HERBAL
MEDICINAL
PLANT
BOLDO
Peumus boldus Molina (Monimiaceae) +
BY
RETTODWIKART THENU
BOLDO
(bole’doe)
Peumus boldus Molina (Monimiaceae) +
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)
OTHER COMMON NAMES
Boldea, boldine,
boldo-do-Chile, boldus
DESCRIPTION
MEDICINAL PARTS: The medicinal
parts are the leaves.
FLOWER AND FRUIT: The
inflorescences are racemes of whitish or pinkish campanulate flowers. The
berries are small, yellowish-green and edible.
LEAVES, STEM AND ROOT: The plant is a
strongly aromatic, heavily branched evergreen shrub 5 to 6 m tall. The leaves are
sessile, opposite, oval, about 5 cm long with an entire and slightly revolute
margin. They are rather thick and coriaceous with a protruding midrib and a row
of small glands on the upper surface. Both surfaces are slightly pubescent.
CHARACTERISTICS: Boldo has a
bitter, aromatic odor and a camphoraceous, lemony taste.
HABITAT: The plant is
indigenous to Chile and Peru. It is naturalized in mountainous Mediterranean
regions and on the western coast of the U.S.
PRODUCTION: Boldo leaf consists
of the dried leaves of Peumus boldius.
OTHER NAMES: Boldu, Boldus
SPECIES (FAMILY)
Boldea
boldus, Peumus boldus Molina (Monimiaceae)
SYNONYM(S)
Boldi Folium, Boldus
Boldea fragrans (Ruiz & Pav.) Gay, Peumus
fragrans Ruiz & Pav.
ORIGIN
Boldo is an evergreen found in
Chile, Peru, and Morocco.
PHARMACOPODIAL 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-dehydroboldine, isocorydine, isocorydine-N-oxide,
norisocorydine, laurolitsine, laurotetanine, N-methyllaurotetanine
(aporphines), reticuline; (_)-pronuciferine (proaporphine) and sinoacutine (morphinandienone).(1–4)
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.
COMPOUNDS
Isoquinoline
alkaloids of the aporphine type (0.25-0.5%): main alkaloid boldine (0.1%)
Volatile oil
(2-39c): chief
components are p-cymene, cineol, ascaridiole
Flavonoids: including rhamnetin-3-0-arabinoside-3'-0-
rhamnoside (peumoside), isorhamnetin-3-0-glucoside-7-0- rhamnoside (boldoside),
isorhamnetin dirhamnoside (fragroside)
USES
USES
Boldo is used as a laxative, liver tonic, and sedative.
It is also used to treat spastic conditions of the gastrointestinal tract, fl
atulence, gout, dysmenorrhea, colds, and weakness.
INVESTIGATIONAL
USES
Research is ongoing into the use of boldo as a
treatment for gallstones.
FOOD USEs
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)
Figure 1. Boldo (Peumus boldus).
Figure 2. Boldo – dried drug substance (leaf).
ACTIONS
Although boldo has been used to treat various
conditions in many parts of the world, its actions are not well researched.
Boldo is thought to possess diuretic, anthelmintic, and hepatoprotective
actions. The tannins are responsible for wound healing and antiinfl ammatory
actions. However, very little primary research is available to confirm these
actions.
Diuretic Action
Boldo
has been shown to possess diuretic effects. In a study of dogs given boldo, urine
excretion increased by 50% (Speisky et al, 1994).
Anthelmintic Action
One
of the chemical components of boldo, the volatile oil, ascaridole, exhibits anthelmintic
activity.
Other Actions
Boldo
may exert antioxidant, hepatoprotective, and antiinfl ammatory activity.
However, little research currently exists to confi rm these possible actions.
Boldo has shown uterine stimulant effects and teratogenic effects in rats
(Almedia, 2000). Only one study (Lanhers et al, 1991) could be found to confi
rm these effects. This study used an in
vitro technique in mice. Boldine, the main alkaloid, appears to possess a hepatoprotective
action but does not possess antiinfl ammatory action.
PHARMACOLOGICAL ACTIONS
IN VITRO AND ANIMAL STUDIES
Boldo has exhibited choleretic (highest activity in rats),
diuretic, stomachic and cholagogic properties.(G41, G52) The choleretic activity
may be due to synergy between flavonoids and alkaloids.(G52) Experiments in rats
have failed to demonstrate choleretic activity after oral administration of 400
or 800 mg/kg aqueous ethanolic extract, intraduodenal administration of 200 mg
or 800 mg/kg, and intravenous administration of 32.5– 130 mg/kg of a dry
ethanolic extract.(7)
An aqueous ethanolic extract (equivalent to 0.5–1.0 mg/mL dried
ethanolic extract) and also boldine (33 mg/mL) gave significant
hepatoprotection against t-butyl hydroperoxideinduced hepatotoxicity in rat
hepatocytes in vitro.(7) Boldine at a concentration of 0.015 mol/L inhibited
microsomal lipid 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 hepatotoxicity 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-inflammatory 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.
ACTIVITIES
Analgesic
(f; BGB; CRC); Anticholinergic (1; BRU); Antiinflammatory (1; APA); Antioxidant
(1; APA; BGB); Antirheumatic (f; EFS); Antiseptic (1; CAN; CRC; EFS); Antispasmodic
(2; APA; BRU; KOM; PH2; SHT); Aperitif (2; PHR); Carcinogenic (1; CRC); Carminative
(f; BGB); Cholagogue (2; APA; CAN; SHT); Cholekinetic (2; SHT); Choleretic (2; CRC;
KOM; HHB; PH2; SHT); Demulcent (f; CAN); Diuretic (1; APA; BGB; CAN); Emetic (1;
HHB); Gastrostimulant (2; APA; KOM; PH2); Hepatoprotective (1; APA; BGB);
Hepatotonic (2; CAN; EFS; PNC); Hypnotic (f; CRC; HHB); Laxative (1; APA; HHB);
Myorelaxant (1; APA; BGB; BRU); Narcotic (f; EFS); Nervine (f; BGB); Poison (f;
CRC); Secretagogue (1; BRU; KOM); Sedative (f; APA; CAN; EFS; HHB); Stimulant
(f; CRC); Stomachic (1; CAN; HHB); Tonic (f; CRC; EFS); Urinary Antiseptic (1;
CAN); Vermicide (1; BGB; EFS); Vermifuge (f; CRC; HHB).
INDICATIONS
Aging
(1; APA); Anorexia (2; PHR); Atherosclerosis (1; APA); Autoimmune Disease (1;
APA); Bilious Problem (2; APA; CAN; SHT); Cancer (1; APA); Cholecystosis (f;
BGB; CAN; HHB); Cholelithiasis (1; CAN; HHB); Cold (f; CRC); Constipation (1;
APA; HHB); Cough (f; CRC); Cramp (2; APA; BRU; KOM; PH2; SHT); Cystosis (1;
CAN; PNC); Dyspepsia (2; APA; BGB; BRU; KOM; PH2); Enterosis (2; APA; KOM);
Gallstone (1; CAN; HHB; PNC); Gas (f; BGB); Gastrosis (2; CRC; KOM); Gonorrhea
(1; CAN; GMH; HHB); Gout (f; APA; BGB; CRC); Head Cold (f; CRC); Heartburn (f;
BGB; BRU); Hepatosis (2; APA; CAN; CRC; HHB; PHR); Hypertonia (2; KOM);
Infection (1; CAN; CRC; EFS); Inflammation (1; APA); Insomnia (f; APA; CAN;
EFS; HHB); Jaundice (f; CRC; GMH); Lethargy (f; EFS); Nephrosis (f; BGB);
Nervousness (f; APA; CAN; EFS; HHB); Obesity (f; PNC); Otosis (f; CRC); Pain
(f; BGB; CRC); Prostatosis (f; BGB); Rheumatism (f; APA; BGB; CAN; EFS); Stomachache
(1; APA); Stone (1; BRU); Syphilis (f; CRC; HHB); Urogenitosis (f; GMH); VD (f;
CRC; HHB); Water Retention (1; APA; BGB; CAN); Worm (1; APA; BGB; CRC; EFS; HHB);
Wound (f; CRC).
INDICATIONS AND USAGE
Approved by
Commission E:
• Dyspeptic complaints
PRODUCT AVAILABILITY
Extract, tea, tincture
PLANT PART USED: Leaves
DOSAGES
DOSAGES
Do not exceed recommended dosage.
·
Adult PO: 0.2-3 g dried leaves
daily
·
Adult PO: 60-200 mg of dried
leaf tid or as a tea tid (Jellin et al, 2008)
·
Adult tincture: 1.5-6 ml/day
(1:5); 1.8-6 ml/day (1:10)(Mills, Bone, 2005)
·
Adult liquid extract: 0.7-2
ml/day (1:2) (Mills, Bone, 2005)
DOSAGES
Dosages
for oral administration (adults) for traditional uses recommended in older and
contemporary standard herbal reference texts are given below.
·
Dried Leaf 60–200 mg as an infusion three
times daily;(G7) 2–5 g as a tea.(G52)
·
Liquid Extract 0.1–0.3 mL (1 : 1 in 45%
alcohol) three times daily.(G7)
·
Tincture 0.5–2.0
mL (1 : 10 in 60% alcohol) three times daily.(G7)
DOSAGES
·
1–2 tsp (2-3 g) dry leaf/cup water (APA); 3 g dry leaf/day
(KOM); 4.5 g dry leaf/day (PHR; PH2); 1–2 g leaf (HHB);
·
60–200 mg as tea, 3 ×/day (CAN); 0.1–0.3 ml liquid extract (1:1
in 45% alcohol) 3 ×/day (CAN);
·
0.5–2 ml tincture (1:10 in 60% alcohol) 3 ×/day (CAN); 1–5 g
tincture or elixir (HHB); 5 drops boldo oil for urogenitary problems (GMH).
DOSAGES
MODE
OF ADMINISTRATION: Comminuted herb for infusions and other,
virtually ascaridol-free preparations for internal application. Because of the
ascaridol content, essential oil and distillates of Boldo leaf should not be
used.
DAILY DOSAGE: The average
daily dosage is 4.5 gm
PRECAUTIONS AND ADVERSE REACTIONS
No health hazards or side effects
are known in conjunction with the proper administration of designated
therapeutic dosages. The volatile oil should not be used, because it contains
up to 40% of the toxin ascaridole.
OVERDOSAGE
Signs of
paralysis are reported to appear following intake of very high dosages. A case
is described in the older scientific literature in which depression, color
hallucinations, sound hallucinations and partial motor aphasia occurred
following the consumption of boldine over a period of months.
CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS
CLASS 2B (JAD) 2D.
Contraindicated in gallstones, serious hepatosis, and obstruction of the bile
duct (AHP). “Hazards and/or side effects not known for proper therapeutic
dosages” (PH2). Still, PH2 cites an old source indicating that long-term
consumption of boldine led to color hallucinations, depression, partial motor
aphasia, and sound hallucinations (PH2). Commission E reports contraindications
for leaf: biliary obstruction, severe liver diseases. EO and distillates should
not be used because of their ascaridole content (AEH). CAN caution against
toxicity and irritation from the volatile oil. Because of the irritant oil, its
use in pregnancy and lactation is to be avoided (CAN). It’s nice to be cited by
Schulz, Hansel, and Tyler (1998), “Because the herb contains substances that
are potentially toxic (Duke, 1985), it is not recommended for long term use and
should not be taken during pregnancy” (SHT). But that could be carried as far
as the Delaney Clause, since all herbs (like all pharmaceuticals) contain
substances that are potentially toxic. Given internally in toxic doses, boldine
causes great excitement, exaggerates reflexes and respiratory movements,
increases diuresis, causes cramps and convulsions ending in death from centric
respiratory paralysis, the heart beating some time after respiration fails.
CONTRAINDICATIONS
Boldo is
contraindicated in patients with bile duct obstruction and those with severe liver
diseases. Patients who have gallstones should consult a physician before using
the drug.
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.
CONTRAINDICATIONS
Pregnancy category is 7;
Breastfeeding category is 5A.
Boldo should not be given to children. Persons with
neurologic or respiratory disease, renal disease, obstruction of the bile duct,
or severe hepatic disease should avoid the use of boldo. Persons with gallstones
should use this herb cautiously.
SIDE EFFECTS/ADVERSE REACTIONS
Very high doses
CNS: Paralysis,
exaggerated refl exes, convulsions, coma, death
RESP: Respiratory
depression
INTERACTIONS
Drug
Anticoagulants, antiplatelets: Boldo given with anticoagulants, antiplatelets can lead
to increased risk of bleeding (Jellin et al, 2008).
CNS depressants: Boldo
may increase the effect of these products.
EFFECTS
Boldo has been
shown to be antispasmodic, choleretic and to increase gastric secretions.
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)
CLIENT CONSIDERATIONS
ASSESS
·
Assess for central nervous
system reactions and respiratory depression. If either is present, discontinue
use of this herb.
ADMINISTER
·
Instruct the client to store
boldo in a cool, dry place, away from heat and moisture.
TEACH CLIENT/FAMILY
·
Inform the client that
pregnancy category is 7 and breastfeeding category is 5A.
·
Caution the client not to use
boldo in children. Keep boldo products out of the reach of children because
this herb is toxic in high doses.
·
Advise the client to avoid the
use of boldo if central nervous system disorder, respiratory disorder, or
severe hepatic disease is present.
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
Reduct- Te; 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 Ifuchol; Peptochol. Spain: Natusor Hepavesical; Nico Hepatocyn; Odisor;
Opobyl; Resolutivo Regium; Solucion Schoum. Switzerland: Boldocynara; Heparfelien;
Tisane hepatique et biliaire. UK: Adios; Boldex; Fenneherb Slim Aid; HealthAid Boldo-Plus;
Napiers Slimming Tablets; Reducing (Slimming) Tablets; Weight Loss Aid.
EXTRACTS
High
doses of the hydroalcoholic extract (= tincture) inhibit lipid peroxidation, (in
rat hepatocyte cultures) and protect such hepatocytes against various
xenobiotics (BRU). Although overdoses (injected) may cause cramping, boldine
has anticholinergic activity, causing relaxation of smooth muscle (from the rat
ileum) (BRU). EO LD50 = 130 orl rat; LD50 = 625–1250 mg/kg der rabbit (CAN).
Convulsant 70 mg/kg (CAN). The diuretic terpinen-4-ol is irritant (CAN). Alkaloids
probably underlie the choleretic activity. The total alkaloid content is more
choleretic than boldine alone (PNC). Ascaridole is toxic.
REFERENCE
Barnes, J., Anderson, L. A., and Phillipson, J. D. 2007. Herbal
Medicines Third Edition. Pharmaceutical Press. Auckland and
London.
Duke, J. A. with Mary Jo Bogenschutz-Godwin, Judi duCellier, Peggy-Ann K.
Duke. 2002. Handbook of Medicinal Herbs 2nd Ed. CRC Press
LLC. USA.
Gruenwald, J., Brendler,
T., Jaenicke, Ch. 2000. PDR for Herbal Medicines. Medical
Economics Company, Inc. at Montvale, NJ 07645-1742. USA
Linda S-Roth. 2010. Mosby’s Handbook Of Herbs & Natural
Supplements, Fourth Edition. Mosby Elsevier. USA
Figure 3. Primary Chemical Components and Possible Actions
(Linda, S-R. 2010)
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