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Taheebo

Scientific Name(s): Tabebuia avellanedae Lorentz ex Griseb.
Common Name(s): Ipé Roxo, Lapacho colorado, Lapacho morado, Pau d'Arco, Red lapacho, Taheebo

Medically reviewed by Drugs.com. Last updated on Dec 1, 2021.

Clinical Overview

Use

Taheebo has traditionally been used to treat a wide range of conditions, including bacterial infections, blood coagulation, cancer, and inflammatory diseases. Various fractions from T. avellanedae have shown astringent, anti-inflammatory, antibacterial, antifungal, diuretic, anticoagulant, laxative, and anticancer properties, among others. However, clinical trial data are lacking to recommend use for any indication.

Dosing

Clinical information is lacking to provide dosing recommendations for taheebo.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Taheebo is generally considered safe, with reported adverse events generally being mild.

Toxicology

No data.

Scientific Family

  • Bignoniaceae (trumpet creeper)

Botany

Tabebuia spp., such as the pau d'arco tree, belong to the Bignoniaceae plant family. T. avellanedae is an evergreen canopy tree native to the Amazon rainforest and adjacent areas (equatorial and tropical forests) of Central and South America, where it is popularly referred to as ipê roxo. Taheebo is obtained from the bark and hardwood of the tree.(Balassiano 2005, Byeon 2008, Gómez Castellanos 2009) T. avellanedae is synonymous with Tabebuia impetiginosa (Mart. ex DC.) Standl, Tabebuia serratifolia (Vahl) Nichols, Handroanthus impetiginosus (Mart, ex DC.) Mattos, Tabebuia heptaphylla Vell. Toledo, and Tabebuia ipé Mart. ex Schum. The distinct but related species Tecoma curialis Solhanha da Gama is sometimes marketed under the same names.

History

The inner bark and hardwood of T. avellanedae have been used medicinally by native South American populations for centuries.(Balassiano 2005) Taheebo is obtained from the purple-colored bark of the tree and has been used in folk medicine to treat bacterial infections, blood coagulation, cancer, and inflammatory diseases.(Balassiano 2005, Byeon 2008) Its use may predate the Incas. For more than 1,000 years, taheebo was one of the primary medicines used by the Callawaya tribe. Taheebo has been used as a poultice and concentrated tea to treat a variety of skin conditions, including fungal infections and skin cancers.(Byeon 2008) A decoction prepared from the inner bark has been used internally to treat bacterial and fungal infections, fever, syphilis, malaria, trypanosomiasis, and stomach and bladder disorders.(Gómez Castellanos 2009) In 1967, a Brazilian news magazine reported "miraculous" cures in cancer patients using red lapacho. Between 1960 and 1990, the US National Cancer Institute (NCI) conducted research on the use of natural products, including lapachol and beta-lapachone (active components of taheebo), for the treatment of cancer.(Gómez Castellanos 2009) Studies using lapachol were discontinued due to toxicity (not specified),(Lu 2013) but research evaluating the anticancer activity of beta-lapachone has continued.(Hartner 2007, Khong 2007, Shapiro 2005) In 1999, the US Food and Drug Administration (FDA) listed red lapacho tea as a dietary supplement and an "herb used to alleviate conditions and symptoms of cancer."(Gómez Castellanos 2009)

Chemistry

The major active compounds in the hot water extract of T. avellanedae inner bark are naphthoquinones, furanonaphthoquinones, anthraquinones, benzoic acid derivatives, benzaldehyde derivatives, iridoids, coumarins, and flavonoids.Byeon 2008

The 2 main bioactive components of Tabebuia spp. bark responsible for its pharmacologic activity are lapachol and beta-lapachone. The chemical name for lapachol is 2-hydroxy-3-(3-methyl-2 buthenyl)-1,4-naphthoquinone. The chemical name for beta-lapachone, an isomer of lapachol, is 3,4-dihydro-2,2-dimethyl-2H-naphtol[1,2-b]pyran-5,6-dione.Gómez Castellanos 2009

Uses and Pharmacology

Commercially available botanical drug material is of varying quality and composition,(Gómez Castellanos 2009) making assessments of product clinical efficacy challenging; the bioscientific evidence for products derived from T. impetiginosa is insufficient. When pharmacologic actions of the whole plant extract were compared with those of its isolated constituents, potency appeared to decline with purification.(Gómez Castellanos 2009)

Various fractions from T. avellanedae have shown astringent, anti-inflammatory, antibacterial, antifungal, diuretic, anticoagulant, laxative, and anticancer properties, among others.(Byeon 2008) However, no clinical studies of preparations derived from taheebo have been conducted.

Anti-inflammatory activity

Animal and in vitro data

In an in vitro study, 5 novel compounds isolated from the water extract of T. avellanedae showed anti-inflammatory properties.(Suo 2012) The water extract of T. avellanedae blocks inflammatory mediators in vitro and in vivo; it suppresses the production of prostaglandin E2 and nitric oxide and blocks the mRNA expression of their catalyzing enzymes.(Byeon 2008, Zhang 2016) In an in vivo study in mice, a 200 mg/kg dose of taheebo ethanolic extract showed anti-inflammatory effects.(Lee 2012) In a mouse macrophage line, taheebo polyphenols reversed free fatty acid–induced increases in inflammatory markers in a dose-dependent manner, without affecting overall cell viability. The mechanism involved reversal of upregulation of cyclooxygenase 2 (COX-2) mRNA more than of COX-1.(Ma 2017)

Antimicrobial activity

In vitro data

In studies evaluating the antimicrobial activity of T. impetiginosa, methanol extracts of the inner bark showed weak to moderate activity against Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus casei, and Escherichia coli, and strong activity against Clostridium paraputrificum, Clostridium perfringes, and Helicobacter pylori. The 2 compounds thought to be responsible for the antibacterial activity were lapachol and anthraquinone-2-carboxyl acid. In a study evaluating the activity of taheebo against H. pylori, lapachol was more effective than metronidazole, but far less effective than amoxicillin and tetracycline.(Gómez Castellanos 2009, Park 2005, Park 2006) When tested in vitro against methicillin-resistant Staphylococcus aureus, beta-lapachone demonstrated synergistic activity with conventional agents (eg, beta-lactams, fluoroquinolones, carbapenems).(Macedo 2013) Lapachol has demonstrated activity against mycobacteria. In cell culture, lapachol was more effective intracellularly than extracellularly and demonstrated immunomodulatory effects (inhibition of the surface expression of the costimulatory molecule cluster of differentiation 86 [CD86]), which may enhance the capability of the host cell to control mycobacterial invasion.(Oliveira 2010)

Antiparasitic activity

Animal and in vitro data

In an in vitro study, lapachol and antimony, bismuth, and tin complexes of lapachol demonstrated antiparasitic activity.(Barbosa 2014, Rocha 2013) In various experiments, Tabebuia extracts inhibited interleukin 2 (IL-2)–dependent T-lymphocyte activation and proliferation, but had no effect on cytokine expression (IL-2 and tumor necrosis factor alpha). Immune inhibitory effects of Tabebuia were not mediated by beta-lapachone and were observed in aqueous but not ethanol extracts.(Böhler 2008) When antileishmanial activity of lapachol, isolapachol, and dihydrolapachol, as well as various soluble derivatives, was tested in vitro and in vivo, all lapachol compounds demonstrated activity against Leishmania in vitro; in vivo, a difference between treated and untreated mice was observed with only 1 of the 5 tested compounds 5 weeks after parasite injection. No toxicity was evident at concentrations similar to the 50% inhibitory concentration.(Lima 2004) Lapachol, beta-lapachone, and their derivatives demonstrated anthelmintic activity against Toxocara canis larvae both in vitro and in vivo in mice.(Mata-Santos 2015)

Antipsoriatic activity

In vitro data

In vitro, beta-lapachone has been shown to have antipsoriatic activity.(Gómez Castellanos 2009)

Cancer

In vitro data

In a series of studies, T. impetiginosa showed activity against a wide range of cancer cell lines, including Walker 256 carcinoma, prostate cancer, human promyelocytic leukemia, breast cancer, ovarian cancer, epidermoid laryngeal cancer, esophageal cancer, radioresistant human malignant melanoma, lung adenocarcinoma, cervical cancer, and osteosarcoma cells.(Bang 2016, Gómez Castellanos 2009, Inagaki 2013, Inagaki 2015, Kandioller 2013, Mukherjee 2009, Rao 1968, Sunassee 2013)

Beta-lapachone is considered the main antitumor compound, demonstrating activity against several tumor cell lines, including leukemia, lung, prostate, and breast cancers, as well as several multidrug-resistant cell lines.(Gómez Castellanos 2009, Kung 2014)

Lapachol is purported to have anticancer properties. While the mechanism of action is unknown, lapachol is involved in the inhibition of oxidative phosphorylation, activation of CYP-450 reductase, and enhancement of peroxidation of lipids in sarcoma cells.(Balassiano 2005, Fiorito 2014) Studies in cell cultures show that lapachol causes alterations in the protein profile and inhibits cellular invasiveness in HeLa cells (a human cancer cell line), suggesting antimetastatic activity.(Balassiano 2005)

Another potential anticancer mechanism proposed is the inhibition of topoisomerase I. Investigations show that lapachol induces oxidative stress via generation of reactive oxygen species, which leads to apoptosis and cell cycle arrest.(Kandioller 2013) In other research, beta-lapachone initiated apoptosis only in transformed cells without causing DNA damage.(Gómez Castellanos 2009) Furthermore, beta-lapachone increased activation of pro-apoptotic factor JNK and decreased activation of the cell survival/proliferation factors PI3K, AKT, and ERK.(Kung 2014) Beta-lapachone reportedly induces apoptosis by modulating E2F-1 expression, which activates the G1/S-phase checkpoint.(Shapiro 2005) An aqueous extract of pau d'arco stimulated the MAPK/ERK 1/2 pathway, leading to stimulation of nuclear factor erythroid 2–related factor 2 (Nrf2)–dependent gene expression.(Richter 2014) In vitro research using an aqueous extract of taheebo in estrogen receptor–positive breast cancer cells demonstrated upregulation of apoptosis-specific and xenobiotic metabolism–specific genes and downregulation of cell cycle regulatory and estrogen-responsive genes.(Mukherjee 2009) In the presence of probiotics, lapachol can be converted to a more active cytotoxic compound against breast cancer cell lines than lapachol alone.(Oliveira Silva 2014)

It is generally understood that nicotinamide adenine dinucleotide (NAD)(P)H:quinone oxidoreductase (NQ01) activity is an important determinant of beta-lapachone cytotoxicity and that NQ01 is overexpressed in most common types of cancer. NQ01 catalyzes the redox cycling of beta-lapachone via production of an unstable hydroquinone. Under aerobic conditions, this unstable quinone is quickly oxidized back to the parent quinine, resulting in futile cycling between the 2 forms of beta-lapachone and a rapid increase in intracellular calcium, mitochondrial membrane depolarization, loss of adenosine triphosphate, DNA fragmentation, and, finally, apoptosis. Beta-lapachone acts, in part, through upregulation of NQ01.(Lamberti 2013) In leukemia cells, beta-lapachone is directly cytotoxic. It decreases cell viability and telomerase activity resulting from downregulation of telomerase reverse transcriptase.(Moon 2010)

Clinical data

The NCI studied the anticancer effects of the lapachol component of taheebo in the 1960s. Phase 1 clinical trials evaluating oral lapachol dosages of up to 4,000 mg/day showed no therapeutic effect, and it was determined that inadequate serum concentrations were achieved with oral administration. The Investigational New Drug Application for lapachol was closed in 1970.(Gómez Castellanos 2009, Kung 2014)

A series of phase 1 and 2 clinical trials have been conducted with beta-lapachone (ARQ 501) in patients with cancer. Early signs of clinical activity were demonstrated.(Hartner 2007, Khong 2007, Shapiro 2005)

Colitis

Animal data

In a murine model, oral administration of T. avellanedae water extract was protective against induced colitis. Mice treated with the extract exhibited much less diarrhea and less fecal blood. The mechanism involved induction of the differentiation of anti-inflammatory T-helper cells (ie, Th2, Treg), decreases in proinflammatory cytokines (ie, IL-12, IL-6, tumor necrosis factor alpha), and increases in the anti-inflammatory cytokine IL-10 in intestinal dendritic cells and macrophages from mesenteric lymph nodes.(Park 2017)

Dermatitis

Animal data

In an atopic dermatitis mouse model, oral administration of an ethanol extract of T. avellanedae ameliorated dermatitis-like symptoms, decreased dermatitis scores, and prevented the epidermal thickening observed in untreated controls in a dose-dependent manner. These effects at 120 mg/kg and 240 mg/kg doses were comparable to the effects of prednisolone. Mechanisms involved reductions in histamine, immunoglobulin E, IL-4, IL-5, and proinflammatory cytokines (ie, interferon-gamma), with the 240 mg/kg dose being comparable to prednisolone.(Park 2018)

Endurance capacity

Animal data

A single dose of taheebo water extract increased endurance capacity (eg, running time) as well as plasma glucose and glycogen levels in the skeletal muscles of mice. In contrast, glycerol in skeletal muscle and the liver decreased, as did blood urea nitrogen.(Yada 2018)

Hypotensive effects

Animal data

Evidence in rats suggests that a seminatural naphthoquinone derivative of lapachol, 3-hydroxy-4-(hydroxyimino)-2-(3-methybut-2-enylnaphtalen-2[4H])-one can induce hypotension.(Dantas 2014)

Obesity

Animal data

In mice fed a high-fat diet, administration of an ethanolic extract of taheebo (150 mg/kg of body weight daily by gavage) interfered with obesity and fat accumulation by regulating gene expression related to lipid metabolism.(Choi 2014) In ovariectomized mice with high-fat diet–induced obesity (menopause-induced obesity model), oral administration of an n-butanol taheebo extract led to reductions in body weight, peritubal fat, perirenal fat, and mesenteric fat compared with controls, with no difference in food intake. No differences were found in organ weights, lipid parameters, adiponectin, resistin, or serum glucose between the 2 groups.(Iwamoto 2016)

Osteoarthritis

Animal data

In a rat model of osteoarthritis, oral administration of an ethanol extract of T. avellanedae increased the pain threshold in a manner comparable to positive controls without side effects. The effect was observed at low doses and was not dose dependent. Severe degradation of articular cartilage observed in untreated controls was inhibited with taheebo extract, which also exhibited a dose-dependent chondroprotective effect that was better than the positive control methylsulfonylmethane. X-ray results confirmed the histopathological outcomes.(Park 2017)

Vascular effects

In vitro data

Taheebo is capable of inhibiting platelet aggregation and vascular smooth muscle proliferation. While the mechanism of action is unclear, the antiplatelet effects may be due to suppression of arachidonic acid and collagen liberation, and the inhibition of vascular smooth muscle proliferation may be due to suppression of phosphorylated mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) activation.(Son 2006)

Wound healing

Animal and in vitro data

In a study in mice, scrape or burn wounds treated with beta-lapachone ointment healed faster than those treated with a control ointment. In cell cultures, beta-lapachone induced macrophage proliferation and increased vascular endothelial growth factor release from macrophages.(Fu 2011, Kung 2008)

Dosing

Clinical information is lacking to provide dosing recommendations.

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Taheebo is generally considered safe.(Gómez Castellanos 2009)

The isolated compound lapachol is associated with interference with the biological cycle of vitamin K. When consumed as red lapacho tea, which contains all components of taheebo including some pro–vitamin K compounds, the effect appears to be canceled.(Gómez Castellanos 2009)

Exposure to wood and/or wood dust from Tabebuia spp. can lead to asthma(Algranti 2005) and fixed eruption (erythematous, pruritic, hyperpigmented skin eruptions).(Landry 2018)

Pau d'arco tea can reportedly cause nausea and vomiting.(Cheng 2012)

Hemolytic anemia has been reported as a limiting toxicity in animals.(Lima 2004)

When administered to patients with cancer, beta-lapachone did not exhibit dose-limiting toxicity. Adverse events were mild and included anemia, hemolysis, hyperbilirubinemia, edema, nausea, constipation, and fatigue.(Hartner 2007, Khong 2007, Shapiro 2005)

Toxicology

No toxicity has been reported in humans for the bark extract or its main constituents.

Index Terms

  • Handroanthus impetiginosus (Mart, ex DC.) Mattos
  • Tabebuia heptaphylla Vell. Toledo
  • Tabebuia impetiginosa (Mart. ex DC.) Standl
  • Tabebuia ipé Mart. ex Schum
  • Tabebuia serratifolia (Vahl) Nichols
  • Tecoma curialis Solhanha da Gama

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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Further information

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