Plantain

Summary and Pharmaceutical Comment

The constituents of plantain are well-documented and the reputed antihaemorrhagic properties may be attributable to the tannin constituents. In addition, bronchospastic activity has been documented in preclinical and preliminary clinical studies. The toxicity of plantain is reported to be low, but excessive ingestion should be avoided.

Species (Family)

Plantago major L. (Plantaginaceae)

Synonym(s)

Common Plantain, General Plantain, Greater Plantain, Plantago asiatica auct. eur. pro parte, non L.

Part(s) Used

Leaf

Pharmacopoeial and Other Monographs

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

Plantain is not included in the GSL.(G37)

PConstituents

The following is compiled from several sources, including General References G2, G40, G51 and G62.

Acids Benzoic acid, caffeic acid, chlorogenic acid, cinnamic acid, p-coumaric acid, ferulic acid, fumaric acid, gentisic acid, p- hydroxybenzoic acid, neochlorogenic acid, salicylic acid, syringic

Figure 1 Selected constituents of plantain.

Alkaloids Trace (unspecified),(3, 4) boschniakine and the methyl ester of boschniakinic acid(5)

Amino acids DL-a-Alanine, asparagine, L-histidine, DL-lysine, DL- leucine, serine and tryptophan.(6)

Carbohydrates L-Fructose, D-glucose, planteose, saccharose, stachyose, d-xylose, sorbitol, tyrosol, mucilage and gum.(7)

Flavonoids Apigenin, baicalein, scutellarein, baicalin, homoplantaginin, nepitrin, luteolin, hispidulin and plantagoside.(8–10)

Iridoids Aucubin, aucubin derivatives, plantarenaloside, aucuboside and melitoside.(5, 11, 12)

Tannins 4%. Unspecified.

Other constituents Choline, allantoin, invertin and emulsin (enzymes), fat 10–20%, resin, saponins, steroids(13) and thioglucoside.

Food Use

Plantain leaf is not used in foods. A related species, Plantago lanceolata L., is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that P. lanceolata can be added to foodstuffs in small quantities, with a possible limitation of an active constituent (as yet unspecified) in the final product.(G16) Previously, plantain has

been listed by the Food and Drugs Administration (FDA) as a Herb of Undefined Safety.(G22)

Herbal Use

Plantain is stated to possess diuretic and antihaemorrhagic properties. Traditionally, it has been used for cystitis with

haematuria, and specifically for haemorrhoids with bleeding

and irritation.(G2, G7, G42, G64)

Dosage

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

Dried leaf 2–4 g as an infusion three times daily.(G7)

Liquid extract 2–4 mL (1 : 1 in 25% alcohol) three times daily.(G7)

Tincture 2–4 mL (1 : 5 in 45% alcohol) three times daily.(G7)

Pharmacological Actions

In vitro and animal studies

An aqueous extract has been reported to possess bronchodilatory activity in guinea-pigs. It was more effective against acetylcholineinduced contraction, than towards constriction induced by histamine or serotonin.(14) The bronchodilatory activity of plantain in guinea-pigs has been reported to be less active and of shorter duration compared to salbutamol or atropine.(15)

Hypotensive activity in normotensive, anaesthetised dogs has been documented; 125 mg/kg extract was found to decrease arterial blood pressure by 20–40 mmHg.(16)

An aqueous extract, reported to contain flavonoids, saponins, steroids and alkaloids, was shown to possess anti-inflammatory activity in the rat using various models of inflammation, and a strengthening of capillary vessels has also been documented.(13) However, an extract was found to exhibit minimal (11%) inhibition of carrageenan-induced rat paw oedema.(17) Leaf extracts in hexane have shown potent wound-healing activity in rabbits; the effect was primarily attributed to C26–C30 alcohols present in the extract.(18) Both the anti-inflammatory and woundhealing activities of plantain have been attributed to the high content of chlorogenic and neochlorogenic acids.(2)

Aucubin and a haemolytic saponin fraction have exhibited antibiotic activity towards Micrococcus flavus and Staphylococcus aureus (aucubin only).(19) Antibacterial activity towards Bacillus subtilis has been documented for the fresh plant juice, which was also found to lack activity towards Gram-positive organisms and fungi.(20) A negative response to cytotoxic, antitumour and antiviral activity was also reported for the plant juice.(20)

A mild laxative action has been reported in mice administered

iridoid glycosides, including aucubin.(21) Plantain seed is sometimes used as a substitute for ispaghula (a bulk laxative).(G45)

Plantain has been documented to lower concentrations of total plasma lipids, cholesterol, b-lipoproteins and triglycerides in rabbits with experimental atherosclerosis.(22) Plantain has been

reported to be useful in lowering plasma cholesterol concentrations.(23)

A tonus-raising effect on isolated guinea-pig and rabbit uterus tissue has been documented for an aqueous extract.(24)

Aucubin has been stated to be the active principle responsible for a hepatoprotective effect documented for plantain.(25)

Clinical studies

Clinical research assessing the effects of plantain is limited and rigorous randomised clinical trials are required.

Figure 2 Plantain (Plantago major).

Plantain 475

Figure 3 Plantain – dried drug substance (leaf).

Plantain has been reported to be effective in the treatment of chronic bronchitis of a spastic or non-spastic nature.(14, 26, 27) A pronounced improvement in both subjective and objective

symptoms of the common cold following treatment with plantain has also been reported.(28) Plantain, in combination with

agrimony, German chamomile, peppermint and St. John's wort, has been documented to provide pain relief in patients with chronic gastroduodenitis.(29) Following treatment, previously diagnosed erosions and haemorrhagic mucous changes were stated to have disappeared. However, the methodological limitations of these studies preclude definitive conclusions.

Side-effects, Toxicity

Clinical data

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

Allergic contact dermatitis to plantain has been reported.(G51)

The green parts of the plant are thought to yield a mustard oil- P type of thioglucoside, which releases an irritant principle (isothiocyanate) upon enzymatic hydrolysis.(G51) The seed may

also cause sensitisation and dermatitis.

Preclinical data

Plantain is reported to be of low toxicity with LD50 values in the

rat documented as 1 g/kg (intraperitoneal injection) and greater than 4 g/kg (by mouth).(15)

Contra-indications, Warnings

Plantain may cause a contact allergic reaction; it induces the formation of IgE antibodies, which may cross-react to psyllium.(30) Excessive doses may exert a laxative effect and a hypotensive effect.

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

Pregnancy and lactation In vitro uterotonic activity has been documented for plantain. In view of this, and the lack of information on safety, use of plantain should be avoided during pregnancy and lactation.

Summary and Pharmaceutical Comment

The chemistry of pleurisy root is poorly documented, but phytochemical studies on pleurisy root and related Asclepias species have identified many cardiac glycoside constituents. No scientific evidence was found to justify the herbal uses. There is a lack of clinical research assessing the efficacy and safety of pleurisy root. In view of the potential toxicity of pleurisy root, excessive use and use during pregnancy and lactation should be avoided.

Species (Family)

Asclepias tuberosa L. (Asclepiadaceae)

Synonym(s)

Asclepias, Butterfly Weed

Part(s) Used

Root

Pharmacopoeial and Other Monographs

BHP 1983(G7)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

GSL(G37)

Constituents

Little chemical information is available for pleurisy root. Cardiac glycosides of the cardenolide type (e.g. afroside, asclepin, calactin, calotropin, gomphoside, syriogenin, syrioside, uscharidin, uscharin and uzarigenin) have been documented for many Asclepias species,(1–4) including A. tuberosa.(5) Concentrations of cardiac glycosides are reported to vary between Asclepias species(1) and individual plant parts,(4) in descending order of latex, stem, leaf and root.(6)

No other data regarding constituents of the root were located.

Other plant parts Constituents documented for the herb include flavonols (e.g. kaempferol and quercetin) and flavonol glycosides (e.g. rutin and isorhamnetin), amino acids, caffeic acid, chlorogenic acid, choline, carbohydrates (e.g. glucose, fructose and sucrose), b-sitosterol, triterpenes (e.g. a-amyrin and b- amyrin, lupeol, friedelin, viburnitol), volatile oil and resin.(7, 8, G48)

Food Use

Pleurisy root is not used in foods.

Herbal Use

Pleurisy root is stated to possess diaphoretic, expectorant, antispasmodic and carminative properties. It has been used for

bronchitis, pneumonitis, influenza, and specifically for pleuri-

sy.(G7, G42, G64)

Dosage

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

Figure 1 Selected constituents of pleurisy root.

Dried root 1–4 g as an infusion three times daily.(G7)

Liquid extract 1–4 mL (1:1 in 45% alcohol) three times daily.(G7)

Tincture 1–5 mL (1 : 10 in 45% alcohol) three times daily.(G7)

Pharmacological Actions

In vitro and animal studies

Low doses of extracts of Asclepias species including A. tuberosa have been documented to cause uterine contractions (in vivo) and to exhibit oestrogenic effects.(5, 9, 10, G30) No effect was observed on blood pressure or respiration (in vivo), or on the isolated heart (frog, turtle).(9)

Figure 2 Pleurisy root (Asclepias tuberosa).

478 Pleurisy Root

Figure 3 Pleurisy root – dried drug substance (root).

reported for asclepin (Asclepias curassavica), which was found to be more potent, longer acting and with a wider safety margin when compared with other cardiac glycosides (including digoxin).(11–13) Asclepin was also reported to exhibit a more powerful activity towards weak cardiac muscle.(13) Plant extracts of A. curassavica,

Asclepias engelmanniana and Asclepias glaucescens have exhibited a stimulatory effect on the mammalian CNS, causing an increase in serotonin and noradrenaline concentrations.(14) Antitumour/cytotoxic activities have been documented for A. albicans and were attributed to various cardenolide constituents.(15)

Clinical studies

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

Side-effects, Toxicity

Clinical data

PThere is a lack of clinical safety and toxicity data for pleurisy root and further investigation of these aspects is required.

Pleurisy root and other Asclepias species have been documented to cause dermatitis; the milky latex is reported to be irritant.(G51)

Large doses may cause nausea, vomiting and diarrhoea.(G7, G42)

Preclinical data

Various Asclepias species, including A. tuberosa, are known to be toxic to livestock, with cardenolides implicated as the toxic constituents.(1, 5) Toxic effects on the lungs, gastrointestinal tract, kidneys, brain and spinal cord have been observed in rats and

rabbits following intravenous administration of an alcoholic extract.(10)

Toxicity studies involving related Asclepias species have also been documented. The cardenolide fraction of Asclepias eriocarpa is reported to contain toxic principles. The whole plant, plant extracts, an isolated and purified cardenolide (labriformin) and digoxin were all found to show qualitatively similar signs of toxicity and gross pathology in sheep and guinea-pigs.(16) LD50 values (mice, intraperitoneal injection) for cardenolides obtained from A. curassavica and A. eriocarpa were all estimated at less than 50 mg/kg body weight. Asclepin (A. curassavica) was reported to be safe following a three-month toxicity study in rats, using doses of 0.8, 8 and 20 mg/kg (route unspecified).(13) Asclepin has also been documented to have a wider margin of safety than digoxin(11–13) (see In vitro and animal studies).

Studies in cats have reported asclepin to be less cumulative compared to digoxin.(13)

Contra-indications, Warnings

Drug interactions None documented. However, the potential for preparations of pleurisy root to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. Cardiac glycosides (see Constituents) have been documented as constituents of pleurisy root.

Pregnancy and lactation Uterotonic activity (in vivo) has been reported for pleurisy root.(5, G30) In view of this and the potential

toxicity of pleurisy root, it should be avoided during pregnancy or lactation.

Preparations

Proprietary multi-ingredient preparations

Australia: Broncafect; Verbascum Complex. UK: Antibron; Chest Mixture; Horehound and Aniseed Cough Mixture; Vegetable Cough Remover.

References

1Seiber JN et al. New cardiac glycosides (cardenolides) from Asclepias species. Proceedings of the Australia/USA Poisonous Plants

Symposium. Plant Toxicol 1985: 427–437.

2Radford DJ et al. Naturally occurring cardiac glycosides. Med J Aust 1986; 144: P540–544.

3 Jolad SD et al. Cardenolides and a lignan from Asclepias subulata. Phytochemistry 1986; 25: 2581–2590.

4 Seiber JN et al. Cardenolides in the latex and leaves of seven Asclepias species and Calotropis procera. Phytochemistry 1982; 21: 2343–2348.

5 Conway GA, Slocumb JC. Plants used as abortifacients and emmenagogues by Spanish New Mexicans. J Ethnopharmacol 1979; 1: 241–261.

6 Duffey SS, Scudder GGE. Cardiac glycosides in North American Asclepiadaceae, a basis for unpalatability in brightly coloured Hemiptera and Coleoptera. J Insect Physiol 1972; 18: 63–78.

7Nelson CJ et al. Seasonal and intraplant variation of cardenolide content in the California milkweed Asclepias eriocarpa and

implications for plant defense. J Chem Ecol 1981; 7: 981–1010.

8Pagani F. Plant constituents of Asclepias tuberosa (Asclepiadaceae). Boll Chim Farm 1975; 114: 450–456.

9Costello CH, Butler CL. The estrogenic and uterine-stimulating activity of Asclepias tuberosa. J Am Pharm Assoc Sci Educ 1949; 39: 233–237.

10Hassan WE, Reed HL. Studies on species of Asclepias VI. Toxicology, pathology and pharmacology. J Am Pharm Assoc Sci Educ 1952; 41: 298–300.

11Patnaik GK, Dhawan BN. Pharmacological investigations on asclepin

– a new cardenolide from Asclepius curassavica. Part I. Cardiotonic activity and acute toxicity. Arzneimittelforschung 1978; 28: 1095–1099.

12Patnaik GK, Koehler E. Comparative studies on the inotropic and toxic effects of asclepin, g-strophanthin, digoxin and digitoxin.

Arzneimittelforschung 1978; 28: 1368–1372.

13Dhawan BN, Patnaik GK. Investigation on some new cardioactive glycosides. Indian Drugs 1985; 22: 285–290.

14Del Pilar Alvarez Pellitero M. Pharmacological action of medicinal plants in the nervous system. An Inst Farmacol Espan 1971; 20: 299–387.

15Koike K et al. Potential anticancer agents. V. Cardiac glycosides of

Asclepias albicans (Asclepiadaceae). Chem Pharm Bull 1980; 28: 401– 405.

16Benson JM et al. Comparative toxicology of cardiac glycosides from the milkweed Asclepias eriocarpa. Toxicol Appl Pharmacol 1977; 41: 131–132.