Boldo
Scientific Name(s): Peumus boldus Molina
Common Name(s): Boldea, Boldoa, Boldu, Boldus
Medically reviewed by Drugs.com. Last updated on Mar 22, 2024.
Clinical Overview
Use
In vitro and animal studies suggest that boldo leaf extract and its constituent boldine have antioxidant, anti-inflammatory, and antimicrobial effects and have investigated potential applications in diabetes, GI disorders, cancer, sun protection, osteoporosis, renoprotection, and atopic dermatitis. However, clinical trial data are lacking to recommend use for any indication.
Dosing
No quality clinical trials exist to provide dosing recommendations for boldo leaf extract. Traditional doses include 1 to 2 teaspoons (2 to 3 g) of dry leaf per 240 mL of water; and 0.1 to 0.3 mL of liquid extract (1:1 in 45% alcohol) 3 times a day. Commercial preparations may contain ascaridole, a toxic constituent.
Contraindications
Contraindicated in liver disease and diseases of the bile duct, including gallstones.
Pregnancy/Lactation
Avoid use. Adverse effects have been noted in animal studies.
Interactions
Boldo ingestion may enhance the anticoagulant effect of warfarin; caution is warranted. Boldo may also decrease therapeutic tacrolimus levels; caution is warranted.
Adverse Reactions
Boldo-related adverse events described in case reports include anaphylaxis, prolonged QT interval, ventricular tachycardia, and hepatotoxicity.
Toxicology
No data.
Scientific Family
- Monimiaceae (Monimia)
Botany
Peumus boldus is an evergreen shrub or small tree native to central Chile, Argentina, Ecuador, Bolivia, and Peru. The plant grows up to 6 m in height. The woody, pleasant-smelling leaves, called boldo folium, are used medicinally.Pavela 2019 Small, green edible fruits are borne from small, pink-white flowers,Blumenthal 2000, Khan 2010, USDA 2014 which are also referred to as Boldu boldus (Molina) Lyons and Boldea fragrans Gay. Higher essential oil concentrations dwell in leaves from well-irrigated plants, and higher proportions of harvested leaves are found among trees grown under full light intensity.Vogel 2011
History
In Chile, the yellowish-green fruit is consumed, its bark is used in tanning, and the wood is used for charcoal. After noticing that local South Americans used the leaves medicinally, explorers introduced the herb to North America and Great Britain as a carminative for stomach, bladder, and liver complaints, and as a mild sedative. The name "boldu" has been attributed to the Mapuche words "weltum" (to sprout again) and "volitum" (to put out new roots). The plant is used as a laxative, choleretic (a stimulant of bile secretion), and diuretic, as well as in the treatment of digestive disorders and hepatic diseases. The leaves have also been used for worms, urogenital inflammations (eg, gonorrhea, syphilis), gout, rheumatism, head colds, and earaches. Boldo extract has traditionally been used in folk medicine, and also as a flavoring for alcoholic beverages.Blumenthal 2000, Carbajal 2014, Duke 2002, Khan 2010 A patent has been granted for the use of boldo in cosmetic and dermatological products.Pauley 2000
Chemistry
Boldo leaves contain aporphine alkaloids (0.25% to 0.5% [of which about 12% to 19% is boldine]), volatile oil (2.5%), flavonol glycosides, resin, and tannins. At least 17 benzylisoquinoline alkaloids are present in the leaves, including laurolitsine, reticuline, boldine, and isoboldine. Flavonoids include catechin, peumoside, boldoside, fragroside, and gallic and tannic acids. Boldine is also present in the bark of the tree. Up to 67 compounds have been identified in P. boldus, with ascaridole, p-cymene, terpineol, and 1,8-cineole (eucalyptol) as the main components.de Souza 2019, Gómez 2018, Pavela 2019
Genetic variation in the essential oil and alkaloid content has been investigated. Variability depends on season, location, sex of the plant, canopy height, leaf age, and light intensity. Various methods have been described for the analysis of boldo leaves and preparations.Cámara 2010, Duke 2002, Hroch 2013, Khan 2010, O'Brien 2006, Petigny 2013, Simirgiotis 2010, Vogel 1996, Vogel 1999
Uses and Pharmacology
Anti-inflammatory effects
Animal data
The dried hydroalcoholic extract of the boldo plant reduced the inflammatory process in a rat model of carrageenan-induced edema.Lanhers 1991 In vitro, boldine has also been shown to inhibit prostaglandin synthesis in rat aortal rings.Backhouse 1994, Khan 2010
Antimicrobial effects
Animal and in vitro data
P. boldus aqueous extract displayed potent activity against Helicobacter pylori via inhibition of urease activity and adhesion to human adenocarcinoma gastric cells in vitro.Pastene 2014
Antifungal, herbicidal, and antihelminthic effects have been shown in vitroBluma 2008, Passone 2014, Verdeguer 2011, Vila 1999 and in animal studies.van Krimpen 2010 Efficacy may be due to ascaridole content.Blumenthal 2000, Khan 2010 Mouse peritoneal macrophages infected with Leishmania amazonensis for 24 hours and exposed to 50 mcg/mL of boldine for 24 hours showed a 50% reduction of infected macrophages.Salama 2017 When the concentration was doubled, the reduction of infected macrophages rose to 81%. When analyzing cell parasite burden, boldine treatment was associated with a reduction in the number of parasites per macrophage.
Antioxidant activity
Boldo tea has traditionally been used for the antioxidant properties of its components.
Animal, in vitro, and experimental data
Antioxidant activity of boldine and boldo leaf extracts has been demonstrated in multiple animal and in vitro studies.O'Brien 2006, Speisky 1994 Boldo tea treated with immobilized tannase entrapped in calcium alginate beads resulted in removal of natural tannins and a 5-fold increase in antioxidant activity of boldo tea.de Lima 2018 Applications of the observed antioxidant effects include improved endothelial function, especially in diabetic rats,Hernández-Salinas 2013, Lau 2013, Lau 2013 and protection against induced hepatic damage,Cordero-Pérez 2013, Fernández 2009 which may also be the mechanism of action in other observed effects. When brine shrimp were exposed to solutions of the essential oils of boldo and boldo tea, the tea preparation showed better antioxidant activity.de Souza 2019
Antipyretic effects
Animal data
An antipyretic effect of boldo has been shown in rabbits.Khan 2010
Atopic dermatitis
Animal and in vitro data
A 0.2% concentration of boldo extract used to treat keratinocytes collected from atopic and healthy canines positively affected production and secretion of antimicrobial peptides without stimulating an inflammatory reaction.Santoro 2017 Furthermore, tumor necrosis factor alpha levels increased and interleukin-8 level decreased only after exposure to a more potent extract of boldo 2%. Based on these in vitro results,Santoro 2017 a 0.1% concentration of P. boldus in combination with Spiraea ulmaria plant extract was tested on dogs with atopic dermatitis.Santoro 2018 Ten pumps of the 0.1% solution were applied to the affected area(s) every 24 hours for 4 weeks. Reductions in overall bacterial loads, specifically of Staphylococcus spp., were observed, suggesting that this combination has a positive effect on bacterial burden in atopic dogs.Santoro 2018
Cancer
Animal and in vitro data
Both boldine alone and boldo leaf extracts have shown antiproliferative effects in vitro.Falé 2012, Gerhardt 2009, Gerhardt 2014, O'Brien 2006 Protective effects against ultraviolet-mediated DNA damage have been demonstrated in melanoma cells.Hidalgo 1998, O'Brien 2006, Russo 2011 When the anticancer drug cisplatin was coadministered with 10 mg/kg of nano-encapsulated boldine (NBol) once daily for 30 days in mice with induced hepatocarcinoma, toxic adverse effects of cisplatin therapy were reduced; the combination was associated with reductions in liver damage and architectural damage to the kidneys, and also with regeneration of tissue without reducing cisplatin's anticancer efficacy. Cisplatin plus NBol also lowered AST, ALT, and reactive oxygen species levels.Mondal 2018
Diabetes/Metabolic syndrome
Animal and in vitro data
In vitro results indicate boldine modulates adiponectin levels and regulators of adipogenesis, suggesting potential beneficial effects on obesity-related diseases.Yu 2009 In diabetic rats given boldine for 7 days, slight decreases in plasma glucose levels were observed, but with no effect on the plasma lipid profile. A decrease in body weight was also observed.Lau 2013 In rats administered boldine over 10 weeks, a protective effect against increases in glucose and blood pressure was demonstrated; markers of renal damage also improved.Hernández-Salinas 2013 Antihypertensive effects have been shown in spontaneously hypertensive rats.Lau 2012 Boldine 20 mg/kg via intraperitoneal injection for 7 days decreased systolic blood pressure in hypertensive rats and reversed endothelial dysfunction in aortas of diabetic (type 1 and type 2) rats. The same dose also slightly decreased glucose levels in type 1 diabetic rats.Lau 2015
GI disorders
Animal data
The flavones boldoside and peumoside suppressed an induced excitation in mice and demonstrated a marked spasmolytic effect in rabbits experiencing gut spasm.Borkowski 1965 Boldine demonstrated anti-inflammatory properties in experimental colitis models.Gotteland 1997, Salati 1984 Mice with docusate sodium (dioctyl sodium sulphosuccinate)–induced ulcerative colitis treated with boldine 50 mg/kg orally for 7 days had less weight loss and better disease activity index scores (calculated based on daily monitoring of body weight loss, stool consistency, and blood in the stool) compared with untreated mice. Boldine also decreased spleen weights, suppressed shrinkage of colon length, blocked inflammatory cell infiltration, and restored architecture of the colon epithelium.Pandurangan 2016
Clinical data
In an older study, dry boldo extract prolonged orocecal transit time in 12 healthy volunteers.Gotteland 1995
Insecticidal/Larvicidal activity
In vitro and experimental data
In vitro and experimental studies suggest that essential oils extracted from the leaves of P. boldus may have potential applications in larvicides and insecticides, provided the level of ascaridole, which is harmful to vertebrates, is low.de Castro 2016, Pavela 2019
Osteoporosis
Animal data
A dosage of boldine 20 mg/kg/day for 6 weeks improved ovariectomy-induced bone loss in mice, based on elevations in bone mineral density and bone volume/total volume. In addition, boldine partially inhibited bone resorption, without affecting bone formation, in vivo and in vitro.Chen 2018
Radiolabeling effects
In vitro data
Boldo has been studied for its effects on radioactive labeling of red blood cells and plasma proteins, tracing uptake by cells.Braga 2000, Reiniger 1999
Renoprotection
Animal data
In a study evaluating effects of boldine on the progression of kidney disease in 2K1C hypertensive rats, boldine 50 mg/kg/day by gavage for 6 weeks reduced the proteinuria/creatininuria ratio, and slightly reduced systolic blood pressure compared to control. Boldine also prevented an increase in angiotensin converting enzyme-1 and reduced oxidative stress, fibrosis, and inflammation, suggesting a role in reducing kidney damage.Gómez 2018
Skeletal muscle effects
In vitro data
In a study in a mouse phrenic nerve-diaphragm, boldine demonstrated neuromuscular blockadeKang 1998; in another study evaluating effects of boldine on skeletal muscle using mouse diaphragm and isolated sarcoplasmic reticulum membrane vesicles, boldine sensitized the ryanodine receptor and induced calcium release from storage sites in isolated skeletal muscle.Kang 1998
Sun protection
Clinical data
One study using boldine as a sunscreen preparation reported a sun protection factor ranging from 2.3 to 4.4, comparable to that of Nivea Sun Spray, which had a range of 3.6 to 5.Rabinovich 2018
Dosing
No quality clinical trials exist to provide dosing recommendations for boldo leaf extract. Traditional doses include 1 to 2 teaspoons (2 to 3 g) of dry leaf per 240 mL of water; and 0.1 to 0.3 mL of liquid extract (1:1 in 45% alcohol) 3 times a day.Duke 2002 Commercial preparations may contain ascaridole, a toxic constituent.Blumenthal 2000
Pregnancy / Lactation
Avoid use. Adverse effects have been noted in animal studies.
A hydroalcoholic extract of boldo and boldine demonstrated abortive and teratogenic actions in rats.Almeida 2000 Another report found no malformations in the fetus following short-term administration, but abortifacient and teratogenic effects were noted at high doses.O'Brien 2006 Some labels on boldo products have highlighted the presence of sparteine, an abortive agent.de Souza 2019
Interactions
Inhibition of platelet aggregation has been shown in one in vitro study.O'Brien 2006 A case report describes a potential interaction with warfarin, which returned upon rechallenge with the combination herbal preparation boldo-fenugreek; both components have demonstrated antiplatelet activities.Lambert 2001 Theoretically, increased anticoagulant effects can be expected when warfarin is combined with coumarin-containing herbal medicines (eg, boldo).Izzo 2005 Because boldo has purported diuretic effects, increased effects of cardiac glycosides due to potassium depletion are theoretically possible.Vogel 2005 Another case report outlines a potential interaction with tacrolimus. A renal transplant patient presented to the clinic, where his labs displayed subtherapeutic levels of tacrolimus. Upon questioning, the only change in his medication regimen was the addition of boldo 300 mg capsules, which he had been taking twice daily for several weeks. Upon discontinuation of the supplement, tacrolimus levels normalized.Carbajal 2014
Adverse Reactions
Boldo-related adverse events described in case reports include anaphylaxis in an atopic individual.Monzón 2004 In one case report, a woman taking a combination preparation containing dandelion, focus, and boldo for obesity experienced a prolonged QT interval and ventricular tachycardia.Agarwal 2006 A case of hepatotoxicity (increased liver enzymes) was noted following use of boldo leaf extract as a component of a laxative preparation.Piscaglia 2005 The German Commission E cautions against the use of boldo leaf in severe liver disease and disease of the bile duct, including gallstones, and only approves the use of boldo preparations devoid of ascaridole.Blumenthal 2000
Data collected between 2004 and 2013 from 8 US centers in the Drug-induced Liver Injury Network revealed that 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (709) of cases were related to prescription medications. Of the 130 cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanics/Latinos compared with non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the proportion of severe liver injury cases was significantly higher for supplements than for conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, 175 had identifiable ingredients, of which boldo was among the 32 (18%) single-ingredient products.Navarro 2014
One case report describes a 12-year-old girl who presented to the hospital with complaints of panic attacks accompanied by hallucinations after consumption of boldo leaf infusions. It was determined that she had consumed 1.16 mg of boldine nightly for 3 days.Chaboussant 2014 Avoiding use in children is advisable.
Toxicology
High doses of boldine can cause severe adverse effects, toxicity, or death. The median lethal dose in mice was 250 mg/kg. Death in animals resulted from sequelae, leading to respiratory failure.O'Brien 2006 Death in rats also resulted from neurotoxic effects, including depletion of dopaminergic neurons.Mejía-Dolores 2014 Long-term administration resulted in increased liver enzymes in rats, but not histological evidence of hepatotoxicity.O'Brien 2006 Mutagenicity tests have demonstrated equivocal results.Khan 2010, Moreno 1991, O'Brien 2006, Tavares 1994
Index Terms
- Boldea fragrans Gay
- Boldu boldus (Molina) Lyons
References
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