Elder

Summary and Pharmaceutical Comment

Phytochemical details have been documented for elder, with flavonoids and triterpenes representing the main biologically active constituents. Anti-inflammatory, antiviral and diuretic effects have been observed in in vivo studies, thus supporting the herbal uses of elder. No documented studies in humans were found. Potentially toxic compounds have been reported for the bark (lectins) and the leaves (cyanogenetic glycosides); the flowers are suitable for use as a herbal remedy.

Species (Family)

Sambucus nigra L. (Caprifoliaceae)

Synonym(s)

Black Elder, European Elder, Sambucus

Sambucus canadensis L. refers to American Elder

Part(s) Used

Flower

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G6, G41, G62 and G75.

Flavonoids Flavonols (kaempferol, quercetin), quercetin glycosides (1.5–3.0%) including hyperoside, isoquercitrin and rutin.

Triterpenes a- and b-amyrin, oleanolic and ursolic acids.

Volatile oils 0.3%. 66% fatty acids (primarily linoleic, linolenic and palmitic) and 7% alkanes (C19, C21, C23 and C25). Numerous other constituent types have been identified including ethers and oxides, ketones, aldehydes, alcohols and esters.(1)

Other constituents Chlorogenic acid, tannin, mucilage, plastocynin (protein),(2) pectin and sugar.

Other plant parts Leaf Sambunigrin (0.042%), prunasin, zierin and holocalin (cyanogenetic glycosides),(3) choline, flavonoids (rutin, quercetin), sterols (sitosterol, stigmasterol, campesterol), triterpenes (a- and b-amyrin palmitates, oleanolic and ursolic acids), alkanes, fatty acids, tannins and others.(G41)

Bark Lectin (mol. wt 140 000) rich in asparagine/aspartic acid, glutamine/glutamic acid, valine and leucine,(4) phytohaemagglutinin,(5) triterpenoids (a-amyrenone, a-amyrin, betulin,

oleanolic acid, b-sito sterol).(6)

E

Food Use

Elder is listed by the Council of Europe as a source of natural food flavouring (categories N1 and N2). Category N1 refers to the fruit and indicates that there are no restrictions on quantities used. Category N2 refers to the restrictions on the concentrations of hydrocyanic acid that are permitted, namely 1 mg/kg in beverages and foods, 1 mg/kg for every per cent proof of alcoholic beverages, 5 mg/kg in stone fruit juices, 25 mg/kg in confectionery and 50 mg/

kg in marzipan.(G16) Previously, the flowers have had a regulatory status of GRAS (Generally Recognised As Safe).(G41)

Herbal Use

Elder is stated to possess diaphoretic and anticatarrhal properties. Traditionally, it has been used for influenza, colds, chronic nasal catarrh with deafness and sinusitis.(G8) Elder is also stated to act

as a diuretic, laxative and local anti-inflammatory agent.(G2, G6–

8, G41, G49, G64)

Dosage

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

Dried flower 2–4 g by infusion three times daily.(G6, G7)

Liquid extract 2–4 mL (1 : 1 in 25% alcohol) three times

daily.(G6, G7)

Figure 1 Selected constituents of elder.

238 Elder

Pharmacological Actions

In vitro and animal studies

Elder is stated to possess diuretic and laxative properties.(G41) Moderate (27%) anti-inflammatory action in carrageenan-

induced rat paw oedema has been documented for an elder preparation given one hour before carrageenan (100 mg/kg, by mouth).(7) Indometacin as a control exhibited 45% inhibition at a dose of 5 mg/kg.(7)

An infusion made from the flowers of elder, St John's wort herb

Eand root of soapwort (Saponaria officinalis) has exhibited antiviral activity against influenza types A and B (in vivo and in vitro) and herpes simplex virus type 1 (in vitro).(8)

A diuretic effect in rats exceeding that exerted by theophylline has been reported for elder.(9) An infusion and extracts rich in potassium and in flavonoids all caused diuresis. Greatest activity was exerted by the combined potassiumand flavonoid-rich extracts.

In vitro antispasmodic activity (rat ileum, rabbit/guinea-pig

intestine) and spasmogenic activity (rat uterus) have been reported for lectins isolated from elder.(10)

A lectin isolated from elder bark was found to be a lactose-

specific haemagglutinin with a slightly higher affinity for erythrocytes from blood group A.(4) Unlike many other plant lectins, the lectin did not inhibit protein synthesis.(4) The

carbohydrate-binding properties of a lectin isolated from elder bark have been studied.(11)

Phytohaemagglutinins are biologically active extracts isolated from various plants and represent a class of lectin. They are associated with haemagglutination and mitogenic, antigenic and immunosuppressant properties.(5) In vitro, phytohaemagglutinin has been found to stimulate production of an interferon-like substance in human leukocytes.(G45)

Hepatoprotective activity against carbon tetrachloride-induced toxicity has been reported for triterpenes isolated from Sambucus formosana Nakai.(12)

Clinical studies

There is a lack of clinical research assessing the effects of elder and rigorous randomised controlled clinical trials are required. Phytohaemagglutinin extracts have been used clinically to treat drug-induced leucopenia and some types of anaemia.(5) The blastogenic response of lymphocytes to phytohaemagglutinin has been used extensively as a measure of immunocompetence.(G45)

Side-effects, Toxicity

No reported side-effects specifically for elder were located. However, there is a lack of clinical safety and toxicity data for elder and further investigation of these aspects is required. Human poisoning has occurred with Sambucus species.(13) The roots, stems and leaves and, much less so, the flowers and unripe berries, are stated to contain a poisonous alkaloid and cyanogenic

glycoside causing nausea, vomiting and diarrhoea.(13) The flowers and ripe fruit are stated to be edible without harm.(13)

The effects of a lectin isolated from elder bark on mammalian embryonic and fetal development has been studied.(5) The lectin exerted mainly a toxic effect and, to a lesser degree, a teratogenic effect when administered subcutaneously to pregnant mice. In view of the high doses administered, the authors stated that the results did not indicate a potential hazard to human fetuses exposed to lectins.(5)

Contra-indications, Warnings

Plant parts other than the flowers are reported to be poisonous and should not be ingested. There is limited evidence from preclinical studies that elder has a diuretic effect; the clinical relevance of this, if any, is unclear.

Drug interactions None documented. However, the potential for preparations of elder to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered.

Pregnancy and lactation The safety of elder taken during pregnancy has not been established. In view of the lack of toxicity data, the use of elder during pregnancy and lactation should be avoided.

Preparations

Proprietary single-ingredient preparations

Czech Republic: Caj z Kvetu Bezu Cerneho; Kvet Bazy Ciernej. Russia: Novo-Passit (Ново-Пассит).

Proprietary multi-ingredient preparations

Australia: Sambucus Complex. Austria: Entschlackender Abfuhrtee EF-EM-ES; Grippetee St Severin; Krauter Hustensaft; Laxalpin; Sinupret; Tuscalman. Canada: Original Herb Cough Drops. Czech Republic: Biotussil; Cajova Smes pri Nachlazeni; Detsky Caj s Hermankem; Erkaltungstee; NovoPassit; Perospir; Pulmoran; Reduktan; Sinupret; Species Urologicae Planta; Urcyston Planta. Germany: Sinupret; Solvopret. Hong Kong: Sinupret. Hungary: Sinupret. Russia: Sinupret (Синупрет). Singapore: Sinupret. Spain: Natusor Gripotul; Natusor Sinulan. Switzerland: Sinupret; Tisane contre les refroidissements. Thailand: Sinupret. UK: Cleansing Herbs; EP&C Essence; Hay Fever & Sinus Relief; Hayfever & Sinus Relief; Herb and Honey Cough Elixir; Life Drops; Lion Cleansing Herbs; Lustys Herbalene; Modern Herbals Cold & Catarrh; Sinotar; Summertime Tea Blend; Tabritis; Tabritis Tablets. USA: Liquid Elderberry with Ester-C.

References

1Toulemonde B, Richard HMJ. Volatile constituents of dry elder (Sambucus nigra L.) flowers. J Agric Food Chem 1983; 31: 365–370.

Elder 239

2Scawen MD et al. The amino-acid sequence of plastocyanin from Sambucus nigra L. (elder). Eur J Biochem 1974; 44: 299–303.

3Jensen SR, Nielsen BJ. Cyanogenic glucosides in Sambucus nigra L. Acta Chem Scand 1973; 27: 2661–2685.

4Broekaert WF et al. A lectin from elder (Sambucus nigra L.) bark. Biochem J 1984; 221: 163–169.

8Serkedjieva J et al. Antiviral activity of the infusion (SHS-174) from flowers of Sambucus nigra L., aerial parts of Hypericum perforatum

L., and roots of Saponaria officinalis L. against influenza and herpes simplex viruses. Phytother Res 1990; 4: 97.

9Rebuelta M et al. Étude de l'effet diurétique de différentes préparations des fleurs du Sambucus nigra L. Plant Méd Phytothér

1983; 17: 173–181.

10Richter A. Changes in the motor activity of smooth muscles of the rat uterus in vitro as the effect of phytohaemagglutinins from Sambucus nigra. Folia Biol 1973; 21: 33–48.

11Shibuya N et al. The elderberry (Sambucus nigra L.) bark lectin recognizes the Neu5Ac(a2–6)Gal/GalNAc sequence. J Biol Chem 1987; 262: 1596–1601.

12Lin C-N, Tome W-P. Antihepatotoxic principles of Sambucus formosana. Planta Med 1988; 54: 223–224.

13Hardin JW, Arena JM, eds. Human Poisoning from Native and Cultivated Plants, 2nd edn. North Carolina: Duke University Press, 1974.

Summary and Pharmaceutical Comment

The pharmacological actions documented for elecampane seem to be attributable to the sesquiterpene lactone

Econstituents, in particular alantolactone and isoalantolactone. The demulcent action of mucilage and reported in vivo antispasmodic activity of the volatile oil support the traditional uses of this remedy in coughs. In addition, alantolactone has been utilised as an anthelmintic. A number of interesting cardiovascular activities have been documented for a related species, I. racemosa. Whether the constituents responsible for these actions are also present in elecampane is unclear. In view of the paucity of toxicity data for elecampane, excessive or prolonged use should be avoided.

Species (Family)

Inula helenium L. (Asteraceae/Compositae)

Synonym(s)

Alant, Horseheal, Inula, Scabwort, Tu Mu Xiang, Yellow Starwort

An elecampane extract has been referred to as helenin.

Alantolactone is also known as elecampane camphor, alant camphor, helenin and inula camphor.(G45)

Part(s) Used

Rhizome, root

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G2, G6 and G75.

Carbohydrates Inulin (up to 44%), mucilage.

Terpenoids b- and g-sitosterols, stigmasterol and damaradienol (sterols), friedelin.

Volatile oils 1–4%. Mainly contains sesquiterpene lactones including alantolactone, isoalantolactone and dihydroalantolactone (eudesmanolides), alantic acid and azulene.

Other constituents Resin.

Food Use

Elecampane is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that elecampane can be added to foodstuffs in small quantities, with a

possible limitation of an active principle (as yet unspecified) in the final product.(G16)

Previously in the USA, elecampane was only approved for use in alcoholic beverages.(G41)

Herbal Use

Elecampane is stated to possess expectorant, antitussive, diaphoretic and bactericidal properties. Traditionally, it has been used for bronchial/tracheal catarrh, cough associated with

pulmonary tuberculosis and dry irritating cough in children.(G2,

G6, G7, G8, G64)

Alantolactone has been used as an anthelmintic in the

treatment of roundworm, threadworm, hookworm and whipworm infection.(G44, G45)

Dosage

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

Rhizome/root 1.5–4.0 g as a decoction three times daily.(G6, G7)

Liquid extract 1.5–4.0 mL (1 : 1 in 25% alcohol) three times

daily.(G6, G7)

Pharmacological Actions

In vitro and animal studies

Elecampane infusion has exhibited a pronounced sedative effect in mice.(G41) Alantolactone has been reported to exhibit hypotensive, hyperglycaemic (large doses) and hypoglycaemic (smaller doses) actions in animals.(G41) Antibacterial properties have also been documented. Alantolactone and isoalantolactone have been

reported to exhibit high bactericidal and fungicidal properties in vitro.(G41)

The volatile oil has been reported to exert a potent smooth muscle relaxant effect in vitro on guinea-pig ileal and tracheal muscle.(1)

Various activities have been documented for Inula racemosa: an extract lowered plasma insulin and glucose concentrations in rats 75 minutes after oral administration,(2) counteracted adrenalineinduced hyperglycaemia in rats,(2) exhibited negative inotropic and chronotropic effects on the frog heart,(2) and provided a preventative and curative action against experimentally induced myocardial infarction in rats.(3) Pretreatment was found to be most effective.(3)

Sesquiterpene lactones with antitumour activity have been isolated from Helenium microcephalum.(4, 5)

Clinical studies

There is a lack of rigorous clinical research assessing the effects of elecampane and rigorous randomised controlled clinical trials are required.

Alantolactone has been used as an anthelmintic in the

treatment of roundworm, threadworm, hookworm and whipworm infection.(G44, G45)

Figure 1 Selected constituents of elecampane.

Inula racemosa has been reported to prevent ST-segment depression and T-wave inversion in patients with proven ischaemic heart disease,(2) and to have a beneficial effect on angina pectoris.(6)

Side-effects, Toxicity

There is a lack of clinical safety and toxicity data for elecampane and further investigation of these aspects is required.

Elecampane has been reported to cause allergic contact

dermatitis.(G51) Sensitising properties have been documented for the volatile oil,(G51, G58) and for alantolactone and isoalantolac-

tone.(7) In vitro cytotoxicty has been reported for alantolactone and isoalantolactone.(8)

Contraindications, Warnings

Elecampane may cause an allergic reaction, particularly in individuals with an existing allergy or sensitivity to other plants in the Asteraceae family.

Drug interactions None documented. However, the potential for preparations of elecampane to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. There is limited evidence from preclinical studies that alantolactone, a constituent of elecampane, has hypotensive and hypoand hyperglycaemic activities.

242 Elecampane

E

Figure 2 Elecampane (Inula helenium).

Figure 3 Elecampane – dried drug substance (rhizome).

Pregnancy and lactation The safety of elecampane taken during pregnancy has not been established. In view of the lack of toxicity data, the use of elecampane during pregnancy and lactation should be avoided.

Preparations

Proprietary multi-ingredient preparations

Austria: Brustund Hustentee St Severin. Czech Republic: Species Cholagogae Planta. France: Mediflor Tisane Digestive No 3; Mediflor Tisane Hepatique No 5. Germany: Klosterfrau Melisana. Russia: Original Grosser Bittner Balsam (Ориги-

нальный Большой Бальзам Биттнера). South Africa: Wonderkroonessens. Spain: Bronpul; Natusor Asmaten; Natusor Broncopul. Switzerland: Hederix; Padmed Laxan. UK: Cat- arrh-eeze; Cough-eeze; Horehound and Aniseed Cough Mixture; Vegetable Cough Remover.

References

1Reiter M, Brandt W. Relaxant effects on tracheal and ileal smooth muscles of the guinea pig. Arzneimittelforschung 1985; 35: 408–414.

2 Tripathi YB et al. Assessment of the adrenergic beta-blocking activity of Inula racemosa. J Ethno pharmacol 1988; 23: 3–9.

3 Patel V et al. Effect of indigenous drug (puskarmula) on experimentally induced myocardial infarction in rats. Act Nerv Super (Praha) 1982; (Suppl 3): 387–394.

4Sims D et al. Antitumor agents 37. The isolation and structural elucidation of isohelenol, a new antileukemic sesquiterpene lactone,

and isohelenalin from Helenium microcephalum. J Nat Prod 1979; 42: 282–286.

5Imakura Y et al. Antitumor agents XXXVI: Structural elucidation of sesquiterpene lactones microhelenins-A, B, and C, microlenin acetate, and plenolin from Helenium microcephalum. J Pharm Sci 1980; 69:

1044–1049.

6 Tripathi SN et al. Beneficial effect of Inula racemosa (pushkarmoola) in angina pectoris: a preliminary report. Indian J Physiol Pharmacol 1984; 28: 73–75.

7Stampf JL et al. The sensitising capacity of helenin and two of its main constituents the sesquiterpene lactones alantolactone and isoalantolactone: a comparison of epicutaneous and intradermal

sensitising methods in different strains of guinea pig. Contact Dermatitis 1982; 8: 16–24.

8Woerdenbag HJ. In vitro cytotoxicity of sesquiterpene lactones from Eupatorium cannabinum L. and semi-synthetic derivatives from eupatoriopicrin. Phytother Res 1988; 2: 109–114.