VERBENACEAE

The Verbenaceae consists of herbs, shrubs or trees, with square stems and opposite or rarely alternate leaves. The flowers are similar to those of the Lamiaceae except that the ovary is entire, with the style proceeding from the top, and the flowers are in racemes or cymes rather than in verticils. The fruit is dry or succulent usually shorter than the persistent calyx, 2- or 4-celled with one seed in each cell.

Vitex agnus-castus and Verbena officinalis are medicinal plants of the Verbenaceae.

Verbena officinalis

Vervain

Family Verbenaceae

Description

An annual or short-lived erect perennial, nearly glabrous, with square stemmed, spreading, wiry branches which may grow to 80 cm tall. Basal leaves stalked, obovate or oblong, dark green and deeply toothed, upper leaves opposite, few, often sessile and lanceolate. Flowers very small, pale blue, in long, slender spikes, the lower ones becoming distant as the spike lengthens, each one sessile in the axil of a small bract. Flowers from summer to autumn.

Habitat and cultivation

Native to Europe, North Africa and West Asia, in damp, sunny situations and widely naturalised. Grows from seed and is better shown fresh each year. Old plants become straggly and less productive. Drought tender, frost resistant.

Parts used

The herb gathered at, or just prior to, flowering. In Germany the roots are also used.1

Active constituents

1) Iridoids—mainly verbenalin (cornin) around 0.1–0.3% highest during flowering and in mature plants.^2–7 Also hastatoside and aucubin

2) Phenylpropanoids (up to 5%) including verbascoside and its isomer eukovoside and their derivatives2,5,6

3) Flavonoids including those based on luteolin, apigenin, kaempferol, quercetin, diosmetin and wogonin^2,3,5,6,8,9

4) Volatile oil including citral, limolene, cineol and β-myrcene¹⁰

Also contains mucilage, tannins, sterols including daucosterol¹¹ and β-sitosterol,¹² triterpenes including ursolic and oleanolic acids^13,14 and fatty acids.¹⁵

Nutritional constituents

Vitamins: C¹⁶ and β-carotene¹⁷

Minerals: Rich in minerals especially calcium and magnesium, also sodium, potassium, iron, copper, zinc and manganese¹⁸

Actions

1) Nervine

2) Thymoleptic

3) Diaphoretic

4) Sedative

5) Spasmolytic

Also reputedly a galactagogue.

Scientific information

Verbena is a medicinal herb that enjoyed a great reputation in the past, being used for a wide range of health conditions.¹⁹ Although the active constituents have been investigated in recent times the pharmacological activity has not and the herb appears to have lost some of its former esteem.

Verbena has been part of the medical tradition of both the East and the West. In Spain the herb has been used as a topical anti-inflammatory,²⁰ in Sicily as a treatment for psoriasis,²¹ in Morocco for hypertension²² and in China for malaria.

In vitro—Studies that have been conducted indicate:-

• the essential oil has good anti-oxidant activity²³
• the herb can moderately inhibit COX-1 activity.²⁴ (Animal studies indicate the herb and/or isolated constituents have anti-inflammatory activity^12,20 and that the herb has potential as a neuroprotective agent for example against Alzheimer's disease.²⁵)
• the flavonoids have antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli²⁶
• the herb has strong oestrogen and progesterone-receptor binding capacity²⁷ (an early study had shown it to be androgenic¹)
• citral, at concentrations equivalent to that found in infusions, is apoptotic in several haemopoietic cancer cell lines²⁸

In vivo—An epidemiological study found that drinking herbal teas, Verbena being one commonly consumed, was inversely related to the incidence of breast cancer possibly due to the polyphenol (flavonoids and phenylpropanoids) and/or essential oil content.²⁹

Medicinal uses

Cardiovascular system

• fevers (in early stages)
• colds
• influenza

Gastro-intestinal tract

• cholecystalgia
• jaundice

Nervous system

• depression
• melancholia
• epilepsy
• migraine
• hysteria
• convalescence

Reproductive tract

• increase lactation

Pharmacy

Three times daily
Infusion	–   2–4 g
Tincture 1:5 (40%)	–   5–10 ml
Fluid Extract (25%)	–   2–4 ml

Precautions and/or safety

Verbena infusions inhibited iron absorption in an in vitro model30 and an in vivo test with a single food source has estimated inhibition of iron up-take to be around 59%.³¹ Iron absorption is inhibited by polyphenols but the effect is less than occurs with black tea. The actual inhibition may be altered when taken with complex meals, as occurs in real life.

There is a report of contact dermatitis to the herb.³²

Historical uses

Abscesses; tumours; sores/wounds—styptic and vulnerary; as an antidote to poisons, haemorrhoids; facial neuralgia; calculus; “cold complaints of the womb”, infertility; aphrodisiac; headaches (poultice); rheumatism (external); worms; the plague; mouth ulcers, acute dysentery, enteritis. As a wash for freckles and morphews; to clear eyesight and strengthen it.

Vitex agnus-castus

Chaste tree, agnus-castus

Family Verabenaceae

Description

An aromatic, deciduous shrub or small tree, growing 1–4 × 2 m high with branches that divide frequently at the top. Branches are felted with dense white hairs. Leaves are long-stalked, palmate with 5–7 lance-shaped leaflets, green above and felted beneath. Flowers grow in long, terminal, interrupted spikes and are small and usually lavender coloured, rarely rose-pink. Corolla 6–9 mm, almost two-lipped, hairy outside. Stamens longer and projecting. Calyx hairy. Fruits fleshy and reddish black. Flowers mid to late summer.

Habitat and cultivation

Native to Southern Europe and Western Asia growing in moist, well-drained soil in sheltered, sunny places. Grown from stratified seed or cuttings. Frost resistant, drought tender.

Parts used

The berries harvested when ripe in autumn.

Active constituents

1) Iridoid glycosides including agnuside, aucubin and eurostoside³³

2) Flavonoids—mainly the tetramethoxyflavone, casticin, also orientin, eupatorin, apigenin, luteolin and penduletin^34–36

3) Essential oil

a) monoterpenes—sabinene, 1,8-cineole, β-caryophyllene and farnesene³⁷

b) diterpenes including those of labdane type—vitexlactam, rotundifuran, vitetrifolin B, C and D—and clerodane type^38–41

c) sesquiterpenes—spathulenol³⁵

Also contains fatty acids including linoleic acid.⁴²

Nutritional constituents

Vitamins: C and carotene

Actions

1) Hormone regulator

2) Galactagogue

Vitex has been documented as having emmenagogue, vulnerary, carminative, anthelmintic and anti-inflammatory properties but scientific corroboration of these is lacking.

Scientific information

Various parts of chaste tree have been used medicinally for thousands of years. The fruits in particular, besides being used as a food spice by the monks (hence the name monk's pepper), were believed to ensure celibacy and chastity which would have been an added advantage to them. Unlike Verbena the reputation of this herb seems to have grown in recent times making it one of the most commonly used herbs employed for hormonal imbalance. Its primary use today, for menstrual disorders, was however known from ancient Greek times.⁴³

There have been a number of studies into its action over the last fifty years and clinical efficacy has resulted in German Commission E approving the herb for premenstrual syndrome (PMS), mastalgia and irregular menstruation.

Hormonal

In vitro—The chemistry and pharmacology of Vitex is complex but mechanisms thought to contribute to its action include:-

• interaction at dopamine D₂-receptors in the anterior pituitary gland which reduces prolactin levels, is due at least in part to the diterpenes, and is presumed to be the mechanism by which the herb helps with breast discomfort, referred to as mastalgia or mastodynia.38,44,45 Dopamine agonists have been found empirically to reduce breast pain and heaviness and mood disturbances associated with PMS. (Prolactin is elevated in 70% of women who suffer breast discomfort premenstrually⁵⁰)
• interaction with oestrogen receptor (ER) sites⁴⁶—the action appears complex. The whole extract had no binding affinity for ERα⁴⁷ although its constituent linoleic acid bound to both ERα and ERβ sites.⁴² On the other hand the flavonoids, apigenin and penduletin, have affinity for ERβ receptors—these receptors are involved in fat tissue regulation, prevention of malignant proliferation and may counter ERα activity^38,48
• may interact at cholinergic receptor sites⁴⁹
• interaction/agonist activity at µ-opiate and possibly other opiate receptor sites.⁴⁵ The µ-opiate receptor is mainly activated by β-endorphin, an endogenous peptide, which helps regulate the menstrual cycle via the hypothalamic- pituitary-adrenal (HPA) axis. The opiate system is also involved in pain perception, mood and appetite regulation and the level of β-endorphin is inversely proportional to the severity of PMS symptoms like abdominal discomfort, anxiety and food cravings.⁴⁹

In vivo–At least 30% of women are considered to experience pre-menstrual problems and according to one set of criteria for about 2.5–3.0% of all women of reproductive age symptoms are severe whilst in 40% they are moderate. The aetiology of PMS symptoms is proposed to be due to one or several of the following factors⁵⁰:-

• low progesterone levels in the luteal phase
• disturbance of aldosterone activity (fluid retention)
• imbalance in HPA axis activity with reduced adrenal hormones
• disturbances in neurotransmitters
• prostaglandin deficiency
• raised levels of prolactin
• nutritional factors e.g. low calcium and magnesium levels, vitamin deficiencies, food intolerance
• stress

Clinical trials into the effects of Vitex for hormonally-related problems have so far shown benefit for:-

• moderate to severe PMS⁵¹
• the majority of symptoms associated with PMS including psychological (anger, irritability, mood alteration, negative feelings) and physical (bloating, headache, breast fullness, pain, fluid retention)^52–55
• PMDD—Premenstrual dysphoric disorder—effects comparable to fluoxetine, the SSRI being specifically better for psychological symptoms and Vitex for physical ones⁵⁶
• cyclical mastalgia^54,57,58—prolactin level reduction comparable to bromocriptine
• luteal phase defects due to latent hyperprolactinaemia—it reduced prolactin level, normalised length of the luteal phase and progesterone production57,59
• pathologically raised prolactin levels⁵⁷
• infertility—due to secondary amenorrhoea or luteal insufficiency⁶⁰—Vitex raised progesterone levels, lengthened duration of raised basal temperature in the luteal-phase and normalised the length of both long and short cycles⁶¹
• menopausal hot flushes and night sweats—Vitex was one herb in a combination. There were no adverse changes to hormone levels, vaginal tissues or liver function⁶²

A number of clinical trials conducted some decades ago reported that Vitex benefited acne vulgaris,^63,64 premenstrual fluid retention,⁶⁵ amenorrhoea⁶⁶ and increased lactation.⁶⁷ There are also anecdotal reports of the herb reducing prolactin levels caused by pituitary micro-adenomas.^68,69

Based on measurements in healthy men it seems that the dose of Vitex used can vary the response of prolactin secretion (biphasic)—levels were increased slightly at low doses of Vitex but decreased slightly at higher doses.⁷⁰ Furthemore these changes were larger the higher the base level of prolactin prior to dosing.⁷⁰

Other

In vitro—Both water and ethanol extracts of Vitex are significantly anti-oxidant, the flavonoids were not considered to be wholly responsible for this activity.^35,71

Extracts have antitumour and antiproliferative activity in a number of fast growing or cancer cell lines including gastric,⁷² prostate,⁷³ breast,⁷⁴ ovary,⁷⁵ colon⁷⁵ and lung.⁷⁵ This action does not seem to be specific for cancer cells however,⁷⁵ affecting other relatively fast growing cell lines and indicating a potential use of the herb in the treatment of benign prostatic hyperplasia.⁷³

In vivo—Melatonin levels were increased in healthy men in a dose-dependent manner by Vitex although the actual circadian rhythm of secretion was unaffected.⁷⁶

Sprays made from the berries had good insecticide properties against fleas, mosquitoes, flies and ticks.⁷⁷

Medicinal uses

Reproductive tract

Vitex is used almost exclusively in women as a hormone balancer for:

• amenorrhoea, secondary
• metrorrhagia
• oligomenorrhoea
• infertility
• menopausal symptoms
• menorrhagia
• polymenorrhoea
• cyclical mastalgia
• premenstrual syndrome
• to help regulate menstrual cycle on cessation of contraceptive pill

Its indications include any condition that subsided in pregnancy and returned at the cessation of breast feeding or any premenstrual aggravation.

Skin

• acne (70% improvement in 3 months)

This effect may be due to an anti-androgenic action. It is useful for teenage acne in both sexes.

Pharmacy

Three times daily
Decoction	–   0.2–2 g

The daily dose that follows may be effectively taken as a single dose before breakfast.

Tincture 1:5 (25%)–1–3 ml (20–60 drops).

Alternatively the weekly dose may be given in equal doses, three times a day.

Vitex used in the above trials were standardised on casticin and represented the equivalent of 120–480 mg of herb daily.

The study on prolactin changes in men used a low dose of 120 mg and high dose of 480 mg.

Precautions and/or safety

All the above clinical trials report good tolerance to the herb. Although most trials on PMS measured improvements after 3 cycles, these can be expected to occur sooner than that. In the one study that used a 3 cycle treatment protocol with follow-up carried out 3 cycles after cessation of Vitex, symptoms had returned to around 22% below where they were before Vitex was used.53

In spite of the herb's ability to reduce prolactin levels it is not contra-indicated in lactation and in fact studies have supported its use for improving milk flow, a process governed by prolactin. The biphasic response to Vitex may explain this anomaly or it may be due to mechanism(s) not yet understood.

Side-effects that have been reported include nausea, headache, itching, erythema, gastro-intestinal disturbances, depression, fatigue, breast pain, menstrual disorders and acne.^51,78 They are however infrequent, mild and reversible. Large doses should be avoided although no toxicity due to overdose has been reported.

There is one report of mild ovarian hyperstimulation syndrome attributed to the use of Vitex in a woman undergoing unstimulated in-vitro fertilisation treatment⁷⁹ and one of arteriospasm.⁷⁸

Interactions

No interactions have been reported in the extensive testing that has been done to-date although a theoretical interaction has been suggested between Vitex and dopaminergic antagonists.⁷⁸

Some of the clinical trials on PMS included women using contraceptive pills (unspecified type) as the latter do not always improve these symptoms. No interactions have been reported from using the two concomitantly.^52,53

Historical uses

To curb sexual desire; inflammation, injuries; animal bites, an enlarged spleen; inflamed uterus. Paralysis; pains in the limbs; weakness.