Lapachol has interesting antimicrobial effects and anticancer effects that should be further investigated; however, high doses in humans can cause nausea, vomiting, and an anticoagulant effect.
[LFODPKM ] Letter Key
Latin Name
Tabebuia impetiginosa (Mart.) ex DC (Standl.), T. heptaphylla (Vell.) Toledo
Family
Bignoniaceae
Other Common Names
Lapacho, taheebo, ipes, ipe roxo, and trumpet bush
Description
Tabebuia is a genus of about 100 hardwood trees (mostly evergreen) native to Central and South America and the West Indies.
Part Used
Inner bark
Known Active Constituents
The heartwood contains 2% to 7% lapachol, a naphthoquinone derivative, and other naphthoquinone derivatives (1). A petroleum extract of T. impetiginosa heartwood was found to contain 3.6% lapachol and lesser amounts of 
-lapachone, 
-lapachone, and dehydro--lapachone. Lapachol is not a major constituent of Tabebuia barks, and a Canadian survey of 12 commercial taheebo products found that only two contained lapachol (in very low amounts, 0.003% to 0.004%) (1). Two cyclopentene dialdehydes with antiinflammatory activity were recently identified in pau d’arco (2).
Mechanism/Pharmacokinetics
Lapachol appears to be a vitamin K antagonist, and thus may affect the vitamin K-dependent ligand activation of the Ax1 receptor tyrosine kinase (3). -lapachone activates the DNA-unwinding activity of topoisomerase I (4).
[Outline]
[CAO ] Letter Key
Clinical Trials
- Cancer
- A phase I toxicology study of lapachol in 19 patients with advanced nonleukemic tumors and two patients with chronic myelocytic leukemia in relapse was sponsored by the National Cancer Institute. Subjects received oral doses of lapachol (250 to 3,750 mg/day) (5). Although this study was a toxicity study, not an efficacy study, one patient with metastatic breast cancer had a regression in one of several bone lesions (other patients did not have objective responses to the drug). Lapachol in doses of 1,500 mg/day or higher caused nausea, vomiting, and prolonged prothrombin time. No hepatic or renal toxicity or myelo-suppression was seen. The Investigational New Drug application (IND) for lapachol was closed in 1970. A later experiment noted that the anticoagulant effects of lapachol could be reversed by the administration of vitamin K. (It is not clear, however, whether or not this would reverse any beneficial effect.)
- An uncontrolled study of nine patients (all previously treated conventionally) found that lapachol (20 to 30 mg/kg/day p.o. × 20 to 60 days or longer) resulted in subjective improvements, including pain reduction, in all patients. Two partial tumor regressions (apparently in a patient with basal cell carcinoma of the cheek metastasized to the cervix and a patient with ulcerated squamous cell carcinoma) and one complete tumor regression (apparently in a patient with hepatic adenocarcinoma) were noted. It is not stated how regressions were measured or how long they lasted.
Animal/In Vitro
- Cancer
- In animal models, lapachol has cytotoxic effects. It has been found to have antitumor activity in Walker 256 and sarcoma Yoshida ascites cells but did not have significant activity in sarcoma 180, L 1210 leukemia, and adenocarcinoma (5). A crude extract of pau d’arco stimulated macrophages, killed Lewis lung carcinoma cells in culture, and reduced lung metastases in mice after surgery (5). Lapachol had growth inhibitory effects on four melanoma cell lines and a renal cell carcinoma line (6).
- -lapachone enhances the lethality of x-rays against human laryngeal epidermoid carcinoma cells and enhances the cytotoxic effects of x-rays and other agents that induce DNA strand incisions; it does not appear to create lethal DNA lesions (4).
- Snakebite
- T. rosea (a different species than pau d’arco) and several other traditional remedies for snakebite administered orally or intramuscularly significantly reduced the lethal effect of Bothrops atrox venom (7).
- Psoriasis
- -lapachone reduced the growth of human keratinocytes (IC50 value of 0.7 mM) to an extent similar to the antipsoriatic drug anthralin, indicating that it may have potential as an antipsoriatic agent.
- Antimicrobial
- Although pau d’arco is reputed to have antimalarial effects, in an in vitro experiment, lapachol exhibited only low inhibition of schizogony (reproduction of the malarial parasite) (8). Lapachol and other naphthoquinones reduced skin penetration by Schisoma mansoni cercariae (9).
- Ulcers
- Lapachol derived from teak (Tectona grandis) (5 mg/kg p.o. b.i.d.) inhibited gastric and duodenal ulcers in rats and guinea pigs (10).
- Analgesia
- Lapachol and an extract from T. chrysotricha had analgesic effects in mice (11).
Other Claimed Benefits/Actions
- Cancer
- Rheumatism
- Antibiotic
- Cystitis
- Gastritis
- Prostatitis
- Ulcers
- Liver problems
- Asthma
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[ADPT ] Letter Key
Adverse Reactions
Lapachol in doses of 1,500 mg/day or higher caused nausea, vomiting, and prolonged prothrombin time (5).
Drug Interactions
None reported
Pregnancy/Lactation
No information available.
Animal Toxicity
- Injected i.p. into rats, the LD50 of lapachol was 1,600 mg/kg, -lapachone 80 mg/kg, and xyloidine 600 mg/kg. Ten doses of lapachol 500 mg/kg caused death, as did six doses of -lapachone at 9 mg/kg (12).
- Pregnant Wistar rats were treated with control (water), vehicle (0.5 mL hydroalcoholic solution), or lapachol (20 mg in 0.5 mL hydroalcoholic solution) by oral gavage from the eighth to the twelfth day of pregnancy. There was no effect on maternal body weight or food intake but there was 100% fetal/embryo mortality (13).
[Outline]
Q: What are lapacho colorado and lapacho morada?
A: Teas sold as lapacho colorado are made from Tabebuia impetiginosa (also called T. avellanedae in Brazil). Teas sold as lapacho morada are said to be from a high-altitude species called Tabebuia altissima, an imaginary species (Tabebuia does not grow at high altitude). Some teas sold as lapacho morada or lapacho colorado do not contain Tabebuia at all, but contain Tecoma curialis, which is closely related (14).