Fructus Agni Casti consists of the dried, ripe fruits of Vitex agnus-castus L. (Lamiaceae)
A small tree or deciduous shrub, approximately 1–6 m in height, with aromatic odour. Leaves: opposite, long-petiolate, palmately-compound with 3–9 stipulate leaﬂets; leaﬂet blade linear-lanceolate, apex and base acuminate, 1.5–10.0 cm long, 0.5–2.0 cm wide; the central leaﬂet is the longest, dark green and glabrous above, velvety white-tomentose below; margin entire to sparsely toothed. Inﬂorescence: terminal panicle, 12.0–17.5 cm long, and composed of many sessile-subsessile cymes. Flower: perfect, campanulate symmetric, white-tomentose; calyx 5-toothed, campanulate, 2.0–2.5 cm long; corolla blue, pink, yellowish or white, salverform, tube 6–7 mm long, limb 2-lipped, upper lip 2-lobed, lower lip 3-lobed; stamens 4, exerted, 2 long, 2 short, inserted near top of corolla tube, alternate with corolla lobes; ovary superior, style exerted, stigma biﬁd. Fruit: drupe, globose to subglobose, 2–4 mm in diameter, reddish.
Synonyms: Agnus-castus vulgaris Carr., Vitex verticillata Lam
Selected vernacular names
Abraham’s balm, Abrahamsstrauch, agneau-chaste, agnocasto, agnos-casto cumune, agnus-castus, angarf, ârbol casto, ârbolde la castidad, arbre au poivre, athlak, banjankusht, barátcserje, bish barmagh aghaji, chaste tree, chasteberry, common chaste tree, daribrahim, felfele barry, fanfangosht, gatileira comum, gattilier, gattilier commun, hab an nasl, hab el fakd, hab a khouraf, hayit, hemp tree, jurema, kaff maryam, kef-meriem, kerwa, Keuschbaum, Keuschlamm, kyskhedstrae, lilac chastetree, lygos, Mönchspfeffer, Mönchspfeller, monk’s pepper, monk’s pepper tree, Müllen, non’s peppertree, panj angosht, panjangusht, pape falso, peperella, petite poivre, pimiento menor, poivre de moine, poivre sauvage, ranukabija mah, sagetree, sauzgatillo, seiyo-ninzin-boku, shajerat Ebrahim, shagareh Ibrahim, sinduvara, tree of chastity, true chaste tree, vitex, vitiu, wild lavender, Yemen safrani.
Native to the Mediterranean region and Asia. Cultivated in warm temperate regions of the world, and obtained primarily from Mediterranean countries, especially Albania and Morocco.
Major chemical constituents
Up to 2.0% essential oil with bornyl acetate, 1, 8-cineol, limonene, A-pinene and B-pinene being primary constituents. Flavonoids, iridoids and diterpenes represent major groups of secondary constituents found in the fruit. Casticin, in concentrations up to 0.2% (12) is considered the major ﬂavonoid, with chrysosplenetin, chrysosplenol D, cynaroside, 5-hydroxy3, 4´, 6, 7-tetramethoxyﬂavone, 6-hydroxykaempferol, isorhamnetin, luteolin and luteolin 6-C-glycoside (isoorientin) derivatives being other compounds of this class. Diterpene constituents include vitexilactone (0.001–0.004%), 6B, 7B-diacetoxy-13-hydroxylabda-8, 14-diene, rotundifuran, and vitexlactam A.
Medicinal uses of Fructus Agni Casti
Uses supported by clinical data
Orally for the symptomatic treatment of gynaecological disorders including corpus luteum insufﬁciency and hyperprolactinaemia, premenstrual syndrome, menstrual irregularities, cyclic mastalgia and also to treat hormonally-induced acne
Uses described in pharmacopoeias and well established documents
Orally for the treatment of endometrial hyperplasia and secondary amenorrhoea; endocrine-dependent dermatoses (dermatitis symmetrica dysmenorrhoica (Matzenauer-Polland syndrome)) acne vulgaris, eczema, acne rosacea), hypermenorrhoea, infertility due to hyperprolactinaemia and luteal phase defect. Used to treat ﬁbroid cysts and infertility, to stop miscarriages due to progesterone insufﬁciency, to help expel the placenta after birth and also as a digestive aid, sedative, anti-infective and for the treatment of hot ﬂushes.
Effect on prolactin secretion
An ethanol extract of the fruit (1:10 with ethanol, 62%), in a range of concentrations from 0.41 to 3.3 mg/ml, signiﬁcantly inhibited basal and thyroid stimulating hormone-stimulated prolactin secretion from rat primary pituitary cell cultures in vitro (p < 0.05). At a concentration of 3.3 mg/ml the inhibition was 80% for basal secretion and 65% for stimulated secretion. These results were conﬁrmed in another study demonstrating signiﬁcant inhibition of prolactin release from rat pituitary cells by the extract at concentrations of 0.5mg/ml for basal secretion and 0.125mg/ml for stimulated secretions.
Furthermore, inhibition of prolactin secretion from rat pituitary cells was also observed after treatment with an extract of the fruit at concentrations of 460 μg/ml (p < 0.0003) for basal secretion and 115 μg/ml for stimulated secretion (p < 0.01). The inhibitory effect of a fruit extract on prolactin secretion was investigated in male rats. Intravenous administration of a 53% ethanol fruit extract containing 20 mg/ml of water-soluble constituents signiﬁcantly inhibited stress induced prolactin secretion as compared with the baseline (p < 0.05)
The median lethal dose of an ethanol extract of the fruit after a single intragastric or intraperitoneal injection was greater than 2.0 g/kg body weight (bw) in rats and mice, and no deaths were reported. In a 28-day sub-acute toxicity study the no-observed-effect level was 50.0 mg/kg bw; chronic administration over 26 weeks resulted in a no observed-effect level of 40.0 mg/kg bw. No genotoxic effects were observed when the same extract was tested in the thymidine kinase mutation assay in mammalian cell lines, the unscheduled DNA repair assay in rat hepatocytes or in the micronucleus assay of murine bone marrow cells
Two uncontrolled clinical studies and one observational report have assessed the effects of extracts of the fruit on acne due to hormone imbalance. In one open study, 118 people with acne were treated with a fruit extract (20 drops twice daily for 4–6 weeks, then 15 drops twice daily for 1–2 years) and the results were compared with those of conventional treatments for acne. Patients treated with the fruit extract reported a quicker healing rate after 6 weeks and after 3 months of therapy, 70% of patients treated with the fruit extract had complete healing.
Abnormal menstrual cycles and infertility
Since 1954 at least 17 studies have assessed the effects of extracts of the fruit on a variety of menstrual cycle disorders including amenorrhoea, oligomenorrhoea, polymenorrhoea, corpus luteum insufﬁciency and infertility. Two double-blind placebo-controlled clinical trials and several observational studies have investigated the effect of various extracts of the fruit on corpus luteal phase dysfunction and infertility. The products tested were all ethanol extracts (53–70% ethanol), and the doses used in these investigations were: 20 drops twice daily; 15 drops three times daily; 30 drops twice daily; or one to two tablets or capsules daily.
A randomized, double-blind, placebo-controlled trial involving 52 women with luteal phase defects due to latent hyperprolactinaemia assessed the efﬁcacy of a dried fruit extract (19). The aim of the study was to ﬁnd out whether elevated pituitary prolactin levels could be reduced and if deﬁcits in luteal phase length and luteal phase progesterone synthesis could be normalized.
Latent hyperprolactinaemia was analysed by monitoring the prolactin release 15 and 30 min after intravenous administration of 200 Mg of thyroid hormone. Thirty-seven cases (placebo: n = 20; treatment: n = 17) were included in the ﬁnal statistical analysis. After 3 months of treatment with the extract at a dose of 20 mg per day, prolactin release was reduced; a signiﬁcant increase in the length of the luteal phase (10.5 days; p < 0.05) was observed. Deﬁcits in luteal progesterone synthesis were eliminated. These changes only occurred in women in the treatment group, no change was observed in the placebo group.
All other hormonal parameters remained unchanged, except for 17-B-estradiol, which increased during the luteal phase in women in the treatment group. The overall length of the menstrual cycle did not change, suggesting that there was a corresponding shortening of the follicular phase. Two women in the group given the extract had become pregnant by the end of the study. No side-effects were reported.
Two larger post-marketing trials, involving 479 women, assessed the safety and efﬁcacy of fruit extracts for the treatment of oligomenorrhoea or polymenorrhoea. The women were treated with 30 drops of the extract twice daily and the outcome measured was the bleeding-free interval. An increase in the bleeding-free interval was observed after 35 days in 187/287 women receiving treatment for oligomenorrhoea and after 26 days in 139/192 women receiving treatment for polymenorrhoea.
Effects on lactation
Only one randomized, double-blind controlled trial examined the effect of the fruit in lactating women. Women were treated with the fruit extract (15 drops three times daily) or vitamin B1 (no dose stated) or assigned to the control group (details not stated). Lactation in all groups increased up to day 10 postpartum; from days 10–20 a decrease in lactation was observed in women in the control and vitamin B1-treated groups. Lactation in women in the group treated with the fruit extract increased or was maintained up to day 20. Lactating women with poor milk production treated with a fruit extract were able to effectively increase production. No statistical analyses were performed.
Adverse reactions have been reported in some clinical trials. A review of 30 studies involving 11506 subjects reported a total of 246 adverse events, thus representing an adverse reaction rate of approximately 2%. The major reactions reported included acne, changes to the menstrual cycle, dizziness, gastrointestinal distress, increased menstrual ﬂow, nausea, skin reactions, urticaria and weight gain. Minor adverse events include fatigue, hair loss, increased intraocular pressure, palpitations, polyurea, sweating and vaginitis.
Patients reporting a feeling of tension and swelling of the breasts or menstrual disturbances should consult a health care provider for a medical diagnosis
Although no interactions have been documented, the reported dopaminergic effect may reduce the efﬁcacy of dopamine-receptor antagonists. Furthermore, due to its potential hormonal effects, Fructus Agni Casti may interfere with the effectiveness of oral contraceptives and hormone replacement therapy.
Carcinogenesis, mutagenesis, impairment of fertility
Intragastric administration of an ethanol fruit extract to male and female rats at doses up to 80 times the recommended human daily dose had no effect on fertility, mating behaviour, pregnancy or lactation. No pathological changes were observed in any of the offspring of treated animals when compared with those animals treated with vehicle control
Pregnancy: teratogenic effects
Intragastric administration of an ethanol fruit extract to rats and rabbits at doses up to 100 and 74 times higher than the human daily dose, respectively, was not teratogenic and did not affect maternal health as compared with controls
One study in rats assessed the effect of a fruit extract administered orally to lactating dams on their offspring. A decrease in milk consumption in the offspring was observed and a high rate of mortality resulted compared with untreated animals. Normal milk consumption patterns were resumed in the offspring when the dams were no longer given the extract. No further data are available; therefore the use of the crude drug by nursing mothers is not recommended.
No safety data are available, therefore the use of the crude drug in children under the age of 12 years is not recommended.
Posology (Unless otherwise indicated)
Dry native extract: 8.3–12.5:1 (w/w), approximately 1.0% casticin: 1 tablet containing 2.6–4.2mg native extract, swallowed whole with some liquid each morning.
Dry native extract: 9.58–11.5:1 (w/w): 1 tablet containing 3.5–4.2 mg native extract each morning with some liquid.
Dry native extract: 6.0–12.0:1 (w/w), approximately 0.6% casticin. For premenstrual syndrome: 1 tablet containing 20 mg native extract daily with water.
Fluidextract: 1:1 (g/ml), 70% alcohol (v/v): 0.5–1.0 ml.
Tincture: ethanol 58% (100 g of aqueous-alcoholic solution contains 9 g of 1:5 tincture): 40 drops, once daily with some liquid each morning.
Tincture: ethanol 53% (10g of the solution contains 2g crude drug mother tincture): 30 drops twice daily.
Tablet: containing 162 mg of crude drug mother tincture (1:10 with 62% ethanol), twice daily.
Hydroalcoholic extracts (50–70% v/v): corresponding to 30–40 mg dried fruit
WHO monographs on selected medicinal plants; Volume 4, 2009
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