Boldo

Scientific Name(s): Peumus boldus Molina also referred to as Boldu boldus (Molina) Lyons and Boldea fragrans Gay. Family: Monimiaceae

Common Name(s): Boldo , boldus , boldoa , boldea

Uses

Boldo has been shown to possess cytoprotective and anti-inflammatory actions and to improve GI disorders; however, there is limited data to support these uses.

Dosing

Boldo extract was studied at a dose of 2.5 g daily for its effect on intestinal transit time. Classical use of boldo leaves was at a dose of 0.5 g.

Contraindications

Patients with kidney disorders, liver disease, gallstones, and other medical illnesses should not use this herbal.

Pregnancy/Lactation

Documented adverse effects from the irritant oil. Avoid use.

Interactions

Boldo ingestion may enhance the anticoagulant effect of warfarin, increasing the risk of bleeding. Patients taking warfarin should consult their health care provider before taking boldo or other herbal products.

Adverse Reactions

Boldo is known to be a CNS stimulant.

Toxicology

Serious health hazards exist with internal use. Patients with kidney disorders, liver disease, gallstones, and other medical illnesses should not use this herbal. Large doses cause paralysis and death.

Botany

Boldo is an evergreen shrub or small tree native to central Chile and Peru.

History

In Chile, the yellowish-green fruit is eaten, its bark used in tanning, and its wood used for charcoal. 1 Boldo leaves have been used by South American natives against diseases of the liver and for the treatment of gallstones. 2 The plant is used in homeopathy in the treatment of digestive disorders, as a laxative, choleretic (a stimulant of bile secretion), diuretic, 3 and for hepatic diseases. 1 The leaves also have been used for worms, urogenital inflammations (eg, gonorrhea, syphilis), gout, rheumatism, head colds, and earaches. 4 Boldo extract is used as a flavoring for alcoholic beverages. An ethnobotanical survey is available, demonstrating boldo's importance in Guatemalan culture as a medicinal plant. 5

Chemistry

Several studies report a number of alkaloids present in boldo. Older reports list constituents noraporphines, laurolitsine, 6 reticuline, isoboldine, 7 and others. Presence of alkaloid boldine has been confirmed by many reports. 8 , 9 , 10 , 11 Boldine content in leaves varies, with maximum amounts (0.29%) being reached in the summer. Another report finds boldine to be a minor alkaloid, comprising 8.5% to 18.6% total leaf alkaloids. Other boldine-associated alkaloids were identified as isoboldine, N-methyllaurotetanine, laurotetanine, isocorydine, and nor-isocorydine. 12 Other isoquinoline alkaloids from boldo have been determined, some of which include (-)-pronuciferine and sinoacutine. 13 , 14 Other reported alkaloids include 6a,7-dehydroboldine and (R)- and (S)-coclaurine from the bark of the plant. 15 , 16

Up to 46 compounds have been identified in the essential oil of boldo, with the main components being P-cymene, ascaridole, and 1,8-cineole. 17 , 18 Four major compounds in the essential oil, as reported in another study, include p-cymen-7-ol, transverbenol, thymol, and ascaridole. 19 Genetic variation of the essential oil, as well as alkaloid content, has been addressed. 20 Variability is dependent upon season, location, sex, canopy height, leaf age, and light intensity. 21 , 22

Tannic acid (20 to 40 mg/g) has been reported from boldo. 23

Other developments in boldo and boldine chemistry have been reported. 24 , 25

Uses and Pharmacology

GI disorders

Boldine and boldo extracts are known to exhibit choleretic properties, stimulating bile flow. 7 , 26

Animal data

Flavones boldoside and peumoside suppressed induced excitation in mice and demonstrated marked spasmolytic effect in rabbits experiencing gut spasm. 27 Boldine possesses cytoprotective and anti-inflammatory properties in experimental colitis models. 28

Clinical data

Dry boldo extract prolonged oro-cecal transit time when studied in 12 volunteers, explaining its medicinal use. 29 Boldo in combination with cascara has been used to treat constipation in the elderly. 30

Anti-inflammatory and antipyretic effects

Besides its beneficial actions in the GI tract, boldine was shown to exert anti-inflammatory and antipyretic effects as well. Boldine is an effective inhibitor of prostaglandin synthesis. 31

Animal data

Dried hydro-alcoholic extract of the plant reduced the inflammatory process in a carrageenan-induced edema test in rats. 32

Clinical data

Research reveals no clinical data regarding the use of boldo as an anti-inflammatory and antipyretic.

Cytoprotective

Boldine, in several reports, demonstrates cytoprotective and antioxidant actions. Boldine prevented free radical erythrocyte lysis in one report. 33

Animal data

The plant also has been evaluated for its ability to protect against liver damage in rat hepatocytes, in CCl 4 -induced toxicity in mice, 34 and in rat 34 and human liver microsomes. 35 Reduction of lethal effect in Escherichia coli submitted to reactive oxygen species was shown by treatment with boldine. 36 Boldine demonstrated protective effects against oxidative mitochondrial damage in rats. 37 A review of the antioxidative properties of boldo over the last 4 decades finds boldo to be an effective antioxidant in biological and nonbiological systems. 38

Clinical data

Research reveals no clinical data regarding the use of boldo as a cytoprotective.

Other uses

Essential oil of boldo has been shown to exhibit antimicrobial effects against a number of organisms, including Streptococcus pyogenes , Micrococcus sp., and Candida sp. 39

Other studies performed with boldo/boldine demonstrate neuromuscular blockade in mouse phrenic nerve-diaphragm, 40 sensitize ryanodine receptor and induce calcium release from storage sites in isolated skeletal muscle, 41 and absorb UV radiation, suggesting possible use as a sunscreen. 42 A patent has been granted regarding the use of boldo in cosmetic/dermatological products to prevent the aging process. 43 Boldo also has been studied in the radioactive labeling of blood cells and plasma proteins, tracing uptake by cells. 44 , 45

Dosage

Boldo extract was studied at a dose of 2.5 g daily for its effect on intestinal transit time. Classical use of boldo leaves was at a dose of 0.5 g. 29

Pregnancy/Lactation

Documented adverse effects from the irritant oil. 46 Avoid use.

Interactions

A 67-year-old woman receiving 2 mg daily of warfarin experienced an increase in anticoagulant parameters while taking natural products containing boldo after meals and fenugreek before meals. One week after the patient stopped taking boldo and fenugreek, anticoagulant measurements returned to the therapeutic range. Because the patient refused to stop taking the herbal products, it was necessary to decrease the dose of warfarin by 15% in order to maintain anticoagulant parameters in the therapeutic range. 47

Adverse Reactions

Research reveals little or no information regarding adverse reactions associated with boldo.

Toxicology

Oral doses of 0.5 mg/g killed mice, while doses of 15 g caused fatal intoxications in dogs. 2 Death was caused by respiratory depression. Physiologically, boldo stimulates the CNS, causing exaggerated reflexes, disturbed coordination, and convulsions. In large doses, boldo causes paralysis of the motor and sensory nerves and eventually the muscle fibers as well, causing death by respiratory arrest. 1

Reviews on boldine report low toxicity in animal studies, which does not imply safety for use in humans. 34 , 38 In certain animals/cell lines, mitotic recombinant events such as crossover and gene conversion were induced by boldine, as were weak mutations in yeast cells. 48 However, boldine tested in vitro for clastogenic effect in human lymphocytes, and administration of up to 900 mg/kg given to mice, did not cause any significant increase in frequency of chromosomal aberrations in another report. 49 Hydro-alcoholic extract of boldo and boldine demonstrated abortive and teratogenic actions in a later study. This report also found changes in blood levels of bilirubin, glucose, cholesterol, ALT, AST, and urea in rats. 50 Serious health hazards exist with internal use in humans. Many boldo products contain ascaridole; patients with kidney disorders, liver disease, gallstones, and other medical illnesses should not use this herbal.

Bibliography

1. Osol A, ed. The Dispensatory of the United States of America . 25th ed. Philadelphia, PA: Lippincott, 1955.
2. Genest K, et al. Can J Pharm Sci 1965;3:85.
3. DaLegnano L. The Medicinal Plants . Milan, Italy: Edizione Mediterranea, 1968.
4. Duke J. The Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press, 1985.
5. Giron L, et al. Ethnobotanical survey of the medicinal flora used by the Caribs of Guatemala. J Ethnopharmacol 1991;34(2-3):173-87.
6. Hughes D, et al. Alkaloids of Peumus boldus . Isolation of laurotetanine and laurolitsine. J Pharm Sci 1968;57(9):1619-20.
7. Hughes D, et al. Alkaloids of Peumus boldus . Isolation of (+)-reticuline and isoboldine. J Pharm Sci 1968;57(6):1023-25.
8. Di Renzo N. Densitometric determination of boldine in boldo extracts. Boll Chim Farm 1972;111(7):450-53.
9. Fleischmann L, et al. Densitometric determination of small quantity of boldin in Boldo extracts and in pharmaceutic preparations. Boll Chim Farm 1975;114(9):534-38.
10. Quercia V, et al. HPLC determination of boldine contents in boldus extracts. Boll Chim Farm 1978;117(9):545-48.
11. Windholz M, et al. The Merck Index , 10th ed. Rahway, NJ: Merck & Co., 1983.
12. Betts T. Chromatographic evaluation of boldine and associated alkaloids in boldo. J Chromatogr 1990;511:373-78.
13. Pietta P, et al. Determination of isoquinoline alkaloids from Peumus boldus by high performance liquid chromatography. J Chromatogr 1988;457:442-45.
154. Urzua A, et al. Alkaloids from the bark of Peumus boldus . Fitoterapia 1983;54(4):175-77.
15. Urzua A, et al. 6a,7-Dehydroboldine from the bark of Peumus boldus . J Nat Prod 1984;47(3):525-26.
16. Asencio M, et al. (R)- and (S)-coclaurine from the bark of Peumus boldus . Fitoterapia 1993;64(5):455-58.
17. Bruns K, et al. Composition of Peumus boldus leaf oil. Parfuem Kosmet 1974;55(8):225-27.
18. Miraldi E, et al. Peumus boldus essential oil: New constituents and comparison of oils from leaves of different origin. Fitoterapia 1996;67(3):227-30.
19. Sargenti S, et al. Supercritical fluid extraction of Peumus boldus . J High Resolut Chromatogr 1997;20(9):511-15.
20. Vogel H, et al. Studies of genetic variation of essential oil and alkaloid content in boldo ( Peumus boldus ). Planta Med 1999;65(1):90-91.
21. Vogel H, et al. Variability of some active compounds in boldo ( Peumus boldus Mol.). Zuechtungsforsch 1996;2(1):364-67.
22. Montes Guyot M, et al. Essential oil of the leaves of boldo ( Peumus boldus Mol.). Seasonal yield and variation. An R Acad Farm 1980;46(3):325-34.
23. Pizarro F, et al. Factors which modify the nutritional state of iron: tannin content of herbal teas. Arch Latinoam Nutr 1994;44(4):277-80.
24. Cassels B. Recent chemical and pharmacological studies concerning boldo and boldine. Bol Soc Quim Peru 1995;61(4):229-31.
25. Cassels B, et al. Recent developments in the chemistry and pharmacology of boldo and boldine. Chem, Biol Pharmacol Prop Med Plants Am Proc IOCD/CYTED Symp 1999, 197-206.
26. Salati R, et al. Evaluation of the choleretic property of 2 preparations containing extracts of boldo and cascara. Minerva Dietol Gastroenterol 1984;30(3):269-72.
27. Borkowski B, et al. Pharmacodynamic investigations on flavone derivatives from the leaves of Peumus boldus . Herba Pol 1965;11(3):198-93.
28. Gotteland M, et al. Protective effect of boldine in experimental colitis. Planta Med 1997;63(4)311-15.
29. Gotteland M, et al. Effect of a dry boldo extract on oro-cecal intestinal transit in healthy volunteers. Rev Med Chil 1995;123(8):955-60.
30. Marchesi M, et al. Clinical experience with a preparation containing cascara sagrada and boldo in the therapy of simple constipation in the elderly. G Clin Med 1982:63(11-12):850-63.
31. Backhouse N, et al. Anti-inflammatory and antipyretic effects of boldine. Agents Actions 1994;42(3-4):114-17.
32. Lanhers M, et al. Hepatoprotective and anti-inflammatory effects of a traditional medicinal plant of Chile, Peumus boldus . Planta Med 1991;57(2):110-15.
33. Jimenez I, et al. Protective effects of boldine against free radical-induced erythrocyte lysis. Phytother Res 2000;14(5):339-43.
34. Cederbaum A, et al. Inhibition of rat liver microsomal lipid peroxidation by boldine. Biochem Pharmacol 1992;44(9):1765-72.
35. Kringstein P, et al. Boldine prevents human liver microsomal lipid peroxidation and inactivation of cytochrome P4502E1. Free Radic Biol Med 1995;18(3):559-63.
36. Reininger I, et al. Boldine action against the stannous chloride effect. J Ethnopharmacol 1999;68(1-3):345-48.
37. Jang Y, et al. Protective effect of boldine on oxidative mitochondrial damage in streptozocin-induced diabetic rats. Pharmacol Res 2000;42(4):361-67.
38. Speisky H, et al. Boldo and boldine: an emerging case of natural drug development. Pharmacol Res 1994;29(1):1-12.
39. Vila R, et al. Composition and antimicrobial activity of the essential oil of Peumus boldus leaves. Planta Med 1999;65(2):178-79.
40. Kang J, et al. Studies on neuromuscular blockade by boldine in the mouse phrenic nerve-diaphragm. Jpn J Pharmacol 1998;76(2):207-12.
41. Kang J, et al. Effects of boldine on mouse diaphragm and sarcoplasmic reticulum vesicles isolated from skeletal muscle. Planta Med 1998;64(1):18-21.
42. Hidalgo M, et al. Boldine as a sunscreen: its photoprotector capacity against UVB radiation. Cosmet Toiletries 1998;113(9):59,60,62-64,66.
43. Pauley G. Use of a boldo extract in a cosmetic or dermatological product. German patent application #WO 99-EP7261.
44. Reiniger I, et al. Effect of Peumus boldus on the labeling of red blood cells and plasma proteins with technetium-99m. Appl Radiat Isot 1999;51(2):145-49.
45. Braga A, et al. The effect of drugs on the labeling of blood elements with technetium-99m. Curr Pharm Des 2000;6(11):1179-91.
46. Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals . London: Pharmaceutical Press; 1996.
47. Lambert JP, et al. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy . 2001;21:509-512.
48. Moreno P, et al. Genotoxicity of the boldine aporphine alkaloid in prokaryotic and eukaryotic organisms. Mutat Res 1991;260(2):145-52.
49. Tavares D, et al. Evaluation of the genotoxic potential of the alkaloid boldine in mammalian cell systems in vitro and in vivo. Mutat Res 1994;321(3):139-45.
50. Almeida D, et al. Toxicological evaluation of the hydro-alcohol extract of the dry leaves of Peumus boldus and boldine in rats. Phytother Res 2000;14(2):99-102.

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