Bogbean

Summary and Pharmaceutical Comment

The chemistry of bogbean is well studied, but no pharmacological information is available to justify the herbal uses. In view of the lack of toxicity data, excessive doses should be avoided.

Species (Family)

Menyanthes trifoliata L. (Menyanthaceae)

Synonym(s)

Buckbean, Marsh Trefoil, Menyanthes

Part(s) Used

Leaf

Pharmacopoeial and Other Monographs

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

Figure 1 Selected constituents of bogbean.

B

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G2, G62 and G64.

Acid Caffeic acid, chlorogenic acid, ferulic acid, p-hydroxyben- zoic acid, protocatechuic acid, salicylic acid, vanillic acid;(1, 2) folic acid and palmitic acid.(2)

Alkaloids Gentianin and gentianidine (pyridine-type); choline.(2)

Coumarins Scopoletin.(2)

Flavonoids Hyperin, kaempferol, quercetin, rutin and trifolio- side.(1, 2)

Iridoids 70,80-Dihydrofoliamenthin, foliamenthin, loganin, menthiafolin and sweroside.(2–4)

Other constituents Carotene, ceryl alcohol, enzymes (e.g. emulsin, invertin), a-spinasterol, an unidentified substance with haemolytic properties.(2) a-Spinasterol has been reported to be a mixture of five sterols with a-spinasterol and stigmast-7-enol as major components.(5)

Food Use

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

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

Herbal Use

Bogbean is stated to possess bitter and diuretic properties. It has been used for rheumatism, rheumatoid arthritis, and specifically

for muscular rheumatism associated with general asthenia.(G2, G7,

G8, G64)

Figure 2 Bogbean (Menyanthes trifoliata).

90 Bogbean

B

Figure 3 Bogbean – dried drug substance (leaf).

Dosage

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

Dried leaf 1–2 g or by infusion three times daily.(G7)

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

Tincture 1–3 mL (1 : 5 in 45% alcohol) three times daily.(G7)

Pharmacological Actions

In vitro and animal studies

A choleretic action has been described for caffeic acid and ferulic acid; a stomachic secretive action has been reported for protocatechuic acid and p-hydroxybenzoic acid. The iridoids possess bitter properties.(1) The bitter index (BI) of bogbean is stated to be 4000–10 000 (compared to gentian BI 10 000– 30 000).(G62) Bogbean extracts have antibacterial activities.(6, 7)

Side-effects, Toxicity

Large doses of bogbean are stated to be purgative and may cause vomiting.(8) An unidentified substance with haemolytic activity has been isolated from bogbean.(2)

Contra-indications, Warnings

Excessive doses may be irritant to the gastrointestinal tract, causing diarrhoea, griping pains, nausea and vomiting.(8)

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

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

Preparations

Proprietary single-ingredient preparations

Czech Republic: List Vachty Trojliste.

Proprietary multi-ingredient preparations

Austria: Mariazeller. Czech Republic: Naturland Grosser Swedenbitter. France: Tisane Hepatique de Hoerdt. Germany: Gallexier. Russia: Original Grosser Bittner Balsam (Ориги-

нальный Большой Бальзам Биттнера). UK: Modern Herbals Rheumatic Pain; Rheumatic Pain; Rheumatic Pain Relief; Rheumatic Pain Remedy; Rheumatic Pain Tablets; Sciatica Tablets; Vegetex.

References

1Swiatek L et al. Content of phenolic acids in leaves of Menyanthes trifoliata. Planta Med 1986; 52: 530.

2 Giaceri G. Chromatographic identification of coumarin derivatives in

Menyanthes trifoliata L. Fitoterapia 1972; 43: 134–138.

3Battersby AR et al. Seco-cyclopentane glucosides from Menyanthes trifoliata: foliamenthin, dihydrofoliamenthin, and menthiafolin. Chem

Commun 1968; 1277–1280.

4 Loew P et al. The structure and biosynthesis of foliamenthin. Chem Commun 1968; 1276–1277.

5Popov S. Sterols of the Gentianaceae family. Dokl Bolg Akad Nauk 1969; 22: 293–296.

6 Moskalenko SA. Preliminary screening of Far-Eastern ethnomedicinal plants for antibacterial activity. J Ethnopharmacol 1986; 15: 231–259.

7Bishop CJ, MacDonald RE. A survey of higher plants for antibacterial substances. Can J Bot 1951; 29: 260–269.

8Todd RG, ed. Martindale: The Extra Pharmacopoeia, 25th edn. London: Pharmaceutical Press, 1967.

Boldo

Summary and Pharmaceutical Comment

The chemistry of boldo is well documented, and some pharmacological data are available. Clinical studies have described choleretic activity, although further well-designed studies are required to establish this. The reputed diuretic and mild urinary antiseptic properties of boldo are probably attributable to the irritant volatile oil. In view of the toxicity

data and the irritant nature of the volatile oil, excessive and/or long-term use of boldo should be avoided.(G56)

Species (Family)

Peumus boldus Molina (Monimiaceae)

Synonym(s)

Boldi Folium, Boldus

Part(s) Used

Leaf

Pharmacopoeial and Other Monographs

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

ESCOP 1996(G52)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

WHO volume 1 1999(G63)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G2, G52 and G62.

Alkaloids Isoquinoline-type. 0.25–0.7%. Pharmacopoeial standard not less than 0.1% alkaloid calculated as boldine.(G81, G84)

Boldine 0.06% (major, disputed), isoboldine, 6a,7-dehydrobol- dine, isocorydine, isocorydine-N-oxide, norisocorydine, laurolitsine, laurotetanine, N-methyllaurotetanine (aporphines), reticuline; ( )-pronuciferine (proaporphine) and sinoacutine (morphinandienone).

Flavonoids Flavonols (e.g. isorhamnetin) and their glycosides.(5, 6)

Volatile oils 2.5%. Some 38 components have been identified, including p-cymene 28.6%, ascaridole 16.1%, 1,8-cineole 16.0%, linalool 9.1%, terpinen-4-o1 2.6%, a-terpineol 0.9%, fenchone 0.8% and terpinolene 0.4%.

Other constituents Coumarin 0.5%, resin and tannin.

B

Food Use

Boldo is listed by the Council of Europe as a natural source of food flavouring (category N3). This category indicates that boldo can be added to foodstuffs in the traditionally accepted manner, although insufficient information is available for an adequate

assessment of potential toxicity.(G16) Previously, in the USA, boldo was approved for food use in alcoholic beverages only.(G64)

Herbal Use

Boldo is stated to possess cholagogue, liver stimulant, sedative, diuretic, mild urinary demulcent, and antiseptic properties. It has been used for mild digestive disturbances, constipation, gallstones, pain in the liver or gall bladder, cystitis, rheumatism, and specifically for cholelithiasis with pain.(G2, G7, G64) The German Commission E approved use for treatment of dyspepsia and mild spastic gastrointestinal complaints.(G3)

Dosage

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

Figure 1 Selected constituents of boldo.

peroxidation in a rat liver preparation by 50%.(8) A dried aqueous ethanolic extract (0.06–0.115%) of boldine at a dose of 500 mg/kg gave 70% protection against carbon tetrachloride-induced hepa-

Figure 2 Boldo (Peumus boldus).

Figure 3 Boldo – dried drug substance (leaf).

totoxicity in mice, and boldine alone (10 mg/kg) gave 49% protection.(7) An aqueous ethanolic extract of boldo at doses of 50 and 100 mg/kg administered intraperitoneally showed anti-inflam- matory activity in the rat paw carrageenan-induced oedema test, whereas boldine alone appeared to be inactive.(7)

Boldine showed concentration-dependent relaxant activity on isolated rat ileum (EC50 1.7 10 4 mol/L), and acted as a competitive antagonist of acetylcholine and as a non-competitive antagonist of barium.(9) Boldine at low micromolar concentrations prevented oxidation in rat brain homogenate and lipid peroxidation of red cell plasma membranes, led to inactivation of lysozymes, indicating high reactivity of free radicals.(10)

Boldo essential oil contains terpinen-4-ol, the irritant and diuretic principle in juniper oil.

Clinical studies

Clinical investigation of the effects of boldo is extremely limited and rigorous randomized controlled clinical trials are required. In a controlled trial, boldo, in combination with cascara, rhubarb and gentian, had a beneficial effect on a variety of symptoms such

as loss of appetite, digestion difficulties, constipation, flatulence and itching.(11, 12) Rhubarb and gentian were found to be more

effective with respect to appetite-loss related symptoms, and boldo and cascara more effective in relieving constipation-related symptoms.

Two preparations containing extracts of boldo and cascara have been documented to increase biliary flow without altering the lithogenic index or bile composition.(13) Treatment of 12 human volunteers with boldo dry extract resulted in prolongation of intestinal transit time.(G4) However, the methodological limitations of this small, uncontrolled study do not allow any conclusions to be drawn on the effects of boldo.

Ascaridole, a component of the volatile oil, previously found a clinical use as an anthelmintic agent.(14) However, this use has declined with the development of synthetic compounds with lower toxicity and a wider range of activity.

Side-effects, Toxicity

Boldo volatile oil is stated to be one of the most toxic oils.(G58) Application of the undiluted oil to the hairless backs of mice has an irritant effect.(15) The oil contains irritant terpenes, including terpinen-4-ol, the irritant principle in juniper oil.

An acute oral LD50 value for boldo oil has been given as 0.13 g/ kg body weight in rats, with doses of 0.07 g/kg causing convulsions.(15) The acute dermal LD50 in rabbits has been reported as 0.625–1.25 g/kg.(15) No acute toxicity was observed in rats given oral doses of 3 g/kg of dry aqueous ethanolic extract, and in mice, an aqueous ethanolic extract (1 : 1) had an LD50 of 6 g/kg (intraperitoneal administration).(G52) The LD50 values of total alkaloids and of boldine in mice were 420 and 250 mg/kg (intraperitoneal administration), respectively.(G52) Total alkaloids (intraperitoneal administration) given to dogs produced vomiting,

diarrhoea and epileptic symptoms with a recovery after 50 minutes.(G52)

Boldine was not genotoxic as indicated by the SOS chromotest with Escherichia coli, or in the Ames test, and did not induce mutations in Saccharomyces cerevisiae.(16) Boldine did not induce an increase in the frequency of chromosome aberrations in human lymphocytes in vitro, or in mouse bone marrow cells in vivo. There were no signs of genotoxicity in mouse bone marrow, as assessed by the micro nucleus test.(16)

Contra-indications, Warnings

Excessive doses of boldo may cause renal irritation, because of the volatile oil, and should be avoided by individuals with an existing kidney disorder. Boldo is contra-indicated in individuals with obstruction of bile duct or severe liver disease. Boldo should only

be used in patients with gallstones after consultation with a physician.(G3) Ascaridole is toxic and use of the oil is not

recommended.(G58)

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

Pregnancy and lactation The safety of boldo taken during pregnancy has not been established. In view of the potential irritant nature of the volatile oil, the use of boldo during pregnancy should be avoided.

Preparations

Proprietary multi-ingredient preparations

Argentina: Biliosan Compuesto; Boldina; Dioxicolagol; Drenocol; Hepacur; Hepatalgina; Hepatodirectol; Metiogen; Opobyl; Radicura. Australia: Berberis Complex; Lexat. Austria: St Bonifatius-Tee. Brazil: Alcafelol; Alcaflor; Bilifel; Boldopeptan; Boljuprima; Colachofra; Ductoveran; Emagrevit; Eparema; Figatil; Gotas Digestivas; Hepatoregius; Jurubileno; Prinachol; Solvobil. Chile: Hepabil; Nature Complex ReductTe; Reduc-Te. Czech Republic: The Salvat. France: Bolcitol; Drainactil; Elixir Spark; Grains de Vals; Hepaclem; Hepax; Jecopeptol; Mediflor no 11 Draineur Renal et Digestif; Mediflor Tisane Hepatique No 5; Mucinum a l'Extrait de Cascara; Opobyl; Solution Stago Diluee; Tisane Hepatique de Hoerdt. Germany: Cynarzym N; Heumann Verdauungstee Solu-Lipar. Hong Kong: Mucinum Cascara. Italy: Amaro Medicinale; Caramelle alle Erbe Digestive; Coladren; Colax; Confetti Lassativi CM; Critichol; Digelax; Dis-Cinil Complex; Eparema-Levul; Eparema; Eupatol; Hepatos B12; Hepatos; Magisbile; Mepalax; Solvobil. Mexico: Chofabol; Hepedren

Tablets; Weight Loss Aid.

References

1 Urzúa A, Acuña P. Alkaloids from the bark of Peumus boldus. Fitoterapia 1983; 4: 175–177.

2 Urzúa A, Torres R. 6a,7-Dehydroboldine from the bark of Peumus boldus. J Nat Prod 1984; 47: 525–526.

3 Hughes DW et al. Alkaloids of Peumus boldus. Isolation of laurotetatine and laurolitsine. J Pharm Sci 1968; 57: 1619–1620.

4 Hughes DW et al. Alkaloids of Peumus boldus. Isolation of (þ)- reticuline and isoboldine. J Pharm Sci 1968; 57: 1023–1025.

5 Bombardelli E et al. A new flavonol glycoside from Peumus boldus.

Fitoterapia 1976; 46: 3–5.

6 Krug H, Borkowski B. Neue Flavonol-Glykoside aus den Blättern von Peumus boldus Molina. Pharmazie 1965; 20: 692–698.

7 Lanhers MC et al. Hepatoprotective and anti-inflammatory effects of a traditional medicinal plant of Chile, Pneumus boldo. Planta Med 1991; 57:110–115.

8 Cederbaum AI et al. Inhibition of rat liver microsomal lipid peroxidation by boldine. Biochem Pharmacol 1992; 44: 1765–1772.

9 Speisky H et al. Activity of boldine on rat ileum. Planta Med 1991; 57: 519–522.

10Speisky H et al. Antioxidant properties of the alkaloid boldine in systems undergoing lipid peroxidation and enzyme inactivation. Biochem Pharmacol 1991; 41: 1575–1581.

11Borgia M et al. Pharmacological activity of a herbs extract: A controlled clinical study. Curr Ther Res 1981; 29: 525–536.

12Borgia M et al. Studio policentrico doppio-cieco doppio-controllato sull'attività terapeutica di una nota associazione di erbe medicamentose. Clin Ter 1985; 114: 401–409.

13Salati R et al. Valutazione delle proprietà coleretiche di due preparati contenenti estratti di boldo e cascara. Minerva Dietol Gastroenterol 1984; 30: 269–272.

14Wagner H, Wolff P, eds. New Natural Products and Plant Drugs with Pharmacological, Biological or Therapeutical Activity. Berlin: Springer-Verlag, 1977.

15Boldo leaf oil. Food Chem Toxicol 1982; 20 (Suppl. Suppl.B): 643.

16Moreno PRH et al. Genotoxicity of the boldine aporphine alkaloid in prokaryotic and eukaryotic organisms. Mutat Res 1991; 260: 145–152.