Natural sources and plants frame the promise of today’s advanced pharmaceutical and contribute to a large scope to the commercial medicate productions fabricated nowadays. Almost 25% of drugs endorsed around the world are inferred from plants. Herbs still frequently used instead of drug in health cares
(Wachtel-Galor et al., 2011). Over the past three decades, the use of herbal medicine has augmented significantly and at least 80% of people around the world depend on them for some part of primary healthcare (
Ekor, 2014). Herbal remedies have also been widely used in many developed countries and becoming mainstream in the UK and the rest of Europe, as well as in North America and Australia (
Anquez-Traxler, 2011). Based on the long history of using herbal perpetration on clinical issues of various indigenous societies, the success rate of creating new drug from natural herbal sources must be higher that from chemical perpetration
(Pan et al., 2013).
Vitex agnus castus (VAC) is one of the herbs used as a medicinal plant. It is considered a traditional herbal remedy, primarily used in Anglo-American and European practice for a variety of female reproductive dysfunction (
Van Die et al., 2013). It is derived from dried fruit of chastisea trees and since ancient Greece used as female boitincal health
(Wuttke et al., 2003). In Morocco, vitex agnus is regularly utilized in conventional medication for treatment of many medical situations such as diabetes, rheumatism, respiratory, stomach related tract, dermatological, genitourinary and glands disorders
(Berrani et al., 2018).
Vitex is often used to relieve the symptoms associated with female hormonal in-balances such as the depression, cramps, mood swings, water retention and weight gain. In European Medical practice and Herbalism, the Vitex recommended for uterine fibroid cysts and to assist alleviating the obnoxious side effects of menopause (
Hobbs 1991). VAC has historically been utilized in recovering several female dysfunctions encompassing premenstrual syndrome, menstrual disorders (dysmenorrhea, amenorrhea), corpus luteum insufficiency, infertility, hyper-prolactineamia, disrupted lactation, acne and menopause
(Daniele et al., 2005).
Vitex agnus castus L. is a little deciduous chaste tree that has been employed in ancient Egypt, Iran, Greece and Rome for various gynecological issues over 2500 years
(Niroumand et al., 2018). A variety of plant phytochemical including flavonoids and linoleic acid which may be responsible for the biological activities have been isolated from chasteberry
(Chen et al., 2011; Webster et al., 2011).
In Saudi Arabia, many women have menstrual cycle disturbances and menopausal dysfunction and many have polycystic ovary syndrome at young age.
Guraya, (2013). reported that many Saudi women have reproductive system problems such as PCOS in young age, delay in pregnancy, menstrual irregularity. Using Vitex is not common in Saudi tradition like other Arab countries. Recently, just few people used this herb for treating some infertility problems. So, this brief review to expand the use this herb and discuss the different usages, beneficials effects of this medicinal plant and touching on the side effects.
The literature published from (1990-2019) was reviewed using the database google, scholar, PubMed, research gate and Academia. The research was carried out using various terms such as
Vitex angnus castus, polycystic ovarian syndrome (PCOS), hormonal anomalies in female, menopause, the management of PCOS and management of menopause. All recovered articles were wisely evaluated and data were gotten.
Characteristics of plants
Vitex agnus-castus is a small tree that included in the family of Verbenaceae
(Ono et al., 2011; Rani and Sharma., 2013;
Rashed., 2013). The plant
Vitex agnus castus is a deciduous shrub that reaches a height of up to 5 m
(Berrani et al., 2018). The leaves appear like fingers with 5-7 finger-like leaflets and 7.5-10 cm in diameter (Fig 1)
(Niroumand et al., 2018). The leaves are arranged in opposite, with a lengthened petiole. The green leaflets are linear, lanceolate, toothed and dark on the top and grey below
(Ono et al., 2011). The flowers are fragrant with lilac, blue, pink, or white color
(Berrani et al., 2018). Fruits are berries which contains four seeds resemble to black pepper
(Niroumand et al., 2018). The skin of the fruits is hard and has a purple to a black color, yellowish inside and half covered by their green sage-calyces. It has aromatic and spicy scent and the flavor is warm and singular after maturation
(Berrani et al., 2018). This plant is viewed as one of a medicinal herbs because both the fruit berry and the dried leaves have been utilized in many therapeutic issues (
Mancho and Edwards., 2005;
Niroumand et al., 2018).
Botany and Natural Occurrence
Vitex agnus castus is affiliated to Verbenaceae family, commonly known as chaste tree and monk’s pepper
(Ono et al., 2011; Rani and Sharma., 2013). This tree grows in all Mediterranean regions, in tropical and subtropical regions (
Rashed, 2013) and in temperate zone (
Duymuş et al., 2014). VAC distributed not only the Mediterranean Region and Central Asia, but it also can be found in Southern Europe and cultivated in the various regions including the United States
(Ono et al., 2011; Li et al., 2013; Rani and Sharma., 2013).
The plant often found growing next to streams and it loves water, but it could be seen growing in dry, rocky spots on the Greek islands. (
Hobbs., 1991). VAC is growing in areas where the Mediterranean climate is dominant, rather rocky places, wetlands such as stream banks and valleys. VAC can also be found on limestone slopes, in sunny and warm areas (
Rajić et al., 2016).
Phytochemical compounds
There are different reports on the Phytochemical continents of VAC. Fruits, flowers and leaves of VAC are reported to contain different bioactive compounds (
Rajić et al., 2016). It includes Vitexlactam C, Vitexlactam B
(Li et al., 2013), essential fatty acids, volatile oil, alkaloid, progestins, flavonoids, iridoid glycosides
(Arokiyaraj et al., 2009), iridoids (
Rajić et al., 2016), two simple phenols
(Li et al., 2013), diterpenoids and phytosterodids which have antihistaminic, antioxidant anti-inflammatory, hepato-protective properties (
El-Nawasany., 2019).
Iridoid glycosides are mainly two (agnuside, aucubin)
(Li et al., 2013; Rajić et al., 2016). Flavonoids named as Casticin, luteolin7-methyl ether and luteolin 7-O-glucopyranoside
(Aissaoui et al., 2016), vitexin, kaempferol, quercetagetin (
Rajić et al., 2016), 5-hydroxy-3,6,7,42 -tetramethoxyflavone and artemetin
(Li et al., 2013). Progestins includes progesterone, hydroxy progesterone and androstenedione (
Rajić et al., 2016). Alkaloids such as viticin; volatile oil includes 1,8-cineol, limes, α-pinenes, β-pinenes. Essential fatty acids such as palmitic acid, oleic acid and stearic acid (
Rajić et al., 2016). The two simple phenolic are p-hydroxybenzoic acid and p-hydroxybenzoic acid glucose ester
(Li et al., 2013).
The main Chemical compounds of this plant include vitexin, casticin, agnuside, p- hydroxybenzoic acid, alkaloids, diterpenoids. Flavonoids, terpenoids, neolignans, one glyceride and phenolic compounds are found in its fruits (
Rafieian-Kopaei and Movahedi, 2017).
Traditional uses
The use of VAC in medicine has a long history. Hippocrates (460-370 BC), The ophrastos (371-287 BC) and Pedanius Dioscorides (90-40 BC) already reported it on the preparation. It was used to inhibit libido, diseases of the uterus, promote wound healing and in the Middle Ages to preserve the vow of chastity so it was called chastity mud and chaste tree (
Anwendung, 2009).
Since more than 2500 years, Vitex fruits have been linked to a number of gynecological issues in ancient Egypt, Greece, Iran and Rome. It was also used for its suspected libido suppression (
Roemheld Hamm, 2005). It has long tradition in outdated medicine, as a medicinal plant. It has been commonly used since 17
th century as a popular folk treatment for female reproductive dysfunction encompassing corpus luteum insufficiency, premenstrual syndrome (PMS), menopausal symptoms and inadequate milk production (
Duymuş et al., 2014). It is used as diuretic, digestive antifungal, against anxiety and stomachache in Anatolian folk medicine (
Kuruuzum_Uz et al., 2003). It has been utilized for reproductive disorders in female since Greek and Roman times. In 4
th century B.C., Hipocrates suggested the plant for treating injuries, inflammation and swelling of spleen.
(Daniele et al., 2005).
During the past 50, years, chasteberry in Europe has been commonly used in premenstrual syndrome (PMS), menstrual bleeding, menstrual disorders and uterine dysfunction. The German commission E accepts the application of VAC by family doctors and gynecologists for menstrual cycle disorders, cyclic breast pain and PMS (
Roemheld-Hamm, 2005).
Vitex fruits and leaves are ideal candidate as flavor and spice to be used in food and the berries as pepper alternative in Persian traditional medicine
(Li et al., 2013). The fruits have been suggested as hormone-like medication to improve menstrual disorders and as antiepileptic, carminative, energizer, anticonvulsant, tranquilizer agents and to recover the digestive dysfunction
(Ghannadi et al., 2012). According to ethnomedicine of various nations, this shrub is utilized to relieve menstrual pain, spasmodic dysmenorrhea, insufficient lactation, treatment of acne and eyes disease, stomach pain, snake and scorpion bites and as antispasmodic, aphrodisiac and as emmenagogue agents
(Niroumand et al., 2018). In folk medicine, it has been commonly used for treating insufficiency of ovaries, uterine bleeding, premenstrual syndrome, fibroid cysts, infertility and acne of teenagers. It has also historically been used to promote digestion, sedation and anti-infection
(Arokiyaraj et al., 2009).
The fruits of Vitex are called Manjingzi in Chines Pharmacopoeia. Manjingzi is a Chines traditional medicine used to recover ophthalmodynia, migraines and headaches. The leaves of Vitex are used in treating asthma, phlegm and coughs
(Yao et al., 2016). Several parts of Vitex including seeds, roots and leaves are commonly used as anti-inflammatory, anti-rhumatism, analgesic and insecticide agents
(Zheng et al., 2015).
In Arabic countries, the dried seed is taken orally as a lactogenic agent and emmenagogue. The hot water extract is used as a contraceptive and the entire plant is inhaled, by fumigation, as an emmenagogue (
Razzack, 1980). In Morocco, the seed and leaf powder used externally or fumigation to treat burn, cold and headache (
Saadi et al., 2013).
Alternative and complementary medicine uses
Nowadays, VAC is widely used in USA in complementary and alternative medicines as a medicinal plant to treat premenstrual syndrome (PMS) (
Weis and Kaapen, 2009,
Niroumand et al., 2018). It has fewer side effects so it used as effective alternative herbal medicine to treat symptom related to PMS (
Röhrl et al., 2017). Fruits traditionally used to treat minor symptoms of PMS such as monthly pain, mood disorders and swelling (
Dickerson, 2003;
Röhrl et al., 2017). In Europe, the fruits extract used as effective alternative agent instead the chemical drugs to treat PSM
(Berger et al., 2000). The agency of European medicines and Health authorities in Germany have confirmed the positive effects of the VAC on menstrual cycle management and the PMS and Mastalgia care
(Girman et al., 2003 and
Mari et al., 2015). It well known in North America and in Europe as an effective substitute instead of the pharmaceutical drugs in treating other different disorders such digestive complaints, Acne, infertilities and lactation supports
(Niroumand et al., 2018).
Vitex has been included in numbers of herbal perpetrations which used in clinical treatment. Clinical evidence indicates that the extract of VAC dried fruits is effective for the recovery of premenstrual syndrome, menstrual abnormality, amenorrhea, mastidynia and hyperprolactinemia which all due to elevated the level of prolactin
(Azarnia et al., 2007). Both fluid extract or dried leaves extract in pill form were used in clinical trials at various doses
(Azarnia et al., 2007; Carmichael and Can, 2008;
Dugoua et al., 2008). A routine consumption of 30-40 mg of dried herb in capsules or liquid preparation is recommended by German commission E monograph. This is normally taken once in the morning sequentially with liquid for several months. For premenstrual syndrome or heavy period, the herb can be consumed for 4-6 months on a regular basis. Infertile women with amenorrhea can consume the
V. agnus castus for 12-18 months unless they are pregnant during treatment (
Healthnotes Resource, 2006).
Clinical application
Chaste tree has dopaminergic, estrogenic, cytotoxic and probably antibiotic properties. Clinical studies have shown that it can be used to cure galactorrhea, mastodynia, hyperprolactinemia and premenstrual syndrome. Sub-fertile women suffering from hormonal problems which resulted from hyperprolactinemia with consecutive luteal phase insufficiency, using chaste tree preparation can be very helpful (
Anwendung, 2009).
Female reproductive system hormonal disorders
The, development and the function of the female reproductive system depends upon hormone concentrations and balance. Endocrine dysfunctions may lead to many abnormalities
e.g., menstrual cycle irregularities impaired fertilities endometriosis and polycystic ovarian syndrome (PCOS). These abnormalities may results from modulation of the concentration of estrogens thecal androgens and thyroid hormones (
Nicolopoulou-Stamati and Pitsos, 2001). Irregular or absent menstrual periods due to ovulation problem which account for subfertility in 20-25% of couples It can be, substantiated through measurement of reproductive hormones
(Bretveld et al., 2006).
Vitex modulates the rise or reduction in sex hormones by physiological and pharmacological activities
(Liu et al., 2004). Studies by
Jelodar and Askari (2012) demonstrated that the vitex extract rise the progesterone concentration and reduce the testosterone concentration but Vitex doesn’t change the level of de-hydro-epi-androstenedione and estrogen in animal with polycystic ovary syndrome (PCOS).
Ibrahim et al., (2008) found that Vitex rises the level of progesterone and estrogen hormone and decrease the level of LH without affecting FSH hormone in ovariectomized rats.
Vitex secrets substantial amount of androgen that converted to estrogen
(Ibrahim et al., 2008). Apigenin is the main active phytoestrogen in vitex, can bind to the estrogen receptors
(Jarry et al., 2003). Linoleic acid which considered one of estrogenic substance in Vitex, can binding to estrogen receptors and stimulate certain estrogen inducible genes
(Liu et al., 2004). Vitex modulates the Luteal phase disorders in female and rises the progesterone level, thereby the chance of conception is improved
(Ahangapour et al., 2016). Lu et al., (2011) reported that Vitex probably elevates the progesterone concentration which leads to regulate luteal phase dysfunction.
Earlier research showed that VAC fruit extract controls the imbalance of sex hormone levels like progesterone hormone in PSM
(Milewicz et al., 1993). Xu et al., (2014) revealed that Vitex returned the regular function of the abnormal estrous cycle in D-galactose and aging group female mice, Vitex, also lightly rise the weight of ovaries and uterus and ovaries and uterus weight / body weight percentage in D-galactose and aging group mice.
Primary dysmenorrhea
Many women monthly suffer from menstrual cramps which sever enough to impact their quality life and work productivity
(Ju et al., 2014). In primary dysmenorrhea, a condition related to PMS, intense uterine contractions are thought to trigger moderate to intense pain and mediated by the release of prostaglandins, leukotrienes and infiltration of leukocytes that normally accompany the breakdown of endometrial lining (
Röhrl et al., 2017). Primary dysmenorrhea identified by hyper-production of uterine prostaglandins, especially PGF2a and PGF 2 resulting in increased uterine tone and high-amplitude contractions
(Iacovides et al., 2015; Bernardi et al., 2017). Prostaglandin production is controlled by progesterone and progestrone level drops immediately prior to menstruation and prostaglandin level increase
(Bernardi et al., 2017). It was found that Vitex extract modulate a number of potential mechanism responsible for dysmenorrhea. The studies on Vitex extract showed it is potent anti-inflammatory as it has ability to suppress leukotriene synthesis, cytokines release and reactive oxygen species (ROS) production from isolated leukocytes which prevent spasmodic action and support beneficial effects of extract (
Röhrl et al., 2017).
Menopausal symptoms
Menopause is transition natural period occurs in women life
(Norozi et al., 2010). Menopausal symptoms have significant undesirable effects on women quality life
(Naseri et al., 2019). During menopause the activities of estrogen and progesterone dramatically reduced
(Tanira et al., 2009). Taking VAC extract as a phytoestrogenic therapy can relieve menopausal symptoms in women
(Naseri et al., 2019). Conducting numerous alternative or complementary therapy to alleviate the unpleasant effects of menopause is commonly acceptable today. Amongst, phytoestrogens are conducted as hormonal remedies in menopausal women; which have less possible side effects due to their herbal source
(Jing et al., 2009).
Vitex agnus-castus has phytoestrogenic activities
(Ahangarpour et al., 2016) and used to cure irregular menstruation, menopausal complication and menstrual pain
(Naseri et al., 2019). The dopaminergic activities of VAC are documented in pharmacological research, intimacy to opioid receptors and capability to rise melatonin secretion support the Vitex activities to reduce the menopausal symptoms (
Van Die et al., 2009).
Furthermore
Vitex agnus-castus has antiaging, antioxidant effects with high level of phytoestrogen. It was established that the Vitex decreases many aging problems in female mice reproductive system. It can be useful for some aging events such as oxidative stress, deficiency women’s sex hormones and an atrophic endometrium
(Ahangarpour et al., 2016).
Adverse effects
The safety of VAC was studied and the adverse effects have been found to be mild and reversible (
Bornhorst, 1996;
dugoua et al., 2008; Ho Sh et al., 2011;
Rani and Sharma 2013;
Niroumand et al., 2018). The most common ones emphasize: Nausea, headache, mild gastrointestinal complaints, fatigue, Menorrhagia, dry mouth, acne, pruritus and erythematous rash (
Rani and Sharma 2013;
Daniele et al., 2005).
Randomized controlled trials conducted in a woman with PSM, luteal phase defects or premenstrual dysphoric disorder. Some of these studies did not mention any adverse effects and showed few adverse effects which included acne, multiple abscesses, inter-menstrual bleeding, urticarial and each event was reported once only and resolved without discontinuation. Non-randomized clinical trials conducted in women and men treated with VAC at least for 3 months, no mention of adverse events was made
(Claudia et al., 2005).
