Peumus boldus / Boldo

n 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

Boldo 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.

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