کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1919062 1047990 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus
چکیده انگلیسی

IntroductionExtracts of Vitex agnus-castus (VAC) are used for the treatment of premenstrual symptoms. The mechanism of action was proposed to be dopaminergic and estrogenic in nature. To isolate these endocrinologically active substances, receptor ligand binding assays and cell cultures were used as in vitro systems to monitor the bioactivity-guided chromatographic separation.MethodsEstrogen receptor (ER) and Dopamine D2-receptor ligand binding assays were performed with human recombinant receptor protein. Both known ERs (ERα and ERβ) were used. Cultures of anterior pituitary cells were prepared from 3 months old female rats. The concentrations of prolactin (PRL) and of cAMP in the supernatants were measured by radio immunoassay (RIA). Starting material for the isolation of single constituents was the aqueous ethanol 70% (v/v) VAC extract BNO 1095. The fractionations were performed with high speed counter current or Sephadex-LH-20 chromatography. Structure elucidation was conducted with GC–MS, LC–MS, 1H NMR and 13C NMR.ResultsThe bio-guided fractionation of BNO 1095 resulted in the isolation of dopaminergic bicyclic diterpenes. The fraction with the highest dopaminergic activity was a mixture of diterpenes of the clerodane type, designated as “BNO-diterpenes”. These newly isolated diterpenes inhibited cAMP formation and PRL-release in rat pituitary cell cultures. The estrogenic compounds in BNO 1095 were identified as the flavonoids penduletin and apigenin. Both substances are specific ligands for the ERβ.ConclusionUsing the strategy of bioactivity-guided fractionation we were able to isolate new dopaminergic diterpenes with a high specific activity which contribute significantly to the PRL-lowering activity of VAC. The therapeutical potential of the ERβ specific ligands penduletin and apigenin needs further investigation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Maturitas - Volume 55, Supplement 1, 1 November 2006, Pages S26–S36
نویسندگان
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