Figwort

Summary and Pharmaceutical Comment

The chemistry of figwort is well studied. Little scientific evidence was located to justify the herbal uses. In view of the lack of toxicity data and possible cardioactive properties, excessive use of figwort should be avoided.

FSpecies (Family)

Scrophularia nodosa L. (Scrophulariaceae)

Synonym(s)

Common Figwort, Scrophularia

Part(s) Used

Herb

Pharmacopoeial and Other Monographs

BHP 1983(G7)

Legal Category (Licensed Products)

Figwort is not included in the GSL.(G37)

Constituents

The following is compiled from several sources, including General Reference G62.

Amino acids Alanine, isoleucine, leucine, lysine, phenylalanine, threonine, tyrosine and valine.(1)

Flavonoids Diosmetin, diosmin and acacetin rhamnoside.(2)

Iridoids Aucubin, acetylharpagide, harpagide, harpagoside, isoharpagoside, procumbid and a catalpol glycoside.(3–5) Figwort is stated to have the same qualitative iridoid composition as devil's claw, but about half the content of harpagoside.

Acids Various acids, including caffeic acid, cinnamic acid, ferulic acid, sinapic acid and vanillic acid, present as both esters and glycosides.(6, 7)

Food Use

Figwort is not used in foods.

Herbal Use

Figwort is stated to act as a dermatological agent and a mild diuretic, and to increase myocardial contraction. Traditionally, it

has been used for chronic skin disease, and specifically for eczema, psoriasis and pruritus.(G7, G64)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below.

Dried herb 2–8 g by infusion.(G7)

Liquid extract 2–8 mL (1 : 1 in 25% alcohol).(G7)

Tincture 2–4 mL (1 : 10 in 45% alcohol).(G7)

Figure 1 Selected constituents of figwort.

Figure 2 Figwort (Scrophularia nodosa).

268

Figure 3 Figwort – dried drug substance (herb).

Pharmacological Actions

In vitro and animal studies

The iridoid glycosides aucubin and catalpol have been documented to exert a purgative action in mice.(8) Cardioactive properties

and anti-inflammatory activity have been claimed for harpagide and the other iridoid constituents (see Devil's Claw).(G62)

Clinical studies

There is a lack of clinical research assessing the effects of figwort and rigorous randomised clinical trials are required. The iridoids are stated to be bitter principles.(G62)

Side-effects, Toxicity

None documented. However, there is a lack of clinical safety and toxicity data for figwort and further investigation of these aspects is required.

Figwort 269

Contra-indications, Warnings

Figwort should be avoided in ventricular tachycardia.(G7)

Drug interactions	None documented. However, the potential for
preparations of figwort to interact with other medicines
administered concurrently, particularly those with similar or
opposing effects, should be considered.
Pregnancy and lactation The safety of figwort has not been
established. In view of the lack of pharmacological and toxicity
data, use of figwort during pregnancy and lactation should be		F
avoided.

References

1 Toth L et al. Amino acids in Scrophulariaceae species. Bot Kozl 1977; 64: 43–52.

2Marczal G et al. Flavonoids as biologically active agents and their occurrence in the Scrophulariaceae family. Acta Pharm Hung 1974: 44 (Suppl. Suppl.): 83–90.

3Swann K, Melville C. Iridoid content of some Scrophularia species. J Pharm Pharmacol 1972; 24: 170P.

4Swiatek L. Iridoid glycosides in the Scrophulariaceae family. Acta Pol Pharm 1973; 30: 203–212.

5Weinges K, Von der Eltz H. Natural products from medicinal plants. XXIII. Iridoid glycosides from Scrophularia nodosa L. Justus Liebigs

Ann Chem 1978; 12: 1968–1973.

6 Swiatek L. Phenolic acids of underground parts of Scrophularia nodosa. Pol J Pharmacol Pharm 1973; 25: 461–464.

7 Swiatek L. Pharmacobotanical investigations of some Scrophulariaceae species. Diss Pharm Pharmacol 1970; 22: 321–328.

8Inouye H et al. Purgative activities of iridoid glucosides. Planta Med 1974; 25:285– 288.

Frangula

Summary and Pharmaceutical Comment

The chemistry of frangula is characterised by the anthraquinone glycoside constituents. The laxative action of these compounds is well recognised and supports the herbal use of frangula as a laxative. The use of non-standardised anthraquinone-containing preparations should be avoided,

F since their pharmacological effect will be variable and unpredictable. In particular, the use of products containing combinations of anthraquinone laxatives should be avoided.

Species (Family)

Frangula alnus Mill. (Rhamnaceae)

Synonym(s)

Alder Buckthorn, Rhamnus frangula L., Frangula nigra Samp.

Part(s) Used

Bark

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E (Buckthorn)(G3)

ESCOP 2003(G76)

EMEA HMPC Community Herbal Monograph(1)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

Figure 1 Selected constituents of frangula.

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G2, G6, G59 and G62.

Anthraquinones 3–7%. Frangulosides as major components including frangulin A and B (emodin glycosides) and glucofrangulin A and B (emodin diglycosides); emodin derivatives including emodin dianthrone and its monorhamnoside, palmidin C (see Rhubarb) and its monorhamnoside, emodin glycoside; also glycosides of chrysophanol and physcion, and various free aglycones.

Other constituents Flavonoids and tannins.

Food Use

Frangula is listed by the Council of Europe as a natural source of food flavouring (category N4). While this category recognises the use of frangula as a flavouring agent, it indicates that there is

insufficient information available to classify it further into categories N1, N2, or N3.(G16)

Herbal Use

Frangula is stated to possess mild purgative properties and has been used traditionally for constipation.(G2, G6, G7, G8, G64)

The European Medicines Agency Committee on Herbal Medicinal Products (HMPC) has adopted a Community Herbal monograph for frangula. The monograph includes indications for short-term use of frangula in cases of occasional constipation.(1)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below.

Dried bark 0.5–2.5 g.(G6)

Figure 2 Frangula (Frangula alnus).

270

Figure 3 Frangula – dried drug substance (bark).

Liquid extract 2–5 mL (1 : 1 in 25% alcohol) three times daily.(G7)

Pharmacological Actions

The pharmacological activity of frangula can be attributed to the anthraquinone glycoside constituents. The laxative action of these compounds is well recognised (see Senna).

Side-effects, Toxicity

See Senna for side-effects and toxicity associated with anthraquinones.(G20)

The EMEA HMPC Community Herbal Monograph for frangula includes the following information.(1) There are no studies on single dose toxicity, on repeated dose toxicity, on reproductive toxicity or on carcinogenicity. Different frangula extracts were shown to be genotoxic in several in vitro systems (bacterial mutation, chromosomal aberration and DNA-repair in mammalian cells). No increases in mutations were observed in a gene mutation assay with mammalian cells. For emodin, the main laxative principle of frangula, signs of a genotoxic potential were observed in several systems (bacteria and mammalian cells in vitro). Other anthraquinone constituents also gave positive results in limited experiments.

Contra-indications, Warnings

See Senna for contra-indications and warnings associated with anthraquinones.

The EMEA HMPC Community Herbal Monograph for frangula states the following contra-indications and warnings.(1)

Contra-indications Not to be used in cases of intestinal obstruction and stenosis, atony, inflammatory colon diseases (e.g. Crohn's disease, ulcerative colitis), appendicitis, abdominal pain of unknown origin, severe dehydration states with water and electrolyte depletion.

Precautions As with all laxatives, frangula bark should not be given when any undiagnosed acute or persistent abdominal symptoms are present. If laxatives are needed every day, the cause of the constipation should be investigated. Long-term use of laxatives should be avoided. Use for more than two weeks requires medical supervision. Chronic use may cause pigmentation of the colon (pseudomelanosis coli) which is harmless and reversible after drug discontinuation.

Frangula	271
Abuse, with diarrhoea and consequent fluid and electrolyte
losses, may cause: dependence, with possible need for increased
dosages, disturbance of the water and electrolyte (mainly
hypokalaemia) balance, an atonic colon with impaired function.
Intake of anthranoid containing laxatives exceeding short-term
use may result in an aggravation of constipation.
Hypokalaemia can result in cardiac and neuromuscular
dysfunction, especially if cardiac glycosides, diuretics or corticos-
teroids are taken. Chronic use may result in albuminuria and
haematuria.
In chronic constipation, stimulant laxatives are not an
acceptable alternative to a changed diet.
Interaction with other medicaments and other forms of		F
interaction. Hypokalaemia (resulting from long-term laxative

abuse) potentiates the action of cardiac glycosides and interacts with antiarrhythmic drugs and drugs which induce reversion to sinus rhythm (e.g. quinidine). Concomitant use with other drugs inducing hypokalaemia (e.g. thiazide diuretics, adrenocorticosteroids and liquorice root) may enhance electrolyte imbalance.

Pregnancy and lactation The use of stimulant laxatives, particularly unstandardised preparations, is not generally recommended during pregnancy (see Senna).

The EMEA HMPC Community Herbal Monograph for frangula includes the following information on use during pregnancy and lactation.

Pregnancy Frangula is not recommended during pregnancy.(1) There are no reports of undesirable or damaging effects

during pregnancy and on the foetus when used at the recommended dosage schedule. However, experimental data concerning a genotoxic risk of several anthranoids, e.g. emodin and physcion, and frangula extract are not counterbalanced by sufficient studies to eliminate a possible risk.(1)

Lactation Frangula is not recommended during breast feeding, as there are insufficient data on the excretion of its metabolites in breast milk. Excretion of the active principles of frangula in breast milk has not been investigated. However, small amounts of active metabolites (e.g. rhein) from other anthranoids are known to be excreted in breast milk. A laxative effect in breastfed babies has not been reported.(1)

Preparations

Proprietary single-ingredient preparations

France: Depuratif des Alpes. Switzerland: Elixir frangulae compositum.

Proprietary multi-ingredient preparations

Australia: Granocol; Normacol Plus. Austria: Artin; Gallesyn; Gallesyn; Laxalpin; Laxolind; Mag Kottas Krauterexpress Abfuhrtee; Mag Kottas May-Cur-Tee; Planta Lax; Waldheim Abfuhrdragees mild. Belgium: Grains de Vals; Normacol Plus. Canada: Constipation; Herbalax. Czech Republic: AbfuhrHeilkrautertee; Cholagol; Reduktan; The Salvat. Denmark: Ferroplex-frangula. France: Dragees Fuca; Dragees Vegetales Rex; Mediflor Tisane Antirhumatismale No 2; Mediflor Tisane Circulation du Sang No 12. Germany: Abdomilon. Hong Kong: Hepatofalk; Normacol Plus. Hungary: Cholagol. India: Kanormal. Ireland: Normacol Plus. Israel: Encypalmed; Rekiv. Italy: Draverex; Fave di Fuca; Lactolas; Neoform.

272 Frangula

Mexico: Normacol. Netherlands: Roteroblong Maagtabletten. New Zealand: Granocol; Normacol Plus. Portugal: Normacol Plus. South Africa: Normacol Plus. Singapore: Normacol Plus. Spain: Normacol Forte. Switzerland: Colosan plus; Lapidar 10; Linoforce; LinoMed; Padma-Lax; Padmed Laxan; Phyto-Laxia; Phytolaxin. UK: Herbulax; Lustys Herbalene; Natravene; Normacol Plus.

Reference

1European Medicines Agency. Committee on Herbal Medicinal Products. Community Herbal Monograph on Rhamnus frangula L., Cortex. London, 26 October 2006. Doc Ref. EMEA/HMPC/76307/ 2006

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