FABACEAE

Fabaceae—the pea family, formerly Leguminosae. This is the third largest plant family in the world with over 650 genera. The Fabaceae is a cosmopolitan family of trees, shrubs, lianes, water plants and herbaceous plants and most have root nodules containing nitrogen-fixing bacteria which make atmospheric nitrogen available to the plant.

Economically the Fabaceae family is important because many genera produce edible seeds e.g. peanuts, carob, chick peas, soya beans, lentils, peas and beans. Melilot, clovers and lucerne are important fodder crops.

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Characteristics

Fabaceae is sometimes treated as 3 families: Caesalpinioideae, Mimosoideae, and Papilionoideae.

Baptisia tinctoria

Wild indigo

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Family Fabaceae

Description

A slender, glaucous, bushy-branching perennial herb which grows 30–60 cm tall. Root large, irregular, ligneous, light yellowish-brown inside, black externally. Numerous rootlets. Leaves trifoliate, mostly sessile, dark blue-green with a light green stripe on the midrib, leaflets rounded or cuneate-obovate. Stem smooth, glabrous, round, branching. Inflorescence short, loose, few-flowered in terminal racemes. Flowers canary yellow, about as long as leaflets, calyx cup-shaped. Fruit an oval, centrally inflated legume stalked in the persistent cup of the calyx. Seeds many, ovoid and cinnamon brown.

Habitat and cultivation

Indigenous to Canada and USA in open, sunny areas of well-drained sandy soils. Grows in some other countries. Grown from seed sown in winter/spring. Frost resistant, drought tender.

Parts used

The roots gathered in the spring or autumn of the second year onwards. The fresh root was preferred by the Eclectics.

Active constituents

1) Alkaloids including cytisine1 (probably identical to baptitoxin)2

2) Polysaccharides including arabinogalactan-proteins (glycoproteins)3 and heteroglycans4

3) Flavonoids including isoflavones (genistein)

4) Oleo-resin

5) Coumarins

Actions

1) Antimicrobial

2) Immunostimulant

3) Laxative

4) Antipyretic

5) Mild cardioactive

Scientific information

Baptisia was a valued medicine for indigenous North Americans. It was introduced to European settlers in the late 18th Century and they found it effective for treating infectious diseases. In recent times it has suffered from over-harvesting.

In vitro—The arabinogalactan-proteins in Baptisia may have similar physiological properties, but are not structurally the same, as those found in Echinacea spp.5

The water-soluble polysaccharide or heteroglycan fraction is immunostimulating.4,6

In vivo—Recent studies have mainly been carried out on Baptisia, in combination with other herbs, to treat upper respiratory infections. They were significantly better than placebo in reducing these infections.7–9 The mode of action is likely to be antiviral as well as stimulation of non-specific immune function (increased macrophage activity)9,10 and/or immuno-balancing.8

Isoflavones are oestrogenic.

Medicinal uses

Cardiovascular system

Respiratory tract

The specific application of Baptisia is for infections in the upper respiratory tract:

Gastro-intestinal tract

Skin

Externally

Pharmacy

Three times daily  
Decoction –   0.3–1 g
Tincture BPC (1934) –   2–5 ml
Fluid Extract (60%) –   0.3–1.3 ml

The recommended ratio in the BHP for the ointment is 1 part fluid extract to 8 parts of base.

To date Baptisia has been found to be non-toxic,7,9 although cytisine itself, being similar to nicotine, is toxic.1

Historical uses

Liver problems, venereal disease, pains of varied nature, sepsis, intermittent fevers including typhus and scarlatina.

Cassia acutifolia and Cassia angustifolia [Formerly listed as Cassia senna]

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Alexandrian senna (C. acutifolia)

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Family Fabaceae Tinnevelly senna (C. angustifolia)

Description

C. acutifolia is a small shrub to about 60 cm high. The stems are erect, smooth and pale green, with long spreading branches with leaflets arranged in 4–5 pairs. They have an asymetric base and a thin stiff, brittle, light green lamina, often marked with transverse/oblique lines. They have a faint peculiar odour and a mucilaginous, sweetish taste (Grieve). Flowers are small and yellow and fruit is a pod 5 cm × 20–25 mm containing 5–7 seeds. C. angustifolia is an annual growing in the Middle East and India. It differs from C. acutifolia in the pod size which is 5 cm × 15–18 mm containing 7–10 seeds. These pods taste more bitter and harsh.

Odour—characteristic; taste—mucilaginous then slightly bitter.11

Habitat

Alexandrian senna is native to Egypt, Sudan and Nigeria. Tinnevelly senna is cultivated in India.

Parts used

The leaves and the fruit pods.

Active constituents11

1) Hydroxyanthracene glycosides (min. 3%) mainly the dianthrones—sennosides A (41%) and B (44%),12 also C and D13,14,† and small amounts of free anthroquinones rhein, aloe-emodin and crysophanol. Also rhein and C. angustifolia 1.2–2.5% hydroxyanthracene glycosides (calculated as sennoside B) whilst leaf content for both is a minimum of 2.5%. 8-glucosides,15 aloe-emodin glucosides,16–18 tinnevellin 8-glucoside (C. angustifolia)19 and 6-hydroxymusicin glucoside (C. acutifolia)20

2) Naphthalene glycosides

3) Flavonoids including kaempferol

4) Mucilage consisting of water soluble acidic polysaccharides21

Also contains pinitol, sugars and a gum isolated from the seeds containing galactomannans.22

The powder, on storage, may degrade to sennidin glucosides and sennosides oxidise at high temperatures to rhein 8-O-glucoside.23

Nutritional constituents

Minerals: Low levels of calcium, copper, magnesium, manganese and zinc24

Actions

1) Laxative

Scientific information

Senna was introduced to the west by the Arabs in the 9th Century although its recorded use dates back as far as 1550 BC.25 It has been a recognised medicine ever since and is still an official medicine in modern allopathic medicine, used to treat constipation.1 As a result its constituents are relatively well studied. The trend in laxative use is apparently declining. It had been a regular self-administered treatment, persisting more in the older age groups.26 Senna is however still one of the more popular over-the-counter products for constipation27 and it is used in hospitals.

Laxative

Sennosides A and B are considered the main active constituents.15 The strength of cathartic activity within this species is directly related to the level of sennosides.28 They pass to the large colon intact where gut flora metabolise them to produce active rhein anthrone which on absorption into the lumen wall stimulates the colon, through nerve and the immune cell stimulation, causing evacuation.29–31 Sennoside administration has been shown to increase peristalsis or propulsive activity in the ascending and descending colon, thereby reducing bowel transit time,32–35 and to increase the calibre of the lumen of all parts of the colon.36 By reducing transit time fluid re-absorption is reduced but there is also an increase in secretion of fluid into the colon, thus making stools more “fluid”.

In vivo—Many clinical trials have been conducted using pharmaceutical senna preparations with standardised sennoside levels, to stimulate bowel function. They were found effective:-

In prescribed doses sennosides do not disrupt the normal pattern of bowel emptying,11 alter gastric emptying or small intestine transit time.52 Senna's effect on bowel function does not persist on cessation of its use.53,54

A combination of senna and psyllium has been very effective in treating constipation,55 improving bowel function more than either agent alone.56

Other

In vitro—Cassia angustifolia has:

In Asian countries Cassia has been used traditionally as a topical agent to treat inflammation and in vitro studies have lent some support to this use.60

In vivo—Serum oestrogen levels in pre-menopausal women fell when senna was used throughout the cycle as the opportunity for hormone re-absorption from the colon was reduced.61 However the decreased transit time did not alter oxidative status or the level of plasma cholesterol or triglycerides.62

Medicinal uses

Gastro-intestinal tract

Pharmacy

Once daily  
Infusion  
Dried pods –   3–6 (C. acutifolia)
  –   4–12 (C. angustifolia-steeped in 150 ml of warm water for 6–12 hours)
Dried leaf –   0.5–2 g in a cup of water
Fluid Extract:  
Pods BPC (1973) –   0.5–2 ml
Leaves (25%) –   0.5–2 ml

The herb takes 8 to 14 hours to act and is best taken at bedtime or perhaps as a split dose, one at bedtime and the other in the morning.

It has been suggested that a hot infusion should be used to minimise possible microbial contamination.63

CONTRAINDICATIONS—Intestinal obstructions, inflammatory bowel disease, appendicitis, abdominal pain of unknown origin.

Pharmacokinetics

Rhein anthrone is taken up in small amounts from the colon and is metabolised to glucuronide and sulphate derivatives which can be found in urine and bile.31 The serum half life of rhein anthrone is between 4 and 12 hours31 and it is detectable in urine for 24 hours.64 Plasma levels of rhein show two peaks, one after 3–5 hours, presumed to be free rhein and the other after 10–11 hours relating to the bacterial release of rhein from the sennosides, aloe-emodin is below detection level.65

Precautions and/or safety

Clinical trials have reported the herb is safe when used at recommended doses.48,66,67 Used in preparation for colonoscopy in patients with ulcerative colitis it did not cause relapse from the remission phase of the disease.68

Senna in all its forms is not genotoxic, in vitro69 in particular the anthraquinone glycosides appear to be safe.70 In vivo assessment supports this finding too at prescribed doses.71

These preparations have also been declared safe for use in pregnancy and lactation,72–74 although German Commission E contraindicates such use.

The herb can cause griping and should therefore be administered with a carminative. Clinical studies comparing various laxatives have found that senna tends to be associated with more side-effects.75–77 It should not be used for longer than 10 days at a time. Overdosing can lead to fluid and electrolyte loss through diarrhoea and chronic use may lead to dependence and the need for higher doses.11

Because of the decreased colon transit time senna reduces the potential to absorb deoxycholic acid, the increased levels of which have been associated with cholesterol saturation of bile and gall stone development.78

There are a number of anecdotal reports of problems caused through the overuse/abuse of Cassia. These include reversible acute hepatic failure with renal impairment,79 hepatitis,80,81 hypogammaglobulinaemia,82 finger-clubbing83 and hypertrophic osteoarthropathy.84 In children under 6 years of age Cassia intake has resulted in severe nappy rash, blistering and skin sloughing.85

Rhein increases apoptosis of colon cells in vitro and stimulates leucocyte activity.86 In vivo a highly purified extract of sennosides affected the cell growth of the colon epithelium quite dramatically when administered as a once only enema causing widespread apoptosis and consequent replacement by cell proliferation.87 There is concern that chronic use of Cassia can lead to cancer and this may be a possible mechanism. Chronic use has certainly been linked to the development of pseudomelanosis coli. This is due to the deposition of a greater number of apoptic bodies in the colon mucosa that contain a melanin-like pigment derived from the anthroquinones and/or cell death.88 It has been suggested this condition may lead to bowel inflammation and possibly bowel cancer although no link has been found to date11 and there are no epidemiologic data actually linking senna use to increased colon cancer.89 Furthermore there was no evidence of inflammation or increased incidence of cancer even when used by people at high-risk for developing colorectal cancer.90,91 At present pseudomelanosis coli is considered harmless and reversible.11,92 A retrospective study of patients with urinary tract cancers has deduced that senna may be causally linked.93

Alteration to the bowel structure from laxatives has been described but is another controversial aspect of senna use.11,89 The colon in stimulant laxative users may lose its structure, namely the haustral folds, and this could indicate either neuron or muscle damage may have occurred.94

Interactions

Because of the decreased transit time through the colon it is possible that senna may interact with drugs with which it is co-administered and which are absorbed from this area. In vivo concomitant administration of senna and oestrodiol resulted in reduced serum hormone levels although the effect was not significant.95

Chronic use or abuse of Cassia may lead to hypokalaemia which could potentiate the effect of cardiac glycoside drugs like digitalis or anti-arrhythmics or exacerbate potassium deficiency induced by thiazide diuretics or adrenocorticosteroids.11

Historical uses

As for modern uses.

Cytisus scoparius [Formerly Sarothamnus scoparius]

Broom, Scotch broom

Description

Much branched deciduous shrub to 3 × 2 m, with slender, erect, arching stems and green, more or Family Fabaceae less 5-angled twigs. Leaves trifoliate and petiolate when mature, younger leaves sub- sessile and 1–2-foliate, soft green. Leaflets elliptic to obovate 4–16 mm long, terminal leaflet longer than lateral leaflets. Flowers pea-shaped, usually solitary, rarely paired, in leaf axils. Calyx glabrous, bilabiate, about ¼ length of corolla. Corolla golden yellow, 16–25 mm long. Pods black, many-seeded, oblong, 15–60 mm long with hairy margins. Seeds ellipsoid, brown or greenish brown, about 3 mm long. Flowers late spring to mid-summer.

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Family Fabaceae

Habitat and cultivation

Native to Britain, Europe and Asia, grows in light to medium acid soils in sunny situations. Cytisus is naturalised elsewhere and is often a troublesome weed. It grows from seed or cuttings and is drought and frost resistant.

Parts used

The flowering tops harvested in early spring.

Active constituents

1) Quinolizidine alkaloids (0.10% of fresh plant) mainly (–)-sparteine, (–)17-oxosparteine, (+)-lupanine and derivatives of lupanine. Alkaloid levels are highest in the leaves, much lower in flowers96,97

2) Flavonoids including the isoflavonoids genistein and scoparin, also flavonols including quercitin and isoquercitin98,99

3) Phenethylamines including tyramine and hydroxytyramine, levels much higher in flowers96,100

4) Volatile oil including eugenol, isovaleric and benzoic acids

Also contains tannins, caffeic and p-coumaric acids. The seeds contain lectins.101

Actions

1) Peripheral vasoconstrictor

2) Antihaemorrhagic

3) Diuretic

Scientific information

Broom was used medicinally by the Anglo-Saxons and was at one time an official preparation.

There are very few studies of this herb in recent times and most knowledge comes from traditional use and the observed actions of its best known constituent, sparteine, which has been used in orthodox medicine.

In vitro—The herb has good antioxidant properties.102

Cytisus is a herb with cardiac activity however this activity is not based on glycosides, as in the case of Digitalis and Convallaria, but is due to the alkaloids, mainly sparteine.

Sparteine has been subjected to pharmacological study.1 It reduces the irritability and conductivity of the heart. Its action occurs via the autonomic ganglia, small doses stimulate and large doses paralyse them. It potentiates the effect of adrenaline in raising blood pressure. It also depresses respiration and is a stimulant of uterine contractions (though Potter's suggest this action is unpredictable in inducing labour, Weiss states it is used instead of quinine in obstetric practice and there are many reports of its use as an oxytocic agent1).

The phenethylamines have vasoconstrictor activity.

Medicinal uses

Cardiovascular system

The effect of Cytisus is to reduce overactivity of the heart and so produce a regular, effective heart stroke. The peripheral constriction produces a rise in pressure. Overall venous return and cardiac output benefit:

BHP specific is for functional palpitations with lowered blood pressure.

N.B. Weiss states the herb will not adequately treat absolute arrhythmia or paroxysmal tachycardia.

Reproductive tract

As a vasoconstrictor and anti-haemorrhagic, the herb may find use in the treatment of:

Pharmacy

Three times daily  
Infusion of dried herb –   1–2 g
Tincture 1:5 (45%) –   0.5–2 ml
Fluid Extract (25%) –   1–2 ml

CONTRAINDICATIONS—Pregnancy, hypertension.

Historical uses

Cytisus was considered a cathartic and emetic agent. Used in gout; joint pains in general; liver obstructions; sciatica; tumours. Also for ague; bladder and kidney problems including stones. The oil used for toothache. As an ointment for stitches in the side or spleen pain; for lice.

Galega officinalis

Goat's rue

Description

An erect, leafy, hairless perennial herb growing from 0.5–1 m high in flower. Stems rounded, ribbed, hollow and more or less glabrous. Leaves pinnate with oblong, fine- pointed or notched leaflets 20–50 mm long, in 4–9 opposite pairs; pinnately veined; stipules ovate-lanceolate with 1–3 basal lobes. Flowers in erect axillary or terminal racemes. They are short-stalked and 8–15 mm long. Calyx campanulate with 5 sub-equal teeth, glabrous or with scattered short hairs at the base of the tube and teeth, slightly swollen at the side. Corolla white or pale lilac, 10–13 mm long. Seed pods glabrous, more or less cylindric, 2–3 cm × 4 mm, with thickened parallel veins, containing 2–8 smooth, oblong seeds. Flowers in summer through to autumn.

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Family Fabaceae

Habitat and cultivation

Native to Europe and Asia Minor and cultivated elsewhere. Grown from seed and self-sows. Prefers an open sunny situation and rich, moist soils. Dies back in winter. Drought and frost tender.

Parts used

The herb harvested just prior to or during flowering.

Active constituents

1) Alkaloids including galegine103 and peganine104

2) Saponins of triterpenoid type and β-sitosterol105

3) Flavonoids based on kaempferol and quercitin106

Also contains a bitter compound and tannins.

Actions

1) Hypoglycaemic

2) Galactagogue

3) Diuretic (mild)

Scientific information

Galega has been associated with treating diabetes since the Middle Ages and was used in Europe and other parts of the world.107,108 It was from this herb that metformin, a current drug commonly used to treat type-2 diabetes, was developed.109

In vitro—The herb has significant antibacterial activity to both Gram-positive and Gram-negative organisms.110 A water-soluble fraction inhibits platelet aggregation (it consists of a polysaccharide and protein).111,112

Goat's rue does not contain any known phyto-oestrogenic constituents.113

Galegine is a glucokinin derived from the purine guanidine. It has been identified as a poison to some live-stock if eaten in excess which has led to Galega being listed as a poisonous plant in some countries.114 It is active as a hypoglycaemic agent.115

The name Galega derives from gale-“milk” and ega- “to bring on” a clear acknowledgement of the herb's galactagogic properties. There are no current in vivo evaluations of the herb as an anti-diabetic agent or as a galactagogue but earlier clinical studies had examined these actions.116,117

Medicinal uses

Reproductive tract

Endocrine system

Pharmacy

Three times daily  
Infusion of dried herb –   1–2 g
Tincture 1:10 (45%) –   2–4 ml
Fluid Extract (25%) –   1–2 ml

Galega is particularly used for type 2 or late onset diabetes. The BHP states that its effect is gradual and if the patient is using insulin then this needs to be continued. The treatment regime can be adjusted as the blood and/or urine glucose levels improve.

Precautions and/or safety

Careful monitoring of glucose levels is necessary when treating diabetes.

Historical uses

Used as a footbath for tired feet. The American G. virginiana is also diaphoretic and anthelmintic. This was an official medicine in the United States Pharmacopoeia. Weiss mentions the seeds of G. officinalis as the part used in the treatment of diabetes but does not apparently hold them in very high regard.

Glycyrrhiza glabra

Liquorice, licorice

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Family Fabaceae

Description

A robust erect, hairless perennial to 1.5 m, which dies down in winter. Leaves, mat green, pinnate with 9–17 elliptic to oblong leaflets, 2.5–5 cm, and a terminal leaflet, sticky beneath; stipules minute or absent. Flowers numerous, growing in axillary, long stalked, spike-like clusters. Each flower is bluish or violet, about 1 cm, with a glandular-hairy calyx and an erect standard much longer than the wings or keel. Fruit 1.5–2 cm, oblong, much flattened and hairless. Flowers in summer.

Odour—faint and characteristic; taste—very sweet and mildly aromatic.

Habitat and cultivation

Native to south east Europe, central and south west Asia growing in stony places, dry woods and ditches. Grows easilty from seed. Cultivated commercially in well- drained, rich moist soil. Does best in cold winter climates. May be divided and replanted in autumn. Dies back in winter and does not appear until late spring.

Frost resistant, drought tender.

Parts used

Root and stolons harvested from autumn of the fourth year onwards (preferably). Outer cortex may be stripped or left.

Active constituents118

1) Triterpene saponins predominantly glycyrrhizin (2–25%) which is a mixture of calcium and potassium salts of glycyrrhizic acid, also called glycyrrhizinic acid. Its aglycone 18-β-glycyrrhetic acid (glycyrrhetic acid) also called glycyrrhetinic acid or enoxolone, is present in small quantities and produced on hydrolysis of glycyrrhizin. Other terpenoids have been isolated119–123

2) Flavonoids (approximately 1%) including:

a) flavonones—liquiritigenin, isoliquiritigenin, liquiritin and its apioside, isoliquiritin and licochalcone A

b) isoflavonoids—including glabridin (about 0.2%), glabrene and fomononetin124–131

3) Bitter (glycymarin)

4) Polysaccharides based on a backbone of galactose residues132–134

Also contains up to 45 other phenolic constituents including salicylicates,135,136 a trace of volatile oil, sterols (β-sitosterol137), asparagine, coumarins138 including umbelliferone,139 a trace of tannins and a ketone based on propanone.140

Glycyrrhizin is the predominant constituent of all Glycyrrhiza species, although its content varies widely with geographical location127,141 being up to 4% in European root but much higher in Chinese grown liquorice. Content is also influenced by extraction method for example it is better extracted using 70% ethanol than 50% ethanol.126 Glabridin is a distinctive flavonoid found in G. glabra and helps to distinguish it from the other medicinal varieties, G. uralensis and G. inflata, although all three are closely related. In central Asia where both G. glabra and G. uralensis grow together a hybrid is produced but it lacks glabridin.141

Nutritional constituents

Vitamins: E and B complex, biotin, niacin and pantothenic acid

Minerals: Phosphorus, manganese, iodine, chromium and zinc

Also contains lecithin.

Actions

1) Expectorant

2) Adrenocorticotropic

3) Demulcent

4) Anti-inflammatory

5) Spasmolytic

6) Mild laxative

Scientific information

Glycyrrhiza has been named from the Greek glykos = sweet and rhiza = root. Its medicinal use has a long history, over 4000 years, and is widespread being found in all the major ancient cultures. It has been an official medicine in very many countries as a demulcent and expectorant,1 actions attributed to glycyrrhizin,118 and is approved by German Commission E for the treatment of upper respiratory catarrh and for gastric and duodenal ulcers.

Glycyrrhizin is around 170 times sweeter than sucrose142,143 (a value of 50 times sweeter has been reported elsewhere118). It is widely used in commerce as a flavouring agent (in the tobacco industry, for beverages, as a foaming agent in beer and also in confectionery) apart from being one of the most frequently used herbs worldwide.

There is a vast volume of new research into the herb and its constituents as they appear to have a broad spectrum of activity and may provide the basis for developing new medicines.

Endocrine effects

The adrenal-like effects of Glycyrrhiza have been appreciated for a long time and many studies have helped to elucidate its mode of action.

In vitro—The mechanism of action and the effect of liquorice's constituents, mainly glycyrrhetic acid, on adrenocortical function is seen as two-fold:-

The inhibition of 11β-hydroxysteroid dehydrogenase has further ramifications as the enzyme may be partly responsible for the differentiation of precursor fat cells to adipose cells a process that has been prevented by carbenoxolone, a derivative of glycyrrhizin.150 In vivo liquorice was indeed shown to reduce body fat.151

The isoflavonoids glabridin and glabrene also have endocrine effects and have shown similar benefits to that of HRT in osteoblasts and endothelial cells from post-menopausal women.152,153

In vivo—The measured effects of Glycyrrhiza in normal healthy people, presumed to be due to inhibiting 11β-hydroxysteroid dehydrogenase, are:-

It does not change plasma cortisol and ACTH levels.158 Metabolic changes caused by liquorice or its constituents persist for a short time after ceasing their use.159

The effects of Glycyrrhiza on adrenal function has lead to it, or glycyrrhizic acid, being used as a supportive therapy for conditions of adrenal insufficiency like Addison's disease.118 In fact a case of primary adrenocortical insufficiency was masked due to the patient's excessive consumption of liquorice.160 It may also be useful in treating hyperkalaemia associated with diabetes mellitus.161

Liquorice given to normal pre-menopausal women resulted in:-

The effect of liquorice on male serum testosterone levels is somewhat controversial. Some studies have reported reductions in levels165,166 whilst others found no significant changes.162,167 The latter researchers concluded that moderate Glycyrrhiza intake mainly induces changes in cortisol levels with marginal effects on androgen hormones.

In both men and women, over a range of ages, regular liquorice intake was linked to reduced prolactin levels and a lower response of prolactin production to thyrotropic releasing hormone (TRH).168

Anticancer and Immune modulation

In vitro—Glycyrrhiza and a number of its constituents have been identified as possible anticancer agents169,170 by directly inhibiting the growth of myelogenous and monoblastic leukaemia cells,171–173 prostate,174–178 breast,173,179,180 hepatoma,181 gastric,182 colon183 and lung184 cancer cells.

Constituents in the herb are phyto-oestrogenic185 and can bind to oestrogen receptor sites. They are also able to bind more weakly to progesterone receptor sites186 and this may affect hormone-dependent cancer cells. The flavonoids glabridin, isoliquiritigenin and glabrene in isolation have a biphasic effect on breast cancer cells i.e. they are stimulatory at low dose but cytotoxic at high dose, the latter effect being irrespective of the hormone-dependent status of the cells.187–189 The whole extract does not cause increased proliferation of oestrogen-dependent breast cancer cells190 and binds only weakly to oestrogen receptors.191

Indirectly too the herb may be protective against cancer as constituents are:-

In addition higher levels of glucocorticosteroids have been found to decrease cancer cell proliferation and Glycyrrhiza increases cortisol levels.198

The herb may have some general support for the immune system too. Glycyrrhiza used with Echinacea in vitro increased phagocytosis, the effect of the two herbs being greater than that induced by either one alone.199 Licochalcone-A alters cytokine production and may be immunomodulatory200 and glycyrrhizin increases interferon production.201

In vivo—No trials have specifically used Glycyrrhiza or its constituents to treat cancer but a proprietary preparation, PC-SPES, containing liquorice was hailed for some time as very beneficial for treating prostate cancer. It has since been shown that the preparation was adulterated with pharmaceuticals including an oestrogen analogue and interpretation of the benefits due to the herbs themselves is not possible.202

Liquorice improved immune function by enhanced T-cell production within 24 hours of its having been taken, the effect persisting for days afterwards.203 Used in combination with other herbs it improved the symptoms associated with allergic asthma204 and Familial Mediterranean Fever.205

Gastro-intestinal system

In vitro—Isoliquiritigenin is an antagonist of acid-producing parietal cells in the stomach.206

In vivo—Liquorice was used as a watery paste to treat gastric ulcers in the mid 20th Century. This preparation reduced symptoms, healed ulcers and protected against their future development. The potential for unwanted effects like pseudoaldosteronism (see under Precautions) prompted the development of new compounds from its constituents including carbenoxelone and deglycyrrinized liquorice. The former although effective still had side-effects,207 the latter was useful in the treatment of erosive gastritis, duodenitis and/or ulcers208–212 but newer pharmaceuticals have largely displaced both preparations.

Glycyrrhiza and/or its synthetic derivatives:-

Glycyrrhiza has been used, in combination with other herbs, to successfully treat infantile colic (tea)218 and functional dyspepsia.219,220

Hepato-protective

In vitro—Constituents of the herb:-

In vivo—Japan and Russia have used a preparation containing glycyrrhizic acid for decades to treat:-

A recent review of the use of glycyrrizin in trials to treat chronic hepatitis C indicated it had a limited effect, improved liver function was not sustained on cessation of therapy and there was no reduction in viral load.232

Intravenous administration of glycyrrhizin was used to treat oral lichen planus in hepatitis C patients with some success.233

Antimicrobial

In vitro—The whole extract as well as the main saponins and flavonoids135 are very effective and safe antimicrobials against:-

Licochalcone A has in addition antimycobacterial activity against Mycobacterium tuberculosis, some Legionella species252 and strong activity against Leishmania spp.253

Glycyrrhizin inhibits dental plaque formation254 and enamel dissolution.255

In vivo—Tests using liquorice or its constituents as an antimicrobial in dentifrice have not been clear—with both negative256,257 and positive258 results having been reported.

Anti-oxidant

In vitro—Glycyrrhiza has good anti-oxidant activity.259–261 Seven individual flavonoids, including glabridin, the most abundant and most potent, also have good activity.262–265 Glycyrrhetic acid has both anti-oxidant and pro-oxidant activity, the latter action has been suggested as a mechanism for apoptosis of tumour cells through increased membrane permeability.266

Ex vivo—LDL was protected from oxidation by prior dosing with Glycyrrhiza.267

In vivo—Oxidation of LDL is considered a crucial step toward the development of atherosclerotic lesions. Liquorice given to patients with hypercholesterolaemia was anti-oxidant, increased LDL resistance to atherogenic changes and lowered LDL-cholesterol (5%), triglyceride levels (14%) and systolic blood pressure (10%).268 This latter finding is in contrast to systolic rises in normal, healthy people. The herb may therefore prove beneficial in the treatment of cardiovascular disease. Glycyrrhiza (and glabridin) also reduced LDL oxidation in people with normal lipid levels.267

Anti-inflammatory

In vitro—Glycyrrhiza has a reputation as an anti-inflammatory. Apart from effectively increasing levels of cortisol, the herb has demonstrated inhibition of both 5-LOX and COX-2,269 platelet aggregation270 and some activity against fibroblasts derived from rheumatoid arthritis cells.271

Various of the herb's constituents also inhibit platelet aggregation272, inflammatory cytokines273 and serum complement factors which are commonly involved in chronic inflammation e.g. in autoimmune and allergic reactions.274–277

Topical

In vitro—Glycyrrhiza and/or glycyrrhizin added to a topical preparation increases its free radical scavenging activity and enhances skin protection from oxidative278 and UVB radiation279 damage.

Various flavonoids in Glycyrrhiza inhibit tyrosinase280,281 and in fact liquorice extracts have been used in hyperpigmentation disorders.282

Topical preparations themselves benefit from the herb's anti-oxidant activity as it helps to stabilise them.283

In vivo—Some of Glycyrrhiza's constituents have been tested topically. A gylcyrrhizic acid preparation safely reduced fat deposition (through its inhibition of 11β-hydroxysteroid dehydrogenase284) glycyrrhizin was effective in controlling the symptoms of atopic eczema285 and a mouthwash containing deglycyrrhized liquorice was effective in resolving aphthous ulcers.286

Other

In vitro—Some of the flavonoid constituents of Glycyrrhiza inhibit the enzymes xanthine oxidase (associated with gout) and monoamine oxidase (associated with neuron function)138,287 and inhibit the re-uptake of serotonin.288 The latter two observations may give the herb benefits for use in depression.

The polysaccharide fraction is immunostimulatory.

In vivo—The mineralocorticoid properties of liquorice derivatives have been used for treating hypotension.289

Liquorice was used with the antibiotic, nitrofurantoin, in the treatment of urinary tract infections where it increased urinary elimination of the antibiotic, reducing its side effects.290

The herb is considered a tonic and has wide applicability. It is also a suitable addition to children's prescriptions to improve the taste.

Medicinal uses

Respiratory tract

Gastro-intestinal tract

Musculoskeletal

Skin

Endocrine system

Glycyrrhiza's support of adrenal function through decreasing hormone catabolism, supports its anti-inflammatory effect, and gives it a use in:

Pharmacy

Three times daily  
Decoction –   1–4 g
Fluid Extract (20%) –   2–5 ml

At recommended doses Glycyrrhiza is considered a safe herb and has no teratogenic or mutagenic activity. The safe level of glycyrrhizic acid is set at 0.2 mg/kg per day e.g. 12 mg for a 60 kg person equating to 6 g of liquorice a day based on a glycyrrhizin content of 0.2%.291 Most authorities have set maximum safety limits much higher for instance the Dutch Nutrition Council level is 200 mg glycyrrhizic acid a day291 and German Commission E has specified 100 mg glycyrrhizin a day. Individual differences in absorption, sensitivity and metabolic rate would also affect these limits.

CONTRAINDICATIONS—Hypertension, pregnancy, hypokalaemia, cirrhosis of the liver. Large doses of liquorice should not be used for more than 6 weeks.

Pharmacokinetics

Glcyrrhizin, which is considered the main active constituent in liquorice, seems to have poor bioavailability from the whole extract.292 After ingestion it is hydrolysed to glycyrrhetic acid in a two-step process by gut flora in the colon and for each person this process will vary according to their flora. Glycyrrhetic acid is well absorbed and its level rises in plasma soon after liquorice ingestion, taking 12 hours to reach a maximum. It is transported to the liver by a protein carrier where it is conjugated before being secreted into bile. On reaching the colon a second time re-absorption occurs after the flora have once again hydrolysed the conjugates and so glycyrrhetic acid is recycled,293 a process called enterohepatic cycling, and this gives rise to a second plasma peak of glycyrrhetic acid some time later. This process could cause a cumulative effect in plasma levels.294 It is likely that transit time in the bowel also alters the level of re-absorption, a slow transit tending to raise plasma levels.147

A small amount of glycyrrhizin is absorbed intact and excreted in urine within 24 hours, the main urinary metabolite being glcyrrhetic acid, however, only about 1–2% is excreted by this route.295,296 The urinary metabolite is detectable for some time after liquorice intake is stopped (5 days for chronic intake and up to 51 hours after a single large dose).297

The study of the flavonoids in vitro suggests liquiritin is poorly absorbed but it too appears to undergo changes by gut flora into liquiritigenin and davidigenin which are well absorbed.298

Precautions and/or safety

Blood pressure rises due to Glycyrrhiza may be significantly higher in people with essential hypertension (one study found the average rise was 15.3 mm Hg systolic and 9.3 mm Hg diastolic pressure but the individual range is wide), gender is not a factor in this increase.155,299 A high salt intake exacerbates liquorice-induced hypertension.300

In high enough doses or with chronic use the adrenocortical effects can lead to an excessive increase in potassium loss and sodium and water retention a condition called pseudoaldosteronism. It results in hypokalaemic myopathy, oedema, hypertension and metabolic alkalosis.301–308 Pseudoaldosteronism can occur with no attendant hypertension.309

Various forms of liquorice use can cause hypokalaemic myopathy but symptoms disappear in most cases by refraining from further use.310 Most adverse event reports have occurred from the consumption of excessive or chronic liquorice confectionery or in people who already had existing health problems when they used reasonable amounts of the herb.311–314 However pseudoaldosteronism has been recorded in healthy people taking as little as 7 g of liquorice, equating to 500 mg of glycyrrhizic acid, daily for a week315 and symptoms have been reported from just using a liquorice mouthwash or chewing gum.316,317 Interestingly, aqueous extracts are associated with fewer and less severe side effects than reported for the equivalent amount of herb in confectionery form.318

More serious side-effects attributed to liquorice use include:-

There appears to be a range of sensitivities to Glycyrrhiza and/or its constituents.

As 11β-hydroxysteroid dehydrogenase can act as a detoxifying enzyme for external chemicals liquorice by its inhibition of this enzyme may counter this protective effect.333

Reported reduction in men's testosterone levels occurred with doses of 7 g liquorice daily (0.5 g glycyrrhizic acid).165

In pregnancy—a retrospective study associated a shorter gestation and increased pre-term deliveries (less than 37 weeks gestation) in women consuming large amounts of liquorice confectionery (estimated to be more than 500 mg glycyrrhizin per week).334,335 Birth weight and maternal blood pressure were not affected but fluid retention could be relevant to maternal hypertension.

Although there have been a few fatalities linked to the herb's use, in the majority of cases side-effects that have been recorded, whether serious or not, have been reversible. It may take anywhere from weeks to months for disturbed biochemistry to return to normal.

Interactions

In vitro—Glycyrrhiza and some of its constituents (not glycyrrhizin) inhibit CYP3A4.336–338 Glabridin also inhibits isozymes CYP2B6 and CYP2C9.339 There is the potential for drug/herb interactions based on these effects.

In vivo—Other possible and/or reported interactions are:-

In vitro Glycyrrhizic acid complexes with lappaconitine, an antiarrhythmic agent, although no in vivo problems have so far been reported.343

Historical uses

Dropsy; to prevent thirst (diabetes?); “all diseases of breast and lungs”; tuberculosis; dry cough, hoarseness; mild laxative; kidney pain; ulcerated kidneys and bladder; strangury; heat of urine. Externally used in eyes for “rheumatic distillations” (powder).

Melilotus officinalis

Melilot, sweet clover

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Family Fabaceae

Description

A biennial herb with a woody tap root. Stems more or less glabrous below, sparsely hairy above, decumbent or erect to 1.5 m high in flower. Leaves pinnately trifoliate, sparsely hairy when young otherwise glabrous, petioles 5–25 mm long, leaflets narrowly elliptic or obovate, serrate, 10–25 mm long. Flowers numerous, yellow, in lax and slender racemes. Corolla 4–6 mm long, wings greater than keel. Pod glabrous, about 3 mm long, 1–2 seeded, transversely rugose, seeds light brown, 2–3 mm long. Flowers from spring to summer. It may be distinguished from the very similar M. albus by the latter's white flowers and reticulately veined seed pods.

Odour—of coumarin, sweetish; taste—bitter, somewhat salty and pungent.

Habitat and cultivation

Native to Europe and Asia, melilot grows wild in many countries, in dry waste places and near the coast. It is grown from seed and self-sows. Drought and frost resistant.

Parts used

The herb, harvested during flowering and dried carefully.

Active constituents

1) Coumarins (up to 1.4%) including free coumarin, o-coumaric acid, dihydroxycoumarin, melilotin, melilotic acid and melilotol.344 These develop on drying

2) Flavonoids (about 0.1%)345 including robinin

3) Tannins

Phenolics other than the flavonoids345 and saponins have also been isolated from Melilotus.346

Actions

1) Spasmolytic

2) Carminative

Scientific information

Melilotus was known to and used by the 2nd century physician Galen. It was at one time an official medicine. In the 1920's attention was drawn to the herb when cattle grazing it developed haemorrhages. Studies isolated the causative factor, dicoumarol, and from this was developed the antithrombotic warfarin.347 Melilotus develops dicoumarol through fermentation as it decomposes and it is not actually a component of the properly prepared herb.348

In vitro—Melilotus has some limited anti-oxidant and anti-inflammatory activity due to its phenolic content.345,349

The coumarins are important to the activity of the herb and they had been shown to be anti-oedematous and anti-inflammatory, increasing blood and lymph flow and helping to repair damaged blood vessel walls.350 Ex vivo and in vivo the coumarins are absorbed through the skin and may act on the local circulation.

In vivo—Melilotus has been used with other herbs to treat chronic venous insufficiency with both subjective and objective measures being significantly improved by topical application351 and with internal treatment.352

Preparations containing the coumarins and/or the whole herb were able to reduce lymphoedema caused by node removal in the treatment of metastatic cancer.353,354 The reduced oedema though modest (5%) was significant.

An internal preparation containing the herb was developed in Italy and marketed as Cellasene for reducing cellulite. The action of Melilotus in the product was intended as a circulatory stimulant to reduce oedema.355 Reported trials of the product have given contradictory outcomes with a few claiming efficacy whilst at least one found it failed.356

The herb is used in other traditions as a sedative.357

Medicinal uses

Cardiovascular system

Pharmacy

Infusion dried herb –   1–2 teaspoons per cup boiling water (dose 3–4 cups a day—Weiss)
Tincture 1:5 (45%) –   1–5 ml†
Fluid Extract (25%) –   0.6–2 ml

Precautions and/or safety

In vivo—Studies reported only minor side effects like transitory gastro-intestinal problems.354

Coumarin (benzo-α–pyrone), which has been used as a food additive, itself has no anti-coagulant activity and adverse effects in humans occur rarely and with high doses only. The European Commission safety limit has been set at 0.1 mg/kg/day, probably a very conservative level given that much larger doses have been used for months at a time without problems. Doses of coumarin of up to 7000 mg/day in humans have been well tolerated and where liver enzymes have risen in patients subjected to very high doses, these are reduced on cessation of the drug. Topical application results in very much lower systemic levels.358 Coumarin Suggested dosage based on German Commision E recommendation. Alcohol strength based on that used for coumarin-containing Trifolium pratense. is considered to be non-genotoxic and although hepatotoxicity has been reported in rodents this appears to be a peculiarity of their metabolism.

There are suggestions that the herb may increase bleeding time and should not be used prior to surgery but this is speculative, there are no reports of this having occurred in the literature.359

Interactions

The herb could potentially interact with blood thinning agents like warfarin360,361 but to date this has not been reported and as the herb contains coumarins with no significant anti-coagulant activity the interaction would seem very unlikely.

Historical uses

In combination with other herbs as an ointment or poultice to soften all swellings; the juice as eye drops to clear sight. Also used externally for abdominal and rheumatic pain, loss of senses and apoplexy. As an analgesic for head and ear aches. For flatulence.

Piscidia piscipula [Formerly P. erythrina]

Jamaican dogwood, fish poison tree

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Family Fabaceae

Description

Evergreen shrub 5 × 2.5 m. Bark yellowish or greyish brown. Stems erect, slender. Leaves divided into 3–4 pairs of leaflets, ovate to obovate, up to 10 cm long, undulate or slightly toothed. Flowers small, pea-shaped, white, striped red. Fruit a pod to 10 cm long with longitudinal wings.

Habitat and cultivation

Originally from the West Indies and southern Florida Piscidia grows in moist, well-drained soil and sunny sheltered situations. It is drought and frost tender. It is propagated from stratified seed.

Parts used

The root bark.

Active constituents

1) Isoflavonoids over 20 have been identified some being complex, called coumaronochromones, and others containing amino groups.362 The main isoflavonoids are erythbigenin, piscidone, ichthynone, jamaicin, genistein, lisetin and rotenone363–370

2) Organic acids including piscidic, fukiic and methylfukiic acids

Also contains tannins and β-sitosterol.

Some variability in the constituents occurs with the geographical area in which the plant grows.

Actions

1) Sedative

2) Antitussive

3) Spasmolytic

4) Anti-inflammatory

5) Anodyne

Scientific information

Western interest in this herb appears to date back to the 1840s. Whilst the actions of Piscidia are utilised by herbalists, little detail of the pharmacology is available.

In vitro—Piscidia is used in Guatemala to treat fungal infections and this use has been verified.371

Rotenone, an insecticide whose activity is based on its ability to interfere with oxygen metabolism via mitochondria, is a neurotoxin.372 There is current concern that it may contribute to the development of Parkinson's disease based on animal and in vitro studies.373

In vivo—There are no human trials available but animal studies have indicated the herb has spasmolytic activity, is hypotensive and depressant to the myocardium.

Piscidia used as a fish poison, was thrown into the water, causing fish to float to the surface where they were easily caught. The active constituent in this process is considered to be piscidic acid.

Medicinal uses

Nervous system

Primarily active on nerve tissue making it useful for:

BHP specific for insomnia due to neuralgia and nervous tension.

Reproductive tract

Pharmacy

Three times daily  
Decoction of dried herb –   2–4 g
Tincture 1:5 (45%) –   5–15 ml
Fluid Extract (60%) –   2–8 ml

CONTRAINDICATIONS—Pregnancy, bradycardia, cardiac insufficiency.

Historical uses

Asthma; whooping cough; toothache.

Trifolium pratense

Red clover

Description

Erect or decumbent perennial not rooting at the nodes, with stems sparsely hairy below and moderately or densely hairy in the upper parts. Leaves alternate, trifoliate, usually moderately hairy on petioles and under surface of leaflets, and more or less glabrous on upper surface. Petioles up to 200 mm long; leaflets ovate, elliptic or obovate, usually more or less entire with a crescentic spot towards base, about 15–40 mm long. Inflorescence terminal, spicate, globose to ovoid, usually sessile and with 2 leaves immediately below it. Flowers numerous, sessile, corolla pink or purple-pink, 10–16 mm long. Pod glabrous and straight, 2–3 mm long 1-seeded. Flowers from spring to autumn.

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Family Fabaceae

Habitat and cultivation

Native to Europe, West Asia and North Africa, red clover is common throughout the world, both cultivated and naturalised in pasture, waste places and gardens.

It is grown from seed and self-sows in light, well-drained soils, in open sunny situations. It is grown instead of lucerne in areas with a cool spring climate, but will grow in any ordinary garden soil as long as it does not get too dry in summer. Commonly grown as fodder. Frost and drought resistant.

Parts used

The flower heads. Most commercial products also contain some of the small leaflets.

Active constituents374

1) Flavonoids

a) mainly isoflavones (up to 0.6%) over 20 have been identified including formononetin and biochanin-A with lower levels of daidzein, genistein and pratensein375–379

b) flavones380

2) Phenolic acids including salicylic, coumaric and caffeic acids

3) Procyanidins—polymers based on epicatechin and catechin381

4) Volatile oil containing more than 40 compounds

Also contains sitosterol, fatty acids and long chain hydrocarbons and alcohols.

The levels of isoflavone may vary over the season, daidzein and genistein levels are higher in mid-summer whilst formononetin and biochanin-A peak in autumn.382 Higher ambient levels of UV-B radiation increase the content of the latter isoflavones and caffeic acid also.383 Leaves have the highest content of isoflavones and contain some not found in the flowers.375 Flowers have the lowest isoflavone levels of all the aerial parts of the plant.384 Many cultivars of Trifolium exist which may differ in their isoflavone concentrations but site and plant age, plant-part, growing conditions and maturity at harvest all contribute to a variable chemical make-up.

Nutritional constituents

Vitamins: A, B-complex, C, F and P

Minerals: Rich in magnesium, calcium, potassium and copper also some selenium, manganese, sodium and zinc

Actions

1) Dermatological agent

2) Mild antispasmodic

3) Expectorant

4) Alterative

Scientific information

Red clover is of interest to the agricultural sector as a food crop for livestock and for its value in soil improvement. Recent interest in the medicinal value of the herb is due to its good phyto-oestrogenic potential, the isoflavones being structurally similar to 17β-oestradiol, and it is being trialled as a safer treatment for menopausal symptoms than HRT. The leaves have a much higher level of hormone-like constituents and they have been used in the main for commercial extracts, being further processed to enhance the isoflavone levels so that they represent 30% or more of the total.376 Traditionally this part of the herb was not used, neither was Trifolium used for its hormone-like properties. Very little recent research has in fact been carried out into its traditional uses.

Hormonal

In vitro—The flowers do have significant phyto-oestrogenic activity385 although most studies have used isoflavone-enriched extracts. The extracts bind to both α- and β-oestrogen receptor sites386 (and also to those for progesterone and androgen)375,387 and are deemed to have a high enough hormone activity to act like synthetic oestrogens (HRT).388 Of the isolated isoflavones genistein has the strongest oestrogenic activity.389

In vivo—Trials using isoflavone-rich Trifolium, with or without the isoflavones from other plant sources, have reported benefits for post-menopausal women in:-

Some studies failed to corroborate improvements in menopausal symptoms.394,395 Extracts did not improve short term cognitive function in post-menopausal women.396

Cardio-vascular

Epidemiological studies have suggested isoflavone rich diets, particularly soy-based ones, are preventative for cardiovascular disease.

In vitro—The herb increases nitric oxide synthesis in endothelial cells suggesting a possible benefit for blood vessel tone and reduced atheroma formation.397

Ex vivo—Blood vessel walls benefited from isoflavone supplementation.398

In vivo—Trials to determine hormonal benefits also analysed effects of isoflavones derived from Trifolium alone or in combination with other isoflavone sources, for cardiovascular health.

Isoflavone supplements have been given to woman at different stages in their reproductive life. They improved lipid (triglyceride,399 HDL cholesterol390,392,400) and homocysteine390 levels in post-menopausal women with little, or no, benefit for pre-and peri-menopausal women.400–402

A number of reviews of the above clinical trials have commented on discrepant results for cardiovascular and menopausal symptom relief.403–406 Inconsistencies may be due to variability in the chemistry and/or quality407 of different extracts used or their method of processing.375 There has been better consistency across studies examining Trifolium extracts in maintaining bone and arterial health in post-menopausal women.408

A quite different Trifolium isoflavone preparation, one rich in formononetin, reduced arterial stiffness in both genders without affecting blood pressure levels409 whilst the isolated isoflavone, biochanin-A, lowered low-density lipoprotein in men but not in women.410

Anticancer

Traditionally Trifolium has been used in treating cancers and this is supported by epidemiological studies showing cultures with isoflavone-rich diets have a lower incidence of prostate cancer, and also of benign prostatic hyperplasia.411

In vitro—The isoflavones stimulate differentiation of cancer cells,412 may reduce the risk of oestrogen-related carcinogenesis413 and inhibit COX activity which has been linked with, among other things, cancer development.414 Biochanin-A protects cells from external chemical carcinogens.378,415

In vivo—There is evidence to suggest that red clover isoflavones are beneficial in treating prostatic cancer.411,416

Other

Red clover is anti-oxidant in vitro,315,387,417 an action attributed to the isoflavones and phenols418 however in vivo isoflavones did not improve the antioxidant status in women.400

Medicinal uses

Respiratory tract

Skin

Used in the treatment of skin problems where it may act as an alterative for:

Externally

It can be used topically too for the treatment of the above skin problems.

Pharmacy

Three times daily  
Infusion –   2–4 g
Tincture 1:10 (45%) –   1–2 ml
Fluid Extract (25%) –   2–4 ml

For external use an infusion or the fluid extract can be used directly or added to an ointment base to give a 10–15% concentration of herb—volume to weight.

Pharmacokinetics

Liver microsomes convert biochanin-A and formononetin into genistein and daidzein respectively413 and serum levels of isoflavones appear to have a relatively long half-life.419 In vivo the isoflavonoids are mainly conjugated in the liver, undergo enterohepatic cycling and are excreted in bile and urine.420,422

Precautions and/or safety

The isoflavone-rich extracts used in these trials, in some cases amounting to a daily intake of between 80–160 mg of red clover derived isoflavones, were without side-effects. Red clover is considered safe.421,422

In vitro—Breast cancer cells were induced to proliferate when exposed to a commercial preparation of Trifolium creating concern over their suitability for use in women with hormone-dependent breast cancer.423 On the other hand the isoflavones inhibited the production of mutagenic metabolites from endogenous hormones which could give them a protective role against increased cancer risk.413

In vivo—Checks on hormone levels and breast density changes in women at risk for the disease found isoflavones did not alter these parameters and they are not therefore considered to increase the risk of breast cancer.394

Interactions

In vitro—Trifolium inhibits CYP3A4.424

Some sources caution against using the herb with anticoagulant therapy because of its coumarins (see Melilotus). However the coumarin content is low and dicoumarol has not been identified in it. There are no reported interactions of Trifolium with any medicines.

Historical uses

The herb has a folklore tradition of being used in the treatment of cancerous growths.

Trigonella foenum-graecum

Fenugreek

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Family Fabaceae

Description

An erect almost hairless annual, 15–50 cm tall. Leaves alternate, trifoliate, oblong to ovate, toothed near the apex. Flowers whitish-yellow, stalkless, solitary or paired in the axils of the upper leaves. Each flower 1–1.5 cm, in a hairy calyx with equal, linear, lance-shaped teeth. Fruit is a small, erect, linear, hairless pod, 7–10 cm, progressively narrowing to a slender beak, 3–5 cm.

Odour—spicy, characteristically of curry; taste—somewhat bitter and seeds are mucilaginous when chewed.

Habitat and cultivation

Native to Asia and introduced, and sometimes naturalised, in much of Southern Europe. Always grown from seed which germinates easily. Grows in any ordinary garden soil, like a dwarf pea. Sometimes grown as a fodder crop and is used in veterinary treatments. Drought and frost tender.

Parts used

The dried mature seed.

Active constituents

1) Steroidal saponins including diosgenin (up to 0.9%),425 yamogenin, methyl-protodioscin, methyl-protodeltonin426,427 and a number of other furostanol saponins428,429

2) Alkaloids including trigonelline (up to 0.36%)

3) Mucilage (up to 30%)

4) Volatile oil

5) Flavonoids including vitexin, quercetin, luteolin and naringenin430

Also contains a high level of protein431 including the unusual amino acid 4-hydroxyisoleucine432 and seven essential amino acids,433 a number of fatty acids, a derivative of β-sitosterol,434 phytate435 and dietary fibre (up to 51%) containing galactomannan, some of which is comprised of mucilaginous fibre and the rest is neutral fibre.436

The total phenolic content of Trigonella is around 5% of its dry weight.437

Nutritional constituents

Vitamins: A, C and D as well as B1, B2 and niacin Minerals: Calcium, phosphorus and iron

Also contains choline, lecithin and an oil resembling cod liver oil.

Actions

1) Hypoglycaemic

2) Laxative

3) Demulcent

4) Expectorant

5) Galactagogue

6) Nutritive

7) Antipyretic

8) Orexigenic Topically

9) Emollient

10) Vulnerary

Scientific information

Trigonella was used by the ancient Egyptian, early Greek and Roman civilisations as a medicinal and culinary herb—the name foenum graecum means “Greek hay”—and has long traditional use in many countries both as a medicine and as a spice. The herb has been an official medicine and is approved by German Commission E to stimulate appetite and as a topical anti-inflammatory.

Apart from its hypoglycaemic properties, which are the focus of current interest, it is also seen as a replacement source of the steroidal saponin, diosgenin, as yams have become too expensive.438 Other parts of the plant are also used as a food, the aerial parts are in fact a richer source of phenols (anti-oxidants).439 Traditionally the herb was used to aid convalescence, possibly because of its rich nutritional content.

Hypoglycaemic

The seeds have been used in Eastern cultures to treat diabetes and hypercholesterolaemia and it is this aspect of Trigonella that has been most studied in recent times.

The alkaloid trigonelline was believed to be the active constituent in glucose control but more recent studies point to the fibre (combined mucilaginous and neutral fibre) and gum as possibly stronger hypoglycaemic agents. The proposed mechanism of action, based on animal experiments, is through delayed gastric emptying with direct interference of intestinal glucose absorption,440 the fibre content slowing down glucose uptake, and possibly also through activation of insulin signalling in adipocytes and liver cells.441

In vitro—4-hydroxyisoleucine increases glucoseinduced insulin release from β-cells of Islets of Langerhans442 and it too may make a contribution to improved glucose metabolism.

In vivo—Trigonella used to treat non-insulin dependent (type 2) diabetes improved glucose control, both fasting and postprandial levels, and reduced glycosuria, glycated haemoglobin and insulin levels.443–448 The results of using Trigonella were comparable to dietary control and exercise but with the added advantage of decreased insulin resistance.445,449 However, blood sugar levels in severe type-2 diabetes were more resistant to change.457

Trigonella was also beneficial in the management of type 1 or insulin dependent diabetes giving improved glucose tolerance as well as reduced fasting blood glucose levels and glycosuria.450

The whole seeds appear to have the strongest hypoglycaemic effect compared to their isolated constituents or the leaves and even after being cooked they still retain some activity.444,447 There are a number of reviews of the clinical trials to-date on Trigonella in the treatment of diabetes that conclude in the main the herb shows good potential.436,451–453

4-hydroxyisoleucine improved the rate of glycogen re-synthesis post-exercise in trained athletes without increasing insulin levels.454

Hypolipidaemic

In vivo—A number of clinical trials on patients with diabetes and/or hyperlipidaemia reported reduced cholesterol levels of between 15–33%,447,455,456 reduced LDL and serum triglycerides and HDL levels that rose449 or were unchanged.448,455

Blood glucose and lipid levels in normal volunteers have been more variably affected by fenugreek with some studies reporting an improvement447 whilst others found no change.457

Galactagogue

In vivo—The traditional use of Trigonella in increasing milk production in lactating women has been supported by an observed increase in milk volume of around 20%.458 Increased lactation was reported as occurring within 24–72 hours of taking the herb.459

Other

In vitro—Fenugreek is also:-

The constituents diosgenin (see Dioscorea villosa)465,466 and protodioscin427 have anticancer propertites.

In vivo—Trigonella was successfully used topically as part of a mixture to treat head lice.467

Medicinal uses

Respiratory tract

Gastro-intestinal tract

Reproductive tract

Externally

Its local healing and anti-inflammatory effects are used in poultices to treat:

Pharmacy

Three time daily. The German Commission E recommendation is:-

Dried herb –   up to 2 g
Tincture 1:5 –   maximum 10 ml
Fluid extract 1:1 –   maximum 2 ml

Externally as a poultice 50 g seed: 250 ml water, bring to the boil and apply to bruises, swellings, boils, ulcers and suppurating wounds.

The studies conducted on the hypoglycaemic action of the seeds used between 15–100 g a day of powdered seed whilst a dose of 100 g per day of the defatted seed powder was used in treating type 1 diabetes.

Precautions and/or safety

The herb is not genotoxic in standard tests.468 Clinical trials reported side effects included mild gastro-intestinal discomfort but even long term use of the herb was not associated with significant side-effects.443

Although it has been suggested fenugreek could increase bleeding time there are no reports of such adverse reactions and measurements on platelet aggregation and fibrinolytic activity showed no changes.457

There have been only 2 reported cases of severe allergy to fenugreek, one due to inhalation of the powdered herb and the other from a topical application.469

In cultures where unusually large quantities of seeds may be consumed it is possible they may contribute to the development of anaemia due to the fibre inhibiting iron absorption.470

Ingestion of fenugreek can lead to an odour in urine that has been confused with “maple syrup urine disease”.471,472 This disease is due to an inborn error of the metabolism of branched amino acids and causes production of sotolone, also present in maple syrup and fenugreek, which is responsible for the smell. Women using the herb to aid lactation or childbirth may have babies who, because of this odour, are erroneously suspected of having the disease.473

Interactions

Trigonella may contribute to excessive hypoglycaemia if used with similar acting pharmaceuticals.

There has been one case reported of an interaction between warfarin and fenugreek-boldo, the coumarin content of both being cited as the likely cause of an increased tendency to anticoagulation (raised INR).474 Neither herb has significant coumarin levels. Further warnings relate to the potential for interactions with any drug with anticoagulant properties.475,476 However no drug interactions have actually been reported.456

Historical uses

To cleanse breast, chest and lungs; for imposthume, ulcer or stoppage in uterus; to aid childbirth; to prevent fevers; comfort the stomach; diabetes; scrofula; rickets; gout; anaemia; post-infection convalescence; neurasthenia; baldness (All conditions except fever or headache.)

_______________

†The constituents of the two varieties of Cassia only differ in their quantity of these constituents. C. acutifolia pods contain 2.5–4.5% and C. angustifolia 1.2–2.5% hydroxyanthracene glycosides (calculated as sennoside B) whilst leaf content for both is a minimum of 2.5%.

†Suggested dosage based on German Commision E recommendation. Alcohol strength based on that used for coumarin-containing Trifolium pratense.