by Michelle Shasha
Centuries ago, the lilac flowers of Vitex agnus-castus L. were a common sight on riverbanks in the lower foothills and valleys of Mediterranean Europe and Central Asia. The berries of the plant have been used as a herbal remedy since antiquity and are believed to treat an array of female-related conditions amongst other ailments. Some modern research supports ancient wisdom; across Europe, agnus-castus extracts have been formulated into medicines for the treatment of menstrual cycle abnormalities and premenstrual symptoms. More research is required to elucidate the basis of the herb’s other traditional uses and to understand its therapeutic mechanisms so that it can be better characterised as a medicine. The herb is generally well-tolerated, working in its favour as a pharmaceutical candidate for the treatment of other endocrinological and gynaecological conditions.
What is it?
Vitex agnus-castus L. belongs to the Vitex genus and is a member of the mint family (Lamiaceae). Native to Europe and Central Asia, the perennial shrub grows 5-15 ft tall and can sprawl 15-20 ft wide (Daniele, et al., 2005; Nor Hisham Shah & Bridgen, 2016). It is a favourite of gardeners for its attractive foliage and began to appear in English gardens as early as 1570 (Kent, 1831). Like Cannabis sativa L., the finger-shaped leaves of the deciduous bush are opposite and palmately compounded with 5–7 leaflets which produce a sage-like aroma and complete the legendary Moroccan spice blend ‘ras el hanout’ (Prance & Nesbitt, 2012). From summer to autumn, the long, pyramidal spires boast vibrant clusters of small lilac, pink or deep blue flowers, attracting butterflies, hummingbirds and bees. These fragrant flowers were traditionally made into perfumes. The medicinal properties of the plant are attributed to its reddish-brown drupes which appear soon after flowering. Each berry resembles the size of a black peppercorn and bears up to four seeds with a similar pungent taste (Nor Hisham Shah & Bridgen, 2016).
The name of a plant often alludes to its traditional uses. The genus name Vitex was first applied by Pliny the Elder. Vitex derives from the Latin vieo (to weave), signifying the once-common use of the tough, flexible branches in wickerwork (Quattrocchi, 2012).
The species name, agnus-castus – Latin for ‘chaste lamb’ – is a testimony to one of the most ancient legends about the plant. Agnus (lamb) was likely acquired from a historical misinterpretation of the original Greek name, ágnos (chaste), which was first applied by Dioscorides (Bohnert & Hahn, 1990). Likewise, the plant is commonly referred to as the chaste tree. Throughout the middle ages, chaste tree berries, or chasteberries, were believed to lessen sexual desire. Their anaphrodisiac properties, combined with their pungent taste, merited their place in monastic kitchens where they served as a cheap alternative to black pepper and earned the title ‘monk’s pepper’ (Odenthal, 1998).
Another synonym, ‘Abraham’s balm’, possibly has a Biblical connotation. The story of the Binding of Isaac relates that Abraham was commanded to sacrifice his son. However, he was stopped by an angel before he proceeded. Instead, he sacrificed a ram that was ‘caught in the thicket by his horns’ (Genesis 22:13)to symbolise his devotion to God. Jewish tradition deems this bush to be Vitex agnus-castus. This may indeed be referenced by the Latin word agnus (Gold, 2020). Others claim that Abraham’s wife, Sarah, was able to overcome her barrenness by using this plant.
What does it do?
From fables to pharmacies
Ironically, while the seeds were believed to repress sexual desire, the chasteberry has been used for centuries to treat an array of female-related conditions and enhance fertility. The works of Hippocrates, Pliny and Dioscorides reflect that during early Roman and Greek periods agnus-castus was highly revered. In the 4th century B.C., Hippocrates, esteemed as the ‘father of medicine’, recommended the herb for injuries, inflammation, enlargement of the spleen and to promote the departure of the placenta (Christie & Walker, 1997).
Pliny the Elder documented the use of agnus-castus by Athenian women during the Thesmophoria (Barceloux, 2008). During this three-day festival, the women would pay tribute to the cycles of renewal and the Greek goddess Demeter, and cover their beds with the leaves of the chaste tree to increase fertility (Jones, 1964). Perhaps, as only women partook in this festivity, agnus-castus became associated with chastity rather than fertility. Pliny wrote that the berries taste like wine, and recommended drinking a concoction of the soaked berries to reduce fevers, stimulate perspiration and treat snake bites (Jones, 1964).
Dioscorides, perhaps the most reliable of the ancient herbalists, wrote more in his De Materia Medica about agnus-castus than any other of the hundreds of herbs that he included in his works. Remarkably, his documentation of the plant’s medicinal properties resembles modern clinical evidence (Hobbs, 1991). He accounted that “it both brings down the milk and expels ye menstrua-being drank…in wine [and]…a decoction of the seed [is for] inflammation about the womb”,recommending the herb to initiate lactation and menstruation and to soothe gynaecological inflammation (Gunther, 1934). Contrary to his predecessors, he noted that the herb is futile for treating inflammation, wounds and venomous bites (Hobbs, 1991).
Agnus-castus was equally prized in the Middle East where it was known as Faqad, banjakusht or fanjackusht. During the ‘Golden age of Arabic science’, Al Kindi (9th century AD) wrote that it was sold in the bazaars and used for several female conditions and as a calming medicine for hysteria (Hamarneh, 1967).
Between the 16th-17th century, Dodoens and Gerard, amongst others of the great Renaissance herbalists recommended chasteberry as a remedy for digestive, liver and gynaecological ailments, often quoting Dioscorides (Gerard, 1975). The cherished remedy was included in some of the European pharmacopoeias, including the influential first Pharmacopeia Londinesis of 1618 (Daniele, et al., 2005; Hobbs, 1991). Yet, its popularity soon waned, and its status was dropped. By 1733, the remedy was described as “not now in esteem, or scarce ever made or used in the shops” (Padmalatha, et al., 2009).
Since the first clinical work on its galactagogue activity in 1953, the remedial herb has seen a resurgence in its popularity in England and other parts of Europe (Bautze, 1953). Several agnus-castus preparations are currently approved as a Traditional Herbal Medicinal Product under the Traditional Herbal Registration (THR) scheme for premenstrual symptoms. The herb is commonly prescribed by herbalists and is often present on the shelves of pharmacies and health food stores.
Are its uses clinically proven?
For herbs to be formulated into pharmaceuticals, their efficacy for the desired purpose and their safety profiles must be demonstrated. Modern clinical evidence indicates the effectiveness of agnus-castus in treating premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), cyclical mastalgia, latent hyperprolactinemia and polycystic ovary syndrome (PCOS).
PMS is a source of distress for many women. It is associated with a wide variety of symptoms including migraines, bloating, irritability and fatigue. Luckily, systematic reviews of randomised controlled trials have found Vitex agnus-castus to outperform placebos and dietary supplements in treating PMS (Cerqueira, et al., 2017; van Die, et al., 2013; Verkaik, et al., 2017).Another study reported its effectiveness in treating late-perimenopausal PMS-like symptoms (van Die, et al., 2009). A dose-dependent effect for a proprietary preparation of agnus-castus in PMS has been described, noting 20 mg of the ethanolic extract to be an effective dose (Schellenberg, et al., 2012). As recommended by Dioscorides, evidence from one study suggests that the herb specifically soothes migraines symptomatic of PMS (Ambrosini, et al., 2012). Findings regarding other symptoms appear to be inconsistent. Agnus-castus has also proven to be beneficial for alleviating physical symptoms of PMDD, a severe and often debilitating derivative of PMS (Atmaca, et al., 2003; Ciotta, et al., 2011).
High blood levels of prolactin, namely hyperprolactinaemia, is linked to menstrual abnormalities and excessive lactation (Serri, et al., 2003). Agnus-castus reduces prolactin secretion in latent hyperprolactinemia following a three-month treatment period (Milewicz, et al., 1993). Evidence from another study supports its effectiveness in relieving breast pain in women with cyclic mastalgia caused by latent hyperprolactinemia (Halaska, et al., 1998).
PCOS, another endocrinological disorder common amongst females, can involve a diverse array of symptoms including oligomenorrhea (infrequent menstruation), amenorrhea (absence of menstruation), hirsutism and weight gain. The syndrome is linked to a number of imbalances which usually spur an excess of male sex hormones including DHEA-S, termed hyperandrogenism. A clinical study has revealed that agnus-castus evokes effects similar to that of low dose oestrogen on the normalisation of the menstrual cycle and DHEA-S levels in women with PCOS (Shahnazi, et al., 2016).
Despite small sample sizes in some studies, current literature appears to demonstrate the tolerability and efficacy of Vitex agnus-castus in the treatment of some premenstrual and menstrual disorders (van Die, et al., 2013). Further research into agnus-castus for these conditions would benefit from more rigorous methodology and common endpoints to ultimately inform doctors and pharmacists.
Good quality clinical evidence is lacking for the herb’s relief of menopausal symptoms. 1869 (77.3%) participants of a questionnaire reported some degree of its’ effectiveness in treating climacteric symptoms (Chopin, 2003). Hence, robust clinical trials exploring its effects may prove profitable. As of now, other traditional medicinal uses of the plant, including its ability to treat inflammation, epilepsy and osteoporosis remain debatable, being supported by myths rather than meticulous laboratory studies.
Besides the hormone-balancing effect of the herb, its sage-like scent is believed to repel mosquitos amongst other pesky arthropods. Preliminary research has noted that when applied to the skin, chasteberry seed extracts are highly efficacious for repelling mosquitos, ticks, fleas and biting flies (Mehlhorn, et al., 2005). Further investigations may provide alternative and potentially safer formulations to protect against invertebrate transmitted diseases.
How does it work?
In common with many medicinal herbs, neither the pharmacologically active components of agnus-castus nor its mechanisms of therapeutic action are precisely defined. The remedial properties associated with the herb are attributed to interactions between its collective chemical components. Given this, the whole extract of the fruit is considered necessary to confer its medicinal benefits.
The diterpene constituents, including roundiferan, viteagnusin and vitexilactone, are thought to play an essential role in the pharmacological activity of the berries (Meier, et al., 2000). Iridoid glycosides present include aucubin, eurostide and agnuside. Bornyl acetate, limonene, 1,8-cineol, α- and β-pinene are the primary essential oils of the berries and provide their sweet fragrance (Edwards, et al., 2015). The major flavonoids, including casticin, orientin, and vitexin, are responsible for the dark red pigmentation and antioxidising properties of the fruit (Hajdú, et al., 2007). Chasteberries also contain phytosterols such as β-sitosterol and stigmasterol; these phytochemicals are similar to cholesterol and are the precursors of steroidal hormones such as oestrogen, progesterone and testosterone (Asdadi, et al., 2014). Agnuside or casticin often serve as a reference standard for assessing the potency and authenticity of agnus-castus extracts (Edwards, et al., 2015).
Mechanisms of action
Agnus-castus is believed to act on the pituitary gland and hypothalamus. Perhaps the herb effectively treats a range of ailments as its activity ‘starts from the top’. Several mechanisms for its therapeutic action have been proposed. The most explored mechanism involves inhibitory activity on dopamine receptor binding. Dopamine receptors are prominent in the central nervous system and are instrumental in the proper function of the neurotransmitter, dopamine, which modulates the release of sex hormones and mood.
Isolated diterpene constituents of agnus-castus, specifically roundifuran, have been shown to inhibit prolactin secretion in rat pituitary cells due to dopaminergic activity (Sliutz, et al., 1993). As elevated prolactin levels corelate with excessive lactation, this may motivate the herbs use in treating slight hyperprolactinemia (Nasri, et al., 2007; Schneider, et al., 1983). The dopaminergic activity of agnus-castus also inhibits testosterone secretion, supporting the herb’s efficacy in treating hyperandrogenic conditions (Arentz, et al., 2014; Nasri, et al., 2007). A corresponding increase in progesterone levels may explain the herb’s remedial effects on PMS-like and menopausal symptoms, in addition to its affiliation with miscarriage prevention, (Gardner & McGuffin, 2013). In other words, agnus-castus works to harmonise our sex hormones, changing the ratio of prolactin, testosterone and progesterone to favour progesterone and regulate awry menstrual cycles. Additionally, modulation of dopamine activity may be linked to the mitigation of mood swings associated with PMS and menopause (van Die, et al., 2009).
In vitro studies have also indicated opiate effects of agnus-castus. The opiate system consists of μ, δ, and κ opiate receptors as well as endogenous opiate peptides such as β-endorphin which regulates the menstrual cycle via inhibition of the hypothalamus–pituitary–adrenal axis (HPA). Dopamine has been found to potentiate the activity of the endogenous opioid system on thermoregulation in postmenopausal women (Cagnacci, et al., 1989). Thus, the dopaminergic activity of agnus-castus may be responsible for alleviating hot flushes symptomatic of menopause. Various agnus-castus flavonoids have exhibited binding activity on μ and δ-opiate receptors in Chinese hamster ovary cells (Webster, et al., 2006; Webster, et al., 2011). Consequent induced opioid activity may alter pain perception and regulate mood.
Other studies have revealed antioxidant properties of agnus-castus extracts, with a positive correlation between the strength of activity and flavonoid content (Sarikurkcu, et al., 2009). Antioxidants attenuate oxidative damage, which describes the cumulative, non-specific degeneration of physiological processes. Such damage essentially originates from an imbalance of free radicals and antioxidants caused by various internal and external factors including environmental stresses. Prolonged oxidative damage is believed to elicit chronic inflammation and consequently, chronic diseases. Hence, an excess of free radicals may motivate various reproductive disorders including PCOS and unexplained infertility (Agarwal, et al., 2012). Agnus-castus may provide a remedy for these conditions by intercepting free radicals to curtail oxidative damage and by stimulating the body’s self-repair mechanisms.
Is it safe?
Agnus-castus has been used for centuries without serious known side effects and has been deemed safe by a number of studies (Ganapaty & Vidyadhar, 2005). Adverse effects are thought to be minor and temporary and may include headache, nausea and indigestion. As the active ingredients in agnus-castus extract are not well defined, there is little data on the toxicokinetics of these compounds. Current data does not acknowledge clinically significant drug interactions with the use of the herb. Theoretically, agnus-castus extracts may suppress milk production or interact with dopamine antagonists including mood-altering and hormone-balancing medicines. Despite the misleading notion that herbal medicines are natural and are therefore safe, precautions should be taken, especially by those taking other medications and pregnant or lactating women (Daniele, et al., 2005; Dugoua, et al., 2008).
Vitex agnus-castus exemplifies a plant which has its traditional uses backed by modern science. Studies have demonstrated its efficacy for several female-related conditions. The age-old remedy certainly warrants further research in the realm of hormonal imbalances, especially as it is generally well-tolerated. The chasteberry may ease symptoms of other endocrinological troubles, and as believed by the Athenians, may indeed boost female fertility (Rafieian-Kopaei & Movahedi, 2017). It should be noted that, like all herbs, medicinal properties are more likely to be experienced with high-quality extracts. The THR logo, granted to herbal medicines which have met approved quality and safety criteria, indicates substantial quality for products on the market.
In this essay we do not advise or recommend herbs for medicinal or health use. This information is intended for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflet (i.e. for THR products).
© Michelle Shasha, 2020. All rights reserved.
Michelle Shasha is a neuroscientist currently studying for her M.Sc. in Medicinal Natural Products and Phytochemistry at the UCL School of Pharmacy. Her focus is on safe and efficacious herbal remedies for neurological and endocrinological disorders. To contact Michelle, please use the contact form on this website.
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