Vitex Agnus-castus Extract Research Articles

Can Vitex Agnus castus Be Used for the Treatment of Mastalgia? What Is the Current Evidence?

There have been many treatments suggested for the management of mastalgia; one of these is the fruit extract of Vitex Agnus castus L. commonly known as Agnus castus, an extract of a deciduous shrub native to Mediterranean Europe and Central Asia. It is postulated that A. castus suppresses the stress-induced latent hyperprolactinemia which is a release of supra-physiological levels of prolactin in some patients in response to stressful stimuli. It is postulated that A. castus could be effective in the treatment of cyclical mastalgia by inhibiting the release of excess prolactin by blocking Dopamine-2 receptor type on pituitary. The adverse events following A. castus treatment are mild and reversible. The aim of this review is assess the efficacy of A. castus in the treatment of mastalgia. Data from randomized and non-randomized studies regarding the efficacy and safety of A. castus is reviewed in a systematic fashion. It is concluded that A. castus can be considered as an efficient alternative phytotherapeutic agent in the treatment of mastalgia.

An aqueous extract of Vitex agnus castus alters the labeling of blood constituents with technetium-99m

The development of experimental assays to study properties of herbal medicine is worthwhile. Vitex agnus castus (VAC) is utilized in popular medicine and some actions have been attributed to its extract. Blood cells (BC) and plasma proteins are labeled with technetium-99m (Tc-99m) and have been used in nuclear medicine, as in basic research. This procedure uses a reducing agent and stannous ion is utilized. There are reports that drugs can alter this labeling process. The aim of this work was to evaluate the influence of an aqueous extract of VAC on the labeling of blood constituents with Tc-99m. Blood was incubated with VAC, stannous chloride and Tc-99m, as sodium pertechnetate, and centrifuged. Samples of BC and plasma were separated, aliquots of BC and plasma were also precipitated with trichloroacetic acid to obtain soluble and insoluble fractions and the percentage of radioactivity (%ATI) was determined. The results show a statistical (p<0.05) alteration in the %ATI on blood compartments and on the insoluble fractions of plasma and BC. Probably, this extract would have chemical compounds with oxidant properties.

CNS dopamine agonistic action of the Vitex agnus castus extract Ze 440 in freely moving, chronically instrumented animals

Dopamine agonistic action is intensively under investigation because of their usefulness in movement disorder. Extracts prepared from Vitex agnus castus (VAC) showed remarkable dopamine agonistic actions believed to inhibit exaggerated prolactin release in premenstrual syndrome. In order to investigate whether orally administered VAC besides inhibition of stimulated prolactin release induces general dopamine action within the central nervous system (CNS), the pattern of field potentials were recorded from electrodes positioned in frontal cortex, hippocampus, striatum and reticular formation. All four electrodes were placed 3mm lateral within the left hemisphere (anterior coordinates are 12.2, 5.7, 9.7 and 3.7, according to the atlas of Paxinos and Watson). Animals were given 2 weeks for recovery from the surgical procedure. The electrical activity was amplified and transmitted wireless from the freely moving rats. Signals were collected in sweeps of 4s duration and submitted to Fast Fourier Transformation. The resulting power spectra were divided into 6 frequency ranges (delta, theta, alpha 1, alpha 2, beta 1 and beta 2). Spectra were averaged in steps of 3 minutes each and displayed on-line. In an off-line procedure spectra were averaged to provide 60 minutes periods for data presentation and further statistical analysis. Changes of electrical power (µV2/ω) are expressed as % of the 45min absolute pre-dose electrical power values within each frequency band. Mobility was measured by a video tracking system (GJB Datentechnik, D). Oral administration of saline did not show any changes in the EEG power spectrum. Administration of 10, 25 and 50mg of the special VAC extract Ze 440/kg body weight (BW) dose related changed the alpha 2 frequency band as well as delta and theta frequencies predominantly in frontal cortex and striatum. The largest effect was caused by 25mg Ze 440/kg BW. Administration of a potent dopamine D2 receptor blocker (L 741,626; 2mg/kg BW) prior to oral administration of 25mg Ze 440/kg BW abolished the EEG responses in the frontal cortex but not those in the striatum. Oral administration of 10, 25 or 50mg Ze 440/kg BW prevented the normal decrease of mobility with time, whilst the combination of 25mg Ze 440/kg BW with the dopamine D2 antagonist led to higher mobility.

Vitex agnus castus: Successful treatment of moderate to severe premenstrual syndrome

Objectives To assess efficacy and tolerability of a special extract of Vitex agnus castus (VAC, BNO 1095) in the treatment of women suffering from premenstrual syndrome (PMS) with moderate to severe complaints. Methods Prospective, open, non-comparative, monocentre study. After a run-in phase lasting three cycles, eligible patients were treated for up to three cycles with VAC extract. Efficacy was assessed using a PMS-Diary (primarily) and the PMTS score. Results One hundred and twenty-one patients were enrolled, 118 provided efficacy data (full analysis set), and 109 completed the treatment phase. The severity of the PMS symptoms consistently decreased during treatment, on average from 22.8 score points during the baseline cycle to 10.2 during the third cycle. The mean decrease was 12.6 score points (95% CI: 10.9–14.4, p < 0.0001, Student's t-test). Response to treatment was found in 67.8% of the women during the third treatment cycle (95% CI: 58.6–77.0). Results for the PMTS were similar with a decrease on average from 22.5 to 11.0 score points, i.e. mean change −11.4 (95% CI: 10.1–12.8, p < 0.0001). Conclusion Vitex agnus castus extract BNO 1095 is effective and well tolerated in the treatment of moderate to severe PMS.

In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus

Introduction Extracts 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. Methods Estrogen receptor (ER) and Dopamine D 2-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. Results The 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. Conclusion Using 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.

Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones.

Recent cell culture experiments indicated that extracts of Vitex agnus-castus (VAC) may contain yet unidentified phytoestrogens. Estrogenic actions are mediated via estrogen receptors (ER). To investigate whether VAC compounds bind to the currently known isoforms ERalpha or ERss, ligand binding assays (LBA) were performed. Subtype specific ER-LBA revealed a binding of VAC to ERss only. To isolate the ERss-selective compounds, the extract was fractionated by bio-guidance. The flavonoid apigenin was isolated and identified as the most active ERss-selective phytoestrogen in VAC. Other isolated compounds were vitexin and penduletin. These data demonstrate that the phytoestrogens in VAC are ERss-selective.

Pharmacological activities of Vitex agnus-castus extracts in vitro.

The pharmacological effects of ethanolic Vitex agnus-castus fruit-extracts (especially Ze 440) and various extract fractions of different polarities were evaluated both by radioligand binding studies and by superfusion experiments. A relative potent binding inhibition was observed for dopamine D2 and opioid (micro and kappa subtype) receptors with IC50 values of the native extract between 20 and 70 mg/mL. Binding, neither to the histamine H1, benzodiazepine and OFQ receptor, nor to the binding-site of the serotonin (5-HT) transporter, was significantly inhibited. The lipophilic fractions contained the diterpenes rotun-difuran and 6beta,7beta-diacetoxy-13-hydroxy-labda-8,14-dien . They exhibited inhibitory actions on dopamine D2 receptor binding. While binding inhibition to mu and kappa opioid receptors was most pronounced in lipophilic fractions, binding to delta opioid receptors was inhibited mainly by a aqueous fraction. Standardised Ze 440 extracts of different batches were of constant pharmacological quality according to their potential to inhibit the binding to D2 receptors. In superfusion experiments, the aqueous fraction of a methanolic extract inhibited the release of acetylcholine in a concentration-dependent manner. In addition, the potent D2 receptor antagonist spiperone antagonised the effect of the extract suggesting a dopaminergic action mediated by D2 receptor activation. Our results indicate a dopaminergic effect of Vitex agnus-castus extracts and suggest additional pharmacological actions via opioid receptors.

Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study

In a placebo-controlled, randomized, double-blind study the efficacy of a Vitex agnus castus extract-containing solution* (VACS) was investigated in patients suffering from cyclical mastalgia. Patients had mastalgia on at least 5 days in the pre-treatment cycle. During this cycle and during treatment (3 cycles; 2 × 30 drops/day), the intensity of mastalgia was recorded once per cycle using a visual analogue scale (VAS). After one/two treatment cycles, the mean decrease in pain intensity (mm, VAS) was 21.4 mm /33.7 mm in women taking VACS ( n= 48) and 10.6 mm/20.3 mm with placebo ( n=49). The differences of the VAS-values for VACS were significantly greater than those with placebo ( p= 0.018; p= 0.006). After three cycles, the mean VAS-score reduction for women taking VACS was 34.3 mm, a reduction of ‘borderline significance’ ( p= 0.064) on statistical testing compared with placebo (25.7 mm). There was no difference in the frequency of adverse events between both groups (VACS: n = 5; placebo: n= 4). VACS appears effective and was well tolerated and further evaluation of this agent in the treatment of cyclical mastalgia is warranted.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.