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Vitex agnus-castus

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Background & General Info

Vitex agnus-castus is a deciduous shrub belonging to the mostly flowering family of Verbenaceae and is a native inhabitant of the European, Mediterranean, and Central Asian regions. [1] The genus name Vitex comes from the Latin term vieo, which means “to weave or to tie up” since this shrub is traditionally utilized in basketry. [2] The species agnus-castus on the other hand derives from Greek and Latin terms “agnós” and “castus,” which both together translate to “chaste,” pertaining to the plant’s putative libido-reducing ability, especially its seeds, ingested as a potion. [3] Vitex agnus-castus also goes by common names such as monk’s pepper and chaste tree as a reference to the early use of the plant’s berries by monks during the Middle Ages to suppress their sexual desire and hence to help keep their celibacy. [1]

The peppery dried fruits are the most frequently employed medicinal form of the plant and to date has been fashioned in a variety of pharmaceutical preparations, such as tinctures, fluid extracts, tablets, and homoeopathic forms. [4]



Botany

Vitex agnus-castus distinctively grows fast in an upright, multi-branching manner, reaching a height of 15–25 feet at maturity. The aromatic leaves are pale green above but grayish white underneath. From late spring to fall, the plant’s fragrant, showy, tiny lavender-blue flowers bloom in spikes at branch ends and leaf joints. [5] The oval to almost globular, blackish-brown fruit has a diameter of up to 5 mm, with greenish-gray, finely pubescent persistent calyx that terminates with 4–5 short teeth and almost encases the entire fruit’s surface. The fruit’s pericarp increasingly becomes hardened up to the endocarp, and the style scar often remains visible. A transverse section of the fruit shows four locules that each hold an elongated seed. [3]

History & Traditional Use

Chaste tree has been used for centuries, dating back to the ancient Greeks and Romans, and its medicinal therapeutic utility has long been recognized by practitioners and the public. In certain Anglo-American and European traditional medicinal practice, chaste tree is commonly prescribed as a well-accepted herbal treatment for a wide array of female reproductive conditions. [4] Dioscorides, a prominent, well-respected Greek pharmacologist of antiquity, mentioned its use as a medicinal plant. [3]

In European counties, an array of Vitex agnus-castus products are being marketed under the plant’s well-established traditional use, with some Vitex agnus-castus herbal preparations being in the markets of Germany and Austria for over 30 years. [3] The aromatic leaves and fruits can be consumed as flavor and spice in food; [6][7] the fruits in particular were in earlier times utilized as a substitute for pepper in regions from Italy to Eastern Georgia—a culinary use that still persists to be reflected in the local culture, for instance, in some Italian synonyms of chaste tree’s name (“albero del pepe,” “pepe falso”). [6] In Iranian traditional and folk medicine, chaste tree fruits are valued as a hormone-like remedy for easing menstrual concerns and as a mild tranquilizer and aid to digestion. [7]

General Herbal Uses

European and North American herbalists recommend Vitex agnus-castus as traditional treatment of acne, digestive complaints, menstrual irregularities, premenstrual syndrome, mastalgia, and infertility, as well as an agent that supports lactation. [1] Vitex agnus-castus is conventionally employed as an emmenagogue, sedative, anaphrodisiac, and galactagogue, whereas the ethanolic extract derived from it can be used as a homeopathic drug to treat or manage impotence and central nervous system disorders. The flowers of this plant are medicinally valued as an effective remedy for diarrhea and liver disorders, and the powder obtained from its green parts is applied as an internal antihemorrhagic agent. [8]



Constituents/Active Components

Phytochemical studies indicate volatile oils, flavonoids, coumarins, and terpenes as the primary constituents of chaste tree. Caryophylle oxide (24.9%), n-hexadecane (12.5%), and α-terpenyl acetate (11.6%) were found as the main components of Vitex agnus-castus volatile oil in the investigation of Ghannadi et al. (2012). [7]

A chemical composition assessment by Stojković et al. (2011) revealed sabinene and 1,8-cineole as the chief constituents of the oil from unripe and ripe fruits, with the leaves characterized by a large quantity of 1,8-cineole (22.0%) as well. The results of chemical analysis of different chaste tree parts are presented in the table below, of which 50 compounds were identified (98.5% of total oil) in the unripe fruit oil and 51 components in the ripe fruit oil (99.2%). [6]

Vitex agnus-castus Compounds

Medicinal/Scientific Research

Premenstrual Symptoms

Extracts acquired from Vitex agnus-castus fruits are profoundly prescribed as treatment of female reproductive disorders, such as premenstrual symptoms and associated cyclic mastalgia, premenstrual dysphoric disorder, lactation problems, low fertility, and menopause-related complaints. Clinically, extracts of Vitex agnus-castus prove to be helpful in relieving cycle irregularities. [9]The plant’s effects have been likened to those of the corpus luteum, and its mechanism of action possibly lies in its modulation of stress-induced prolactin secretion via dopamine, without directly influencing luteinizing hormone or follicle-stimulating hormone, and its binding to opioid receptors, β endorphins, and neuroactive flavonoids. [10]

Evidences from double-blind placebo-controlled trials as well as several less rigidly controlled studies point out the therapeutic effect of Vitex agnus-castus extract on premenstrual mastodynia and other psychic and somatic symptoms of premenstrual syndrome. Premenstrual mastodynia, or pain in the breast, possibly results from a latent hyperprolactinemia due to the release of excessive physiologic amounts of prolactin during stressful situations and mammary gland-stimulating deep sleep phases. Prior to menstruation, unphysiological prolactin elevates to levels that can be misinterpreted as prolactinomas. Such increased prolactin levels were shown to be reversed by Vitex agnus-castus extract administered in patients in a double-blind, placebo-controlled clinical study, and dopaminergic compounds present in Vitex agnus-castus, particularly diterpenes, appear to act as prolactin-suppressive principles that bind to recombinant dopamine 2 receptor protein in animal experiments. By binding to these dopamine 2 receptors, Vitex agnus-castus extracts exert a dopaminergic activity, leading to prolactin inhibition. [9]

A 2013 systematic review accumulated encouraging findings from randomized, controlled trials of generally moderate to high methodological quality on the efficacy and safety of Vitex agnus-castus extracts as treatment of premenstrual syndrome, premenstrual dysphoric disorder, and latent hyperprolactinemia. From a thorough search in eight databases and with methodological quality evaluated based on the Cochrane risk of bias and Jadad scales, the review obtained results from twelve randomized, controlled trials about Vitex agnus-castus preparations, eight of which examined premenstrual syndrome; two, premenstrual dysphoric disorder; and two, latent hyperprolactinemia. In this systematic review, eight trials confirmed the effectiveness of chaste tree extracts in managing premenstrual syndrome, compared to placebo, pyridoxine, and magnesium oxide. Adverse events with chaste tree intervention were mild and largely rare. [4]

According the study results of a 2009 prospective, randomized, multicenter, double-blind, placebo-controlled study, Vitex agnus-castus extract (VAC BNO 1095 equivalent to 40 mg herbal drug) is safe, well tolerated, and effective in relieving moderate to severe premenstrual syndrome among Chinese women treated. The study involved 217 eligible Chinese women who were randomly divided to the treatment group administered with the Vitex agnus-castus extract for up to three cycles and the placebo group. For the experimental group, the mean total premenstrual syndrome diary score significantly declined from 29.23 at baseline to 6.41 during the third cycle, whereas for the placebo group, this score decreased from 28.14 to 12.64. Comparing the difference in mean diary scores from baseline to the third cycle, that of the treated group (22.71 ± 10.33) was significantly lower than that of the placebo group (15.50 ± 12.94, p<0.0001), with no observed serious adverse events in both groups. [11] Likewise, an earlier 2001 randomized, double-blind, placebo-controlled study confirmed the efficacy and tolerability of dry extract of chaste tree fruits as remedial reliever of symptoms of premenstrual syndrome. In general medicine community clinics, one tablet of 20 mg dry Vitex agnus-castus extract and matching placebo were offered for three consecutive cycles to a total of 170 women (active, 86; placebo, 84) with mean cycle length and mean menses duration of 28 days and 4.5 days, respectively. The results indicated a better improvement in main efficacy variables (i.e., difference from baseline to end of the third cycle in women’s self-assessment of irritability, mood alteration, anger, headache, and breast fullness) and in secondary efficacy variables (i.e., changes in responder rate and in clinical global impression as regards severity of condition, global improvement, and risk or benefit) in the experimental group than the placebo group (p < 0.001). Moreover, the responder rates were 52% and 24% for the experimental and placebo groups, respectively, with only seven women reporting mild adverse events that did not lead to discontinuation of treatment. [10]

Despite most studies failing to satisfy some methodological criteria, randomized, double-blind, placebo-controlled trials have shown that pyridoxine, or vitamin B6, beneficially relieves overall premenstrual and depressive symptoms in women with premenstrual syndrome. [12] Lauritzen et al. (1997) conducted a randomized, controlled trial to compare the efficacy and tolerability of Agnolyt®, a solid formulation of chaste tree in capsular form, and those of pyridoxine in women diagnosed with premenstrual tension syndrome. For up to three treatment cycles, one Vitex agnus-castus capsule and one placebo capsule were administered to 90 study participants daily; two capsules of pyridoxine, on the other hand, were provided to 85 individuals. As regards therapeutic response, both chaste tree and pyridoxine treatments decreased the score points on the premenstrual tension syndrome scale, from 15.2 to 5.1 (−47.4%) for Vitex agnus-castus and from 11.9 to 5.1 (−48%) for pyridoxine. A recording of distinctive premenstrual syndrome complaints indicated a superior alleviation of breast tenderness, edema, inner tension, headache, constipation, and depression for the Vitex agnus-castus treatment in comparison with pyridoxine. Upon trial completion, physicians and patients themselves were asked to evaluate the efficacy of treatment; Vitex agnus-castus and pyridoxine treatments were rated as 24.5% and 12.1% by the investigators, with investigator rating for Vitex agnus-castus treatment being considered as excellent. The patients’ assessment also determined absence of complaints in 36.1% of cases in chaste tree treatment group and 21.3% in the pyridoxine treatment group. [13]

A 2000 multicenter open trial without control likewise evaluated the efficacy and tolerance of a solid preparation from Vitex agnus-castus fruit extract in 1634 patients under routine medical conditions and suffering from premenstrual syndrome. After three menstrual cycles, majority of patients (93%) verbalized a reduction in the number of symptoms or even an absence of premenstrual syndrome complaints, with such effect extending within all symptom complexes and correlated with global assessment of therapeutic efficacy. Furthermore, most physicians (85%) rated the efficacy of chaste tree fruit extract as good or very good; similarly, majority of patients (81%) reported a “very much” or “much better” status after treatment. After 3 months of chaste tree fruit extract treatment, persisting complaints were categorized as mostly less severe per analysis of frequency and severity of mastodynia, which is the predominant symptom. With respect to tolerance, 94% of patients considered the Vitex agnus-castus extract treatment as good or very good, with no serious adverse drug reactions having been observed. [14][15]

Hyperprolactinemia

Again, owing to the dopaminergic effect of Vitex agnus-castus, it can be regarded as an efficient phytotherapeutic alternative in the treatment of mild hyperprolactinemia. [61] A 1993 German randomized double-blind study illustrated the effectiveness of a Vitex agnus-castus preparation (Strotan capsules), compared with placebo, as a treatment of luteal phase defects due to latent hyperprolactinemia. In this clinical study, one 20 mg Vitex agnus-castus capsule and placebo were consumed on a daily basis by 52 women suffering from luteal phase defects as a result of latent hyperprolactinemia, whose blood samples were acquired for hormonal analysis at days 5–8 and day 20 of the menstrual cycle before and after three months of therapy. The 3-month Vitex agnus-castus treatment significantly decreased the elevated pituitary prolactin release, normalized shortened length of luteal phases, and eliminated deficits in luteal phase progesterone synthesis. Furthermore, side effects were absent throughout the course of the study, although two study participants treated with the Vitex agnus-castus preparation got pregnant. [15] Sliutz et al. (1993) explained that Vitex agnus-castus extract and lisuride, a synthetic dopamine agonist and antiparkinson agent, both considerably suppress basal and thyrotropin-releasing hormone (TRH)-stimulated secretion of prolactin in rat pituitary cells in vitro, making both efficient phytotherapeutic therapies of hyperprolactinemia. [16]

Premenstrual Dysphoric Disorder

Based on evidence from several clinical trials, selective serotonin reuptake inhibitors (SSRIs) and Vitex agnus-castus extract are efficacious treatment of premenstrual dysphoric disorder. Atmaca, Kumru, and Tezcan (2003) compared the efficacies of both fluoxetine, an SSRI used as medication for depression or obsessive–compulsive disorder in adults, and of Vitex agnus-castus extract in 41 patients suffering from premenstrual dysphoric disorder according to DSM-IV. This single-blind, rater-blinded, prospective study divided the patients into groups taking either fluoxetine or Vitex agnus-castus extract for 2 months, with Penn daily symptom report (DSR), Hamilton depression rating scale (HAM-D), and clinical global impression–severity of illness (CGI-SI) scale, and clinical global impression–improvement (CGI-I) scale as outcome measures. The results demonstrated a similar percentage of patients responding favorably to fluoxetine (68.4%) and Vitex agnus-castus extract (57.9%) in terms of clinical improvement, suggesting that both fluoxetine and Vitex agnus-castus extract are excellent remedies in managing premenstrual dysphoric disorder. It should be noted that nevertheless fluoxetine was superior in dealing with psychological symptoms than the extract. [17]

Learning And Memory

Honari et al. (2012) demonstrated the therapeutic estrogen-like effect of Vitex agnus-castus on learning and memory disorders in ovariectomized rats. In this animal study, 42 ovariectomized female Wistar rats weighing 150 to 200 g were grouped into five clusters to receive respective oral treatments for three months after ovariectomy: a control group, an ovariectomy group, and three groups receiving Vitex agnus-castus extract at 8 mg/kg; Vitex agnus-castus extract at 80 mg/kg and estradiol valerate at 40 μg/kg; and tamoxifen at 100 μg/kg and Vitex agnus-castus extract at 80 mg/kg. With rat learning ability assessed through a shuttle box at the end of treatment period, the groups orally administered with 40 μg/kg of estradiol valerate and 8 and 80 mg/kg of Vitex agnus-castus extracts, as well as the control group, exhibited elevated level of “step through latency” (STLr) factor, with reverse results observed for “time spent in dark compartment” (TDC) factor. In rats treated with 80 mg/kg of Vitex agnus-castus extract alone did only the frequency of shock lessen, signifying conclusively that Vitex agnus-castus extract can potentially enhance memory of ovariectomized female rats. [18]

Antibacterial

The methanol extract of Vitex agnus-castus and its hexane, chloroform, ethyl acetate, and butanol fractions have been demonstrated to exert significant activity against various bacteria. Specifically, the crude methanolic extract of Vitex agnus-castus suppressed the growth of Salmonella typhi, with an inhibition zone of 12.5 mm, whereas its hexane fraction exhibited inhibitory activity against Bacillus cereus, Pseudomonas aeruginosa, and S. typhi. Both chloroform and butanolic fractions significantly inhibited B. cereus, Klebsiella pneumoniae, P. aeruginosa, and S. typhi; the ethyl acetate displayed antibacterial activity against K. pneumoniae, P. aeruginosa, and S. typhi. [8]

In the study of Ghannadi et al. (2012), essential oils of Pelargonium graveolens L'Her and Vitex agnus-castus L. expressed significant antibacterial activity against Salmonella enteritidis (PTCC 1091), P. aeruginosa (PTCC 1074), Staphylococcus aureus (PTCC 1112), and Bacillus subtilis (PTCC 1023), as screened by disc diffusion method. The volatile oil acquired after hydrodistillation of Vitex agnus-castus seeds had an average yield of 1% (w/v) based on dry weight. The susceptibility of the strains altered with the essential oils’ dilution in DMSO. The pure essential oils exhibited the most extensive inhibition zones and are regarded in this study as effective antimicrobial system compared with chloramphenicol and amoxicillin. S. aureus was found to be the most susceptible strain, with caryophyllene oxide being an important antibacterial component of Vitex agnus-castus volatile oil. [7] An antibacterial effect from Vitex agnus-castus oils had also been confirmed in the study of Stojković et al. (2011) wherein the most outstanding antibacterial activity was against Salmonella typhimurium in microdilution test for all chaste tree oils tested and Micrococcus flavus and B. subtilis were most sensitive to the effect of 1,8-cineole and α-pinene. In this study, all chaste tree oils examined displayed more or less similar antibacterial action, although the oil from the unripe fruits of chaste tree demonstrated slightly better activity against M. flavus, and were all effective in comparison to the commercial antibiotic streptomycin. [6]

Contraindications, Interactions, And Safety

There are no established interactions between chaste tree preparations and other drugs in humans; however, its use is best avoided when taking dopamine agonists and going through hormone replacement therapy as the current understanding of its mechanisms of action is still very limited. The mild, reversible, and infrequent side effects reported for the plant extracts consist of gastrointestinal upset, urticaria, fatigue, headache, dry mouth, tachycardia, nausea, and agitation in very few patients. [19]

In a 1997 randomized, controlled trial, adverse events such as gastrointestinal and lower abdominal complaints, skin manifestations, and transitory headache were observed in five patients receiving pyridoxine treatment and in twelve patients administered with Vitex agnus-castus capsules, with no serious adverse events detected. [13]

A 2008 systematic literature review on the use, safety, and pharmacology of chaste tree in pregnant and lactating women indicated poor evidence about the plant’s estrogenic and progesteronic, uterine-stimulating, and emmenagogue activities in this special population. There is also conflicting opinion whether chaste tree increases or decreases lactation based on theory and in vitro studies. [19] Overall, it is best to avoid the use of Vitex agnus-castus in knowingly pregnant and breastfeeding women because of the plant’s unknown effects during early pregnancy and probable hormonal effects through breast milk.

References:

[1] "Vitex agnus-castus," Alternative Medicine Review, vol. 14, no. 1, p. 67–70, 2009. http://www.altmedrev.com/publications/14/1/67.pdf

[2] U. Quattrocchi, CRC World Dictionary of Plant Names, vol. 1, New York: CRC Press, 2000, p. 91. https://www.crcpress.com/CRC-World-Dictionary-of-Plant-Names-Common-Names-Scientific-Names-Eponyms/Quattrocchi/p/book/9780849326738

[3] EMA/HMPC, "Assessment report on Vitex agnus-castus L., fructus," 25 November 2010. http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2011/08/WC500110098.pdf

[4] M. D. van Die, H. G. Burger, H. J. Teede and K. M. Bone, "Vitex agnus-castus extracts for female reproductive disorders: A systematic review of clinical trials," Planta Medica, vol. 79, no. 7, p. 562–575, 2013. https://www.ncbi.nlm.nih.gov/pubmed/23136064

[5] E. California, "Vitex agnus-castus," 2013. http://www.ecolandscape.org/plantProfiles/Vitex_agnus_castus.pdf

[6] D. Stojković, M. Soković, J. Glamoclija, A. Dzamic, A. Ciric, M. Ristić and D. Grubišić, "Chemical composition and antimicrobial activity of Vitex agnus-castus L. fruits and leaves essential oils," Food Chemistry, vol. 128, no. 4, p. 1017–1022, 2011. https://www.researchgate.net/publication/232393717

[7] A. Ghannadi, M. Bagherinejad, D. Abedi, M. Jalali, B. Absalan and N. Sadeghi, "Antibacterial activity and composition of essential oils from Pelargonium graveolens L'Her and Vitex agnus-castus L," Iranian Journal of Microbiology, vol. 4, no. 4, p. 171–176, 2012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507305/

[8] Azizuddin and M. I. Choudhary, "Antibacterial, phytotoxic, insecticidal and cytotoxic potential of Vitex agnus-castus," Journal of Medicinal Plants Research, vol. 5, no. 23, p. 5642–5645, 2011. http://www.academicjournals.org/journal/JMPR/article-full-text-pdf/78D192F17327

[9] W. Wuttke, H. Jarry, V. Christoffel, B. Spengler and D. Seidlová-Wuttke, "Chaste tree (Vitex agnus-castus)—pharmacology and clinical indications," Phytomedicine, vol. 10, no. 4, p. 348–357, 2003. https://www.ncbi.nlm.nih.gov/pubmed/12809367

[10] R. Schellenberg, "Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study," British Medical Journal, vol. 322, no. 7279, p. 134–137, 2001. https://www.ncbi.nlm.nih.gov/pubmed/11159568

[11] Z. He, R. Chen, Y. Zhou, et al., "Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China," Maturitas, vol. 63, no. 1, p. 99–103, 2009. https://www.ncbi.nlm.nih.gov/pubmed/11159568

[12] K. Wyatt, P. Dimmock, P. Jones and P. O'Brien, "Review: Vitamin B6 is beneficial in the premenstrual syndrome," Evidence-Based Medicine, vol. 4, no. 6, p. 182, 1999. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC27878/

[13] C. Lauritzen, H. Reuter, R. Repges, K. Böhnert and U. Schmidt, "Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine," Phytomedicine, vol. 4, no. 3, p. 183–189, 1997. https://www.ncbi.nlm.nih.gov/pubmed/23195474

[14] E. Loch, H. Selle and N. Boblitz, "Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus," Journal of Women's Health and Gender-Based Medicine, vol. 9, no. 3, p. 315–320, 2000. https://www.ncbi.nlm.nih.gov/pubmed/10787228

[15] A. Milewicz, E. Gejdel, H. Sworen, et al., "Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study," Arzneimittelforschung, vol. 43, no. 7, p. 752–756, 1993. https://www.ncbi.nlm.nih.gov/labs/articles/8369008/

[16] G. Sliutz, P. Speiser, A. Schultz, J. Spona and R. Zeillinger, "Agnus castus extracts inhibit prolactin secretion of rat pituitary cells," Hormone and Metabolic Research, vol. 25, no. 5, p. 253–255, 1993. https://www.ncbi.nlm.nih.gov/pubmed/8330858

[17] M. Atmaca, S. Kumru and E. Tezcan, "Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder," Human Psychopharmacology, vol. 18, no. 3, p. 191–195, 2003. https://www.ncbi.nlm.nih.gov/pubmed/12672170

[18] N. Honari, I. Pourabolli, E. Hakimi zadeh, A. Shamsizadeh, F. Amin and M. Allatavakoli, "Effect of Vitex agnus-castus extract on learning and memory in ovariectomized rats," Journal of Mazandaran University of Medical Sciences, vol. 22, no. 93, p. 2–10, 2012. https://www.ncbi.nlm.nih.gov/pubmed/26904176

[19] J. Dugoua, D. Seely, D. Perri, G. Koren and E. Mills, "Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation," Canadian Journal of Clinical Pharmacology, vol. 15, no. 1, p. e74–79, 2008. https://www.ncbi.nlm.nih.gov/pubmed/18204102

Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018

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