In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay.
ABSTRACT Women suffering from premenstrual mastodynia often respond to stimuli of prolactin (Prl) release with a hypersecretion of this hormone. Pharmacological reduction of Prl release by dopamine agonists or treatment with extracts of Agnus castus (AC) improve the clinical situation of patients with such premenstrual symptoms. Extracts of AC contain compounds which inhibit in vivo Prl release in women as well as in vitro from dispersed rat pituitary cells. It is yet unknown whether this inhibitory action of AC is only exerted on Prl release or whether release of other pituitary hormones like LH and FSH is also affected. The effects of AC on LH and FSH release were examined in vitro using rat pituitary cell cultures. To rule out that the Prl-inhibiting properties of AC are at least in part due to a cytotoxic component, pituitary cell cultures were subjected to the MTT test. To assess whether the Prl inhibitory effect of AC preparations is due to compounds acting as dopamine (DA) agonists, we used the corpus striatum membrane DA receptor binding assay. Our results demonstrate for the first time that AC extract contains an active principle that binds to the D2 receptor. Thus, it is very likely that it is this dopaminergic principle which inhibits Prl release in vitro from rat pituitary cells. Furthermore we give evidence for the specificity of action of AC on hormone release, since gonadotropin secretion remained unaffected. The findings of the present study support the therapeutical usefulness of AC extracts for treatment of premenstrual mastodynia which is associated with hypersecretion of Prl. Furthermore, the beneficial effects of AC appear to be due to the inhibition of pituitary Prl release.
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ABSTRACT: Vitex agnus-castus (VAC) has been used since ancient Greek times and has been shown clinically to be effective for the treatment of pre-menstrual syndrome. However, its mechanism of action has only been partially determined. Compounds, fractions, and extracts isolated from VAC were used in this study to thoroughly investigate possible opioidergic activity. First, an extract of VAC was found to bind and activate μ- and δ-, but not κ-opioid receptor subtypes (MOR, DOR, and KOR respectively). The extract was then resuspended in 10% methanol and partitioned sequentially with petroleum ether, CHCl(3), and EtOAc to form four fractions including a water fraction. The highest affinity for MOR was concentrated in the CHCl(3) fraction, whereas the highest affinity for DOR was found in the CHCl(3) and EtOAc fractions. The petroleum ether fraction had the highest agonist activity at MOR and DOR. Several flavonoids from VAC were found to bind to both MOR and DOR in a dose-dependent manner; however only casticin, a marker compound for genus Vitex, was found to have agonist activity selective for DOR at high concentrations. These results suggest VAC may exert its therapeutic effects through the activation of MOR, DOR, but not KOR.Biochemical pharmacology 01/2011; 81(1):170-7. · 4.25 Impact Factor
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ABSTRACT: Herbal medicine containing Vitex agnus-castus (VAC) extract is widely used by women with premenstrual syndrome (PMS) in Europe, however, in Japan, clinical evidence remains to be determined. This study attempted to investigate the efficacy and safety profiles of VAC extract in Japanese patients with PMS. A multi-center, prospective, open-label, single-arm, phase 3 study was performed in Japanese women with PMS and aged 18-44 years. The patients received Prefemin(®) (Max Zeller Söhne AG, Romanshorn, Switzerland), containing 20 mg of VAC extract, once daily for three menstrual cycles. The efficacy profile was examined based on the intensity of ten PMS symptoms-irritability, depressed mood, anger, headache, bloating, breast fullness, skin disorder, fatigue, drowsiness, and sleeplessness-recorded by patients via a visual analog scale (VAS). In addition, the responder rate was calculated based on the total VAS score defined by the sum of the VAS scores of the first six symptoms mentioned above. Furthermore, physician's global assessment (PGA) scores were recorded. Adverse events including vital signs and laboratory test values were monitored as safety evaluation. Sixty-nine patients received Prefemin(®). After the first menstrual cycle, a statistically significant decrease in total VAS score was observed (P < 0.001), and the score continued to diminish for the following two cycles. Each of the ten symptom scores decreased significantly in this manner. In addition, the responder rate increased in a time-dependent manner; the rate at the third menstrual cycle was 91.0%, and almost all of the patients were without symptoms or exhibited only mild symptoms based on PGA. Eight patients exhibited non-serious adverse events, one of which was allergic dermatitis whose causal relationship with VAC was not ruled out. VAC extract improved PMS symptoms in Japanese patients, with no substantial adverse events. This is the first study to report the effect of VAC extract in Japanese patients.Advances in Therapy 03/2014; · 2.44 Impact Factor
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ABSTRACT: BACKGROUND: Preparations of Vitex agnus castus L. (VAC) have been shown to be effective to treat irregular menstrual cycles, cyclical mastalgia and symptoms of the premenstrual syndrome (PMS). However, the dose-effect relationship for the treatment of PMS has not yet been established. This study aimed to investigate the clinical effects of three different doses of the VAC extract Ze 440 in comparison to placebo in patients suffering from PMS. METHODS: In a multicenter, double-blind, placebo-controlled, parallel-group study, 162 female patients with PMS (18-45 years) were randomized to either placebo or different doses of Ze 440 (8, 20 and 30mg) over three menstrual cycles. PMS symptoms' severity was assessed by patients using visual analog scales (VAS) for the symptoms irritability, mood alteration, anger, headache, bloating and breast fullness. RESULTS: Each of the treatments was well tolerated. Improvement in the total symptom score (TSS) in the 20mg group was significantly higher than in the placebo and 8mg treatment group. The higher dose of 30mg, on the other hand, did not significantly decrease symptom severity compared to the 20mg treatment, providing a rational for the usage of 20mg. Corresponding results were observed with the single PMS symptom scores. CONCLUSION: This study demonstrated that the VAC extract Ze 440 was effective in relieving symptoms of PMS, when applied in a dose of 20mg. Therefore, for patients suffering from PMS, 20mg Ze 440 should be the preferred daily dose.Phytomedicine: international journal of phytotherapy and phytopharmacology 09/2012; · 2.97 Impact Factor