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  • Articles: DFG German National Licenses  (4)
  • Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry  (2)
  • Valepotriates  (2)
  • binding protein  (2)
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  • Articles: DFG German National Licenses  (4)
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  • 1
    Electronic Resource
    Electronic Resource
    In vitro effects of epoxide-bearing alepotriates on mouse early hematopoietic progenitor cells and human T-lymphocytes (1982)
    Springer
    Archives of toxicology 51 (1982), S. 37-42 
    Details
    ISSN: 1432-0738
    Keywords: Valepotriates ; Epichlorohydrin ; Scopolamine ; Granulocyte/Macrophage ; Erythrocyte ; T-Lymphocyte colony assays
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die epoxidhaltigen Valepotriate Valtrat/Isovaltrat und Dihydrovaltrat, die aus den Wurzeln von Valerianaceae isoliert und als sedative Arzneimittel benutzt werden, wurden hinsichtlich ihrer Wirkung auf untransformierte hämatopoietische Zellen untersucht, nachdem ein Alkylierungspotential und Zytotoxizität auf Tumorzellen gefunden worden waren. Die Stoffe wurden in empfindlichen in vitro-Tests bezüglich ihrer Wirkung auf Vorläuferzellen für Granulo/yten/Makrophagen (GM-CFC) und Erythrozyten (E-CFC) aus dem Knochenmark von Mäusen sowie auf Kolonie-bildende PHA-stimulierte T-Lymphozyten des menschlichen peripheren Blutes geprüft. Bei Valtrat-Zugabe betrug die ID50 für GM-CFC und T-Lymphozyten ca. 3×10−6 M, bei Dihydrovaltrat ca. 2×10−5 M. Für E-CFC-Kolonien ergab sich bei beiden Substanzen eine ID50 von ca. 3×10−8 M. Die Wirkung von Valtrat zeigte sich bei niedrigerer Konzentration als die Wirkung des bekannten Alkylans Epichlorhydrin. Das zum Vergleich untersuchte nichtalkylierende Epoxid l-Scopolamin war eindeutig am wenigsten wirksam. Die Valtrat- und Dihydrovaltrat-Effekte waren nicht reversibel durch Auswaschen der Kulturen. Es kann geschlossen werden, daß die untersuchten Valepotriate wahrscheinlich stark zytotoxisch sind für die in den Tests verwendeten untransformierten hämatopoietischen Zellen.
    Notes: Abstract The epoxide-bearing valepotriates valtrate/isovaltrate and dihydrovaltrate, isolated from Valerianaceae roots and used as common sedative drugs, were investigated for their effects on untransformed hematopoietic cells after an alkylating potential and cytotoxicity to tumor cells had been found. The compounds were added to sensitive in vitro assays using granulocyte/macrophage (GM-CFC) and erythrocyte (E-CFC) colony forming cells from murine bone marrow early progenitor cells as well as colony forming PHA-stimulated T-lymphocytes from human peripheral blood. The ID50 for both GM-CFC and T-lymphocytes incubated with valtrate was found to be about 3×10−6 M, with dihydrovaltrate about 2×10−6 M. On erythrocyte colonies (E-CFC) both compounds showed an ID50 of about 3×10−8 M. Valtrate effects were exhibited at lower concentrations than effects caused by the known alkylating agent epichlorohydrin. The non-alkylating epoxide l-scopolamine taken for reference was clearly the least effective. Valtrate and dihydrovaltrate effects on GM-CFC were not reversible by washing the cultures. It is concluded that the valepotriates investigated are likely to be strongly cytotoxic to the untransformed hematopoietic cells studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279319
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    In vitro mutagenicity of valepotriates (1985)
    Springer
    Archives of toxicology 56 (1985), S. 267-271 
    Details
    ISSN: 1432-0738
    Keywords: Valepotriates ; Mutagenicity ; Salmonella typhimurium ; E. coli ; Microsome test ; Paraoxon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Valepotriates are epoxide-bearing triesters of the monoterpene alcohol 4,7-dimethylcyclopenta-(c)-pyrane isolated from the roots of several Valerianacae species. They are regarded as the main tranquilizing constituents of these drugs. Although the valepotriates valtrate/isovaltrate (VAL) and dihydrovaltrate (DH-VAL) showed a strong alkylating activity against the nucleophilic agent 4-(p-nitrobenzyl)-pyridine (NBP), they were not clearly mutagenic for the strains TA98, TA100, TA1535, and TA1537 of Salmonella typhimurium or for the strains WP2 and WP2 uvrA− of Escherichia coli in the absence of a metabolic activation system (S9-mix). However, the valepotriates were mutagenic for TA100, WP2 and WP2 uvrA− at concentrations up to about 1.0 μmole/plate when S9-mix was added to the test system. With more than 1 μmole/plate the valepotriates were toxic in the presence of a metabolic activation system for all strains tested. The mutagenicity of the valepotriates was inversely related to the protein content of the S9-mix used. The mutagenicity and toxicity of the valepotriates could be inhibited when the S9-mix was preincubated with the esterase inhibitor paraoxon (1 mM) for 5 min before the test compounds and bacteria were added. Therefore, bioactivation of the valepotriates by an enzymatic hydrolysis of their ester groups is considered. This could be proven by activating the valepotriates with purified esterase.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00295166
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Juvenile hormone binding components of locust fat body (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Archives of Insect Biochemistry and Physiology 28 (1995), S. 291-309 
    Details
    ISSN: 0739-4462
    Keywords: juvenile hormone ; methoprene ; pyriproxyfen ; fat body ; locust ; binding protein ; receptor ; Chemistry ; Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Juvenile hormone (JH) binding components from the fat body of the African migratory locust were analyzed in a search for a potential nuclear JH receptor. Biosynthetically prepared 10R[3H]JH III gave a high proportion of specific binding to isolated nuclei and extracted proteins; data obtained with the JH analogs, [3H]methoprene and [3H]pyriproxyfen, on the other hand, were obscured by abundant non-specific binding. The vast majority of the high affinity JH III binding activity present in cytosolic and nuclear extracts was due to a high molecular weight JH binding protein (JHBP) which has previously been identified in locust hemolymph. This protein has several chromatographic forms which interfered in the search for a nuclear JH receptor. When specific antiserum was used to remove JHBP from nuclear extracts, a novel JH binding activity (NBP) was detected. NBP could be separated from JHBP by precipitation with ammonium sulfate. NBP displayed a high affinity for JH III (Kd = 0.25 nM) and JH I and JH II competed strongly for JH III binding, whereas methoprene and pyriproxyfen showed apparent competition when present in 1,000-fold excess. NBP was present in nuclear extracts at approximately 25,000 sites per cell; levels were similar in male and female locusts and were not greatly affected by the presence or absence of JH. The characteristics of NPB make it a strong candidate for a nuclear JH receptor. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/arch.940280309
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Growth of the male accessory gland in adult locusts: Roles of juvenile hormone, JH esterase, and JH binding proteins (1995)
    New York, NY [u.a.] : Wiley-Blackwell
    Archives of Insect Biochemistry and Physiology 30 (1995), S. 383-400 
    Details
    ISSN: 0739-4462
    Keywords: juvenile hormone ; pyriproxyfen ; accessory gland ; locust, esterase ; binding protein ; Chemistry ; Food Science, Agricultural, Medicinal and Pharmaceutical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: The participation of juvenile hormone (JH) in the regulation of growth and protein synthesis in the accessory reproductive gland of male Locusta migratoria has been investigated. After elimination of endogenous JH with ethoxyprecocene, the accessory gland failed to grow, but growth was restored by a single application of the JH analog, pyriproxyfen. Pyriproxyfen appeared to stimulate total protein synthesis by 3 h, with a significant effect by 12 h, in contrast to 24 h observed in fat body. The dose curve for stimulation of protein synthesis 12 h after applying pyriproxyfen gave an ED50 of 0.1 μg; the dose curve for gland growth at 72 h was biphasic, with steps at about 0.01 μg and 10 μg, suggesting two phases in JH action. SDS-PAGE analysis showed several components that were stimulated by pyriproxyfen, the effect being strongest in an 11 kDa band. A 5 kDa component was enhanced in the soluble and reduced in the particulate fraction after precocene treatment. The accessory gland contained JH esterase activity at levels about 100 times those in fat body or hemolymph, and was higher in precocene treated locusts. Binding activity for [3H]10R-JH III was high in cytosolic and nuclear fractions, and was identified immunologically as due to the previously described hemolymph JH binding protein. The results indicate that the mode of action of JH in the accessory gland may differ from that in the fat body. The presence of intracellular JH binding protein suggests a direct action of JH within the gland, that may be modulated by JH esterase. © 1995 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/arch.940300407
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    Paper (German National Licenses)
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