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CHASTEBERRY (VİTEX AGNUS CASTUS) AND PROLACTİNE

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  • Malatya Turgut Özal University

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zet Vitex agnus castus eski çağlardan beri kadınlar için ilaç olarak kullanılagelmiştir. Öncelikli olarak kadın hormonlarının üretimini düzenleyen bileşiklerin varlığı araştırılmalıdır. Vitex agnus castus prolaktin salınımını düzenler. Bu özellik infertilite tedavisinde yüksek düzey-lerinin prolaktin seviyesinin azaltılmasına yaramaktadır. Abstract Vitex agnus castus has been used since ancient times as a female remedy. Preliminary investigations do in-deed show the presence of compounds which are able to adjust the production of female hormones. Vitex agnus castus may also regulate prolactin secretion. The ability to decrease excessive prolactin levels may benefit infer-tile women.
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The Journal of Gynecology - Obstetrics and Neonatology 9 (34):1421- 1424 2012 1421
CHASTEBERRY (VİTEX AGNUS CASTUS) AND
PROLACTİNE
Başar ALTINTERİM
Altınterim Bitkisel Ürünler, Elazığ-Türkiye.
Geliş Tarihi:18.03.2012 Kabul Tarihi: 19.04.2012
Özet
Vitex agnus castus eski çağlardan beri kadınlar için
ilaç olarak kullanılagelmiştir. Öncelikli olarak kadın
hormonlarının üretimini düzenleyen bileşiklerin varlığı
araştırılmalıdır. Vitex agnus castus prolaktin salınımını
düzenler. Bu özellik infertilite tedavisinde yüksek düzey-
lerinin prolaktin seviyesinin azaltılmasına yaramaktadır.
Anahtar Kelimeler: Hayıt Meyvesi, Vitex agnus cas-
tus, Prolaktin.
Abstract
Vitex agnus castus has been used since ancient times
as a female remedy. Preliminary investigations do in-
deed show the presence of compounds which are able to
adjust the production of female hormones. Vitex agnus
castus may also regulate prolactin secretion. The ability
to decrease excessive prolactin levels may benet infer-
tile women.
Keywords:Chasteberry, Vitex agnus castus, Prolactine.
Introduction
Vitex agnus castus, also known as chastetree berry,
chasteberry, monk's pepper, or simply vitex, is a fertility-
promoting herb that is useful in treating hormonal imbal-
ances. Vitex does indeed exert a normalizing effect on the
monthly cycle, as well as balance the hormones involved
in ovulation and menstrual regularity. Better yet, vitex
(FigureI) (1) also appears to increase the odds of preg-
nancy.
The fruits of Vitex agnus castus (the chaste tree)
contain a mixture of iridoids and avonoids, and some
compounds similar in structure to the sex hormones have
been isolated from the leaves and owers. The effects of
agnus castus have been described as similar to those of the
corpus luteum.
Studies have shown that extracts of Agnus cas-
tus can stimulate the release of Lutenizing Hormone (LH)
and inhibit the release of Follicle Stimulating Hormone
(FSH). This suggests that the volatile oil has a progester-
one-like effect. Its benets stem from its actions upon the
pituitary gland specically on the production of luteiniz-
ing hormone. This increases progesterone production and
helps regulate a woman's cycle.
ALTINTERİM
HAYIT MEYVESİ (VİTEX AGNUS CASTUS) VE PROLAKTİN
Figure I.: Vitex agnus castus (httpI).
Extracts of the fruits of chaste tree Vitex agnus castus are
widely used to treat premenstrual symptoms. Double-
blind placebo-controlled studies indicate that one of the
most common premenstrual symptoms, i.e. premenstrual
mastodynia (mastalgia) is benecially inuenced by an
chasteberry extract (2).
Chasteberry isolates contain avonoids, essential
oils, diterpenes, and glycosides. The avonoids (casticin,
quer-cetagetin, isovitexin (Figure I)) have been shown in
vitro to affect estrogen receptors. The mechanism of ac-
tion is not exactly understood but it is assumed that it has
dopaminergic effects resulting in changes of prolactin se-
cretion.
Vitex’ precise mechanism of action and its active
constituents have not been established. Some constituents
may have anti-inammatory, sedative, and analgesic prop-
erties. Vitex also has dopaminergic properties, although it
remains unclear which active compound is responsible.
The mechanism of action
The mechanism of action may also be related to modula-
tion of stress induced prolactin secretion via dopamine,
without directly affecting luteinising hormone or follicle
stimulating hormone (FSH).
Vitex both stimulates and regulates the key re-
productive hormones involved in ovulation and assists in
restoring balance and menstrual regularity (Figure II) (3).
Vitex agnus castus works by acting on the pitui-
tary gland and the hypothalamus, which are responsible
for releasing hormones or triggering hormone responses
throughout the reproductive system. In vitro studies de-
scribe dopaminergic effects of vitex via a dose-dependent
binding of dopamine-2 receptors, yielding potent inhibi-
tion of prolactin in cultured pituitary cells. The avonoid
apigenin can be isolated from vitex and has selective
binding afnity for the beta-estrogen receptor subtype.
Functional disorders of the menstrual cycle are typically
interpreted as signs of hormonal imbalance, with estrogen
dominance and progesterone deciency during the luteal
phase usually implicated, in addition to hyperprolacten-
emia. Chasteberry contains a variety of active compounds
that affect different aspects of the reproductive system
and create a balancing, or normalizing, effect. Some of
these active compounds include essential oils, iridoid gly-
cosides (agnuside and aucubin), and avonoids (casticin
and iso-orientin) (4).
The search for the chemical identity of the
dopaminergic compounds resulted in isolation of a
number of diterpenes of which some clerodadienols were
most important for the prolactin-suppressive effects (5).
They were almost identical in their prolactin-suppressive
properties than dopamine itself. Hence, it is concluded
that dopaminergic compounds present in Vitex agnus
castus are clinically the important compounds which im-
prove premenstrual mastodynia and possibly also other
symptoms of the premenstrual syndrome Both extracts
from Vitex agnus castus as well as synthetic dopamine
agonists (Lisuride) signicantly inhibit basal as well as
TRH-stimulated prolactin secretion of rat pituitary cells
in vitro and as a consequence inhibition of prolactin se-
cretion could be blocked by adding a dopamine receptor
blocker. Therefore because of its dopaminergic effect Ag-
nus castus could be considered as an efcient alternative
phytotherapeutic drug in the treatment of slight hyperpro-
lactinaemia (6,7).
Figure II: Vitexin
Figure III: Menstrual cycle (http 2).
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CHASTEBERRY (VİTEX AGNUS CASTUS) AND PROLACTİNE
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The Journal of Gynecology - Obstetrics and Neonatology 9 (34):1421- 1424 2012
The search for the chemical identity of the
dopaminergic compounds resulted in isolation of a number
of diterpenes of which some clerodadienols were most im-
portant for the prolactin suppressive effects. They were
almost identical in their prolactin suppressive properties
than dopamine itself. Hence, it is concluded that dopamin-
ergic compounds present in Vitex agnus castus are clini-
cally the important compounds which improve premen-
strual mastodynia and possibly also other symptoms of the
premenstrual syndrome (8,9).
In a pilot study, 56 women with mastodynia who
took a product containing chasteberry for three menstrual
cycles had signicantly reduced serum prolactin levels
compared to those taking placebo (10).
Conclusion
Clinical studies in patients with premenstrual syn-
drome, luteal insufciency, and mastopathy show a simul-
taneous decrease in the clinical syndrome score and prol-
actin levels (8).
A decrease of prolactin will inuence levels of
Follicle-stimulating hormone (FSH) and estrogen in wom-
en; and testosterone in men. Dopaminergic compounds
(diterpenes with prolactin-suppressive effects that were
almost identical in their prolactin-suppressive properties
than dopamine itself) present in Vitex agnus castus seem
likely to be the clinically important compounds which im-
prove premenstrual mastodynia and possibly also psychic
and somatic symptoms of PMS. Vitex did not modulate
follicle stimu¬lating hormone (FSH) or luteinizing hor-
mone (LH) production in rat pituitary cells (11).
Initial human studies reported inhibition of FSH
and stimulation of LH secretion and presumed the hor-
mone modulation of FSH and LH affected the downstream
hormones progesterone and estrogen (12).
Vitex agnus castus fruit extract has an anti-andro-
genic effect and probably acts through the Hypothalamic-
Pituitary- Gonadal (HPG) axis (13).
Linoleic acid also stimulated mRNA ERβ expres-
sion in T47D:A18 cells, PR expression in Ishikawa cells,
but not AP activity in Ishikawa cells. These data suggest
that linoleic acid from the fruits of Vitex agnus-castus can
bind to estrogen receptors and induce certain estrogen in-
ducible genes (14).
In vitro studies provide evidence of prolactin inhibition
with direct binding to dopamine receptors. Extracts were
also demonstrated to displace ligands in human opioid-
receptor binding (15).
Clinical reviews are available for the efcacy of
vitex in hyperprolactinaemia, but so far no systematic re-
view has been published on adverse events or drug inter-
actions associated with Vitex agnus-castus. Therefore, this
review was conducted to evaluate all the available human
safety data of vitex monopreparations. Its dominant phar-
macological effect on the body is inhibition of prolactin
secretion. V. agnuscastus is available in a variety of dosage
forms. Because of its dopaminergic effect Agnus castus
could be considered as an efcient alternative phytothera-
peutic drug in the treatment of slight hyperprolactinaemia.
There are no clinical studies assessing the safety
of vitex in children and pregnant women. Vitex is gener-
ally not recommended in pregnancy due to its unknown
effects on the pituitary.
It is concluded that dopaminergic compounds
present in Vitex agnus castus are clinically the important
compounds which improve premenstrual mastodynia and
possibly also other symptoms of the premenstrual syn-
drome.
The inuence of vitex extract is dependent on the
dosage and the initial level of the prolactin concentration.
The result is a shift in the ratio of estrogen to pro-
gesterone, in favor of progesterone. The ability of chaste
tree berry to raise progesterone levels in the body is an
indirect effect, so the herb itself is not a hormone.
References
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health/suffering-from-irregular-menstrual-cycle-nd-the-right-cause-
to-regulate-your-menstrual-cycle/
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The Journal of Gynecology - Obstetrics and Neonatology 9 (34):1421- 1424 2012 1423
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Bolton, J. L., Farnsworth, N. R. Isolation of linoleic acid as an estrogenic
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Sorumlu Yazar : Dr. Başar ALTINTERİM
Altınterim Bitkisel Ürünler, Elazığ-TÜRKİYE
Tel:0 (424) 233 42 89
web: http://www.altinterim.com
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The Journal of Gynecology - Obstetrics and Neonatology 9 (34):1421- 1424 2012
... The major active constituents of VAC are iridoid glycosides, flavonoids, alkaloids, and essential oils[4]. Its dominant pharmacological effect on the body is inhibition of prolactin secretion[4][5][6]. VAC plant parts are available in a variety of dosage forms and its use is gaining popularity in the United States. ...
Article
Full-text available
Vitex agnus-castus L (VAC) is an important medicinal plant. Seeds are used as a popular treatment for the management of female reproductive system disorders. Other uses include the treatment of hangovers, flatulence, fevers, benign prostatic hyperplasia, nervousness, dementia, rheumatic conditions, cold, dyspepsia, spleen disorders, constipation and promoting urination. VAC today is an important herb of commerce cultivated around the world. VAC seeds were collected from different geographical location—USA, EU and India. Phytochemical variations among these VAC seeds were studied using High Performance Thin Layer Chromatography (HPTLC) and High Performance Liquid Chromatography (HPLC)/fingerprinting techniques. HPTLC fingerprinting of VAC seeds were studied using agnuside and casticin as marker compound. Casticin and agnuside were quantified in all the six VAC seed samples by HPLC. Significant phytochemical variations were found among all the VAC seed samples.
Article
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Usually, the side effects of synthetic drugs appear after a long time of their usage. For that reason, these years, diseases treatment by herbal drugs is very interested. In this study, regarding to the mentioned purposes, we evaluate the effects of Vitex agnus castus L. (Vit.) fruit extract on the activity of Pituitary-Gonadal axis in Balb/C male mice. LD50 of the extract was obtained 1650 mg/kg. Regarding to the LD50 of the extract, the following doses (65, 165, 265, 365, 465 mg/kg) were injected intraperitoneally for 30 days in 5 groups of animals. After the last injection, we collected the blood samples and measured FSH, LH and testosterone by Radio Immuno Assay (RIA) technique. Vitex extract decreased the FSH, LH and testosterone levels comparing to the control and sham groups. The optimum dose was obtained 365 mg/kg. These results suggest that Vit. fruit extract has an anti-androgenic effect and probably acts through the Hypothalamic-Pituitary-Gonadal (HPG) axis. Introduction Vit. is a member of the Verbenacea family, native to the Mediterranean and central Asia (Jonina, 1999). It is a shrub with finger-shaped leaves and slender violet flowers. The fruit has a spicy pepper like aroma and taste. The dried ripe fruits are used medicinally. Vit. has a long history of use, first mentioned in the writings of Hippocrates in the 4th century BC. (Burch, 1999).
Article
The medicinal use of extracts from Vitex agnus-castus has a long tradition. The use in "disturbances of the female genital system" was first reported more than two thousand years ago. Nowadays ethanolic extracts from the fruit are used for the treatment of mastopathy, premenstrual syndrome and luteal insufficiency - complaints caused by a mild or a latent hyperprolactinemia. The mode of action of Vitex agnus-castus extracts was studied in vitro using primary cultures from rat pituitaries as a test system. A dose dependent reduction of prolactin secretion was observed. The effect could be blocked by the dopamine-receptor antagonist, haloperidol, confirming a dopamine agonistic activity of the drug. The prolactin lowering effect of Vitex agnus-castus was also found in in vivo experiments in rats. Clinical studies in patients with premenstrual syndrome, luteal insufficiency, and mastopathy show a simultaneous decrease in the clinical syndrome score and prolactin levels.
Article
There is a long tradition for the use of different preparations of drugs of Vitex agnus castus in complementary medicine in Europe. The indications in disorders of the female sexual cycle have been confirmed by experimental and clinical results. The activity of hitherto unidentified constituents of the ethanol seed extract could be localized within the pituitary–gonadal axis. Research in pituitary cell assays further elucidated a dopaminergic inhibition of prolactin synthesis and/or release. The effective administration of ethanol seed extracts against mastodynia and symptoms related to female cycle disorders with concomitant hyperprolactinaemia has been documented and awaits further establishment. © 1998 John Wiley & Sons, Ltd.
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From the fruits of Vitex agnus-castus L. one new diterpene, 6β,7β-diacetoxy-13-hydroxy-labda-8,14-diene, as well as two previously described diterpenes (rotundifuran and vitexilactone) were isolated. All obtained diterpenoids belong to the labdane typ. The structures determinations were mainly based on 1D and 2D NMR spectra and MS data interpretation. 6β,7β-diacetoxy-13-hydroxy-labda-8,14-diene and rotundifuran showed an affinity to the dopamine-D2-receptor.
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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.
Article
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.
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Extracts of the fruits of chaste tree (Vitex agnus castus = AC) are widely used to treat premenstrual symptoms. Double-blind placebo-controlled studies indicate that one of the most common premenstrual symptoms, i.e. premenstrual mastodynia (mastalgia) is beneficially influenced by an AC extract. In addition, numerous less rigidly controlled studies indicate that AC extracts have also beneficial effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia is most likely due to a latent hyperprolactinemia, i.e. patients release more than physiologic amounts of prolactin in response to stressful situations and during deep sleep phases which appear to stimulate the mammary gland. Premenstrually this unphysiological prolactin release is so high that the serum prolactin levels often approach heights which are misinterpreted as prolactinomas. Since AC extracts were shown to have beneficial effects on premenstrual mastodynia serum prolactin levels in such patients were also studied in one double-blind, placebo-controlled clinical study. Serum prolactin levels were indeed reduced in the patients treated with the extract. The search for the prolactin-suppressive principle(s) yielded a number of compounds with dopaminergic properties: they bound to recombinant DA2-receptor protein and suppressed prolactin release from cultivated lactotrophs as well as in animal experiments. The search for the chemical identity of the dopaminergic compounds resulted in isolation of a number of diterpenes of which some clerodadienols were most important for the prolactin-suppressive effects. They were almost identical in their prolactin-suppressive properties than dopamine itself. Hence, it is concluded that dopaminergic compounds present in Vitex agnus castus are clinically the important compounds which improve premenstrual mastodynia and possibly also other symptoms of the premenstrual syndrome.
Article
A methanol extract of chaste-tree berry (Vitex agnus-castus L.) was tested for its ability to displace radiolabeled estradiol from the binding site of estrogen receptors alpha (ERalpha) and beta (ERbeta). The extract at 46 +/- 3 microg/ml displaced 50% of estradiol from ERalpha and 64 +/- 4 microg/ml from ERbeta. Treatment of the ER+ hormone-dependent T47D:A18 breast cancer cell line with the extract induced up-regulation of ERbeta mRNA. Progesterone receptor (PR) mRNA was upregulated in the Ishikawa endometrial cancer cell line. However, chaste-tree berry extract did not induce estrogen-dependent alkaline phosphatase (AP) activity in Ishikawa cells. Bioassay-guided isolation, utilizing ER binding as a monitor, resulted in the isolation of linoleic acid as one possible estrogenic component of the extract. The use of pulsed ultrafiltration liquid chromatography-mass spectrometry, which is an affinity-based screening technique, also identified linoleic acid as an ER ligand based on its selective affinity, molecular weight, and retention time. Linoleic acid also stimulated mRNA ERbeta expression in T47D:A18 cells, PR expression in Ishikawa cells, but not AP activity in Ishikawa cells. These data suggest that linoleic acid from the fruits of Vitex agnus-castus can bind to estrogen receptors and induce certain estrogen inducible genes.