(Agnus castus)
Chasteberry has been shown to be helpful for menstrual irregularities including dysmenorrhea, secondary amenorrhea, metrorrhagia, oligomenorrhea, and polymenorrhea. It has been used for symptoms of menopause, premenstrual syndrome (PMS) including cyclical mastalgia, luteal-phase dysfunction (corpus luteum insufficiency), and other symptoms; female infertility, preventing miscarriage in patients with progesterone insufficiency, controlling postpartum bleeding, aiding in expulsion of the placenta, increasing lactation, and treating fibrocystic breasts.
Additionally it has been used for promoting urination, treating benign prostatic hyperplasia (BPH).
Chasteberry can also be of some help in treating acne, nervousness, dementia, rheumatic conditions, colds, dyspepsia, spleen disorders, headaches, migraine, eye pain, body inflammation and swelling.
The applicable parts of the chasteberry tree are the fruit and seed. The active constituents of chasteberries are the essential oils, iridoid glycosides, flavonoids, and diterpenes. Although not generally considered key constituents, chasteberries also contain several essential fatty acids, including oleic acid, linoleic acid, palmitic acid, and stearic acid.
The therapeutic effects of chasteberry have primarily been attributed to its indirect effects on various neurotransmitters and hormones. Chasteberry seems to affect dopamine, and possibly acetylcholine and opioid receptors. Dopaminergic activity inhibits basal and thyrotropin-releasing hormone (TRH)-stimulated prolactin release. In women with hyperprolactinemia, chasteberry seems to suppress prolactin release. This may normalize luteal phase defects in the menstrual cycle.
In men, chasteberry's hormonal effects can be dose dependent. Some helping with prolactin release.
Chasteberry appears to be selective for beta estrogen receptors. The beta estrogen receptor predominates in the heart, vasculature, bone, and bladder. Other preliminary research suggests that chasteberry might inhibit the growth of breast cancer cells and other cancer cells such as ovarian, cervical, gastric, colon, and lung.
In addition to hormonal effects, essential oils of chasteberry also seem to have antibacterial and antifungal effects. Extracts of chasteberry have moderate in vitro activity against a variety of gram-negative and gram-positive bacteria.
Other preliminary research suggests chasteberry might have analgesic and antihistaminic activity.
Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS.
Webster DE, Lu J, Chen SN, Farnsworth NR, Wang ZJ.
Department of Biopharmaceutical Sciences, College of Pharmacy, 833 South Woods Street, Room 335, University of Illinois, Chicago, IL 60612, USA.
The dried ripe fruit of Vitex agnus-castus L. (VAC) is widely used for the treatment of premenstrual syndrome (PMS). A previous study reported that extracts of VAC showed affinity to opiate receptors; however, functional activity was not determined. We tested two different VAC extracts in receptor binding and functional assays. Our objectives were: (1) to confirm the opiate affinity; (2) to rule out interference by free fatty acids (FFA); (3) to determine the mode of action of VAC at the mu-opiate receptor. Methanol extracts of VAC were prepared either before (VAC-M1) or after (VAC-M2) extraction with petroleum ether to remove fatty acids. Both extracts showed significant affinities to the mu-opiate receptor, as indicated by the concentration-dependent displacement of [3H]DAMGO binding in Chinese hamster ovary (CHO)-human mu-opiate receptor (hMOR) cells. The IC50 values were estimated to be 159.8 microg/ml (VAC-M1) and 69.5 microg/ml (VAC-M2). Since the defatted extract not only retained, but exhibited a higher affinity (p<0.001), it argued against significant interference by fatty acids. In an assay to determine receptor activation, VAC-M1 and VAC-M2 stimulated [35S]GTPgammaS binding by 41 and 61% (p<0.001), respectively. These results suggested for the first time that VAC acted as an agonist at the mu-opiate receptor, supporting its beneficial action in PMS.
A Vitex agnus-castus extract inhibits cell growth and induces apoptosis in prostate epithelial cell lines.
Weisskopf M, Schaffner W, Jundt G, Sulser T, Wyler S, Tullberg-Reinert H.
Institute of Pharmaceutical Biology, University of Basel, Schönbeinstrasse 40, 4003 Basel, Switzerland.
Extracts of Vitex agnus-castus fruits (VACF) are described to have beneficial effects on disorders related to hyperprolactinemia (cycle disorders, premenstrual syndrome). A VACF extract has recently been shown to exhibit antitumor activities in different human cancer cell lines. In the present study, we explored the antiproliferative effects of a VACF extract with a particular focus on apoptosis-inducing and potential cytotoxic effects. Three different human prostate epithelial cell lines (BPH-1, LNCaP, PC-3) representing different disease stages and androgen responsiveness were chosen. The action of VACF on cell viability was assessed using the WST-8-tetrazolium assay. Cell proliferation in cells receiving VACF alone or in combination with a pan-caspase inhibitor (Z-VAD-fmk) was quantified using a Crystal Violet assay. Flow cytometric cell cycle analysis and measurement of DNA fragmentation using an ELISA method were used for studying the induction of apoptosis. Lactate dehydrogenase (LDH) activity was determined as a marker of cytotoxicity. The extract inhibited proliferation of all three cell lines in a concentration-dependent manner with IC (50) values below 10 microg/mL after treatment for 48 h. Cell cycle analysis and DNA fragmentation assays suggest that part of the cells were undergoing apoptosis. The VACF-induced decrease in cell number was partially inhibited by Z-VAD-fmk, indicating a caspase-dependent apoptotic cell death. However, the concentration-dependent LDH activity of VACF treated cells indicated cytotoxic effects as well. These data suggest that VACF contains components that inhibit proliferation and induce apoptosis in human prostate epithelial cell lines. The extract may be useful for the prevention and/or treatment not only of benign prostatic hyperplasia but also of human prostate cancer.
Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study.
Halaska M, Beles P, Gorkow C, Sieder C.
Department of Gynecology and Obstetrics, Charles University of Prague, U Nemocnice 2, 128 00 Praha 2, Czech Republic.
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 x 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.
Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS).
Berger D, Schaffner W, Schrader E, Meier B, Brattström A.
Institut Pharmazeutische Biologie, Universität Basel, Witterswil, Schweiz.
In a prospective, multicentre trial the efficacy of an Vitex agnus castus L extract Ze 440 was investigated in 50 patients with pre-menstrual syndrome (PMS). The patients were treated daily with one tablet (20 mg native extract) during three menstrual cycles. 43 patients completed the study protocol which encompassed 8 menstrual cycles (2 baseline, 3 treatment and 3 post-treatment). 13/43 patients were receiving concomitant oral contraceptives. 6 patients did not complete the study for reasons not related to study medication, and one patient complained of fatigue possibly related to study medication. All evaluated patients took at least 85% of the prescribed medication. The main effect parameter was the validated Moos' menstrual distress questionnaire (MMDQ), and secondary parameters were a visual analogue scale (VAS; self-assessment) and a global impression scale (GI, self-assessment). The study population was homogenous in age (31.3+/-7.7 years) weight (58.9+/-6.9 kg) and cycle length (28.4+/-0.3 d). The diagnosis was according to DMS-III. At the end of the study, PMS-related symptoms were reduced by treatment. There was a significant score reduction (42.5%) of the MMDQ as the main effect parameter (p<0.001). Symptoms gradually returned after treatment cessation. However, a difference from baseline remained (20%; p<0.001) up to 3 cycles thereafter. 20/43 patients were considered "responders", with a reduction in MMDQ score by at least 50% relative to baseline. At baseline, the VAS score was elevated in the late luteal phase and low at the follicular phase, as expected. During treatment, VAS score decreased in the late luteal phase (47.2%; p<0.01) and remained 21.7% (p<0.001) below baseline after 3 cycles post-cessation of treatment. The low VAS score within the follicular phase remained unchanged over the whole observation period. 38 patients judged the global efficacy moderate to excellent, 5 patients indicated no global efficacy. The number of days patients sustained PMS symptoms was reduced slightly from 7.5 to 6. Resting levels of blood prolactin remained within the physiological range throughout. No differences were seen between patients on or off oral contraceptives. 20 patients reported 37 adverse events (AE). No serious AE were reported. One patint withdrew after four days of treatment due to fatigue and headache. Laboratory safety control parameters were not affected. In conclusion, patients with PMS can be treated successfully with Vitex agnus-castus extract Ze 440, as indicated by clear improvement in the main effect parameter during treatment and the gradual return after cessation of treatment. The main response to treatment seems related to symptomatic relief rather than to the duration of the syndrome.