffs is indicated.


Subject(s)
Fruit , Plant Extracts/pharmacology , Polychlorinated Dibenzodioxins/antagonists & inhibitors , Receptors, Aryl Hydrocarbon/drug effects , Tea , Vegetables , Animals , Mice , Polychlorinated Dibenzodioxins/toxicity , Tumor Cells, Cultured
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