Chaparral (Larrea tridentata): A Comprehensive Reference
1. Identity and Botanical Description
Scientific and Common Names
Chaparral is prepared from the leaves of the evergreen desert shrub known as creosote bush (Larrea divaricata, subspecies tridentata), which is found in the southwestern United States and Mexico. The plant is placed within the family Zygophyllaceae, a small but showy family, also called the Caltrops family, and this makes it related to Guaiacum and Tribulus terrestris (Puncturevine).
Creosote bush, Larrea tridentata, is known as chaparral or greasewood in the United States and as gobernadora or hediondilla in Mexico. The common Spanish name hediondilla means "little smelly one," because the bush has a strong odor similar to the smell of creosote (a distillate of coal/wood tar used as a wood preservative), and gobernadora means "governess," because the bushes can dominate an area by creating an adverse environment for the growth of other plants, resulting in a monoculture in some areas.
The name chaparral (Larrea tridentata, creosote bush) is also sometimes used for other desert plants such as Larrea mexicana, Larrea glutinosa, Larrea nitida, and Larrea caneifolia, which are all widely used, for instance to cure colds, diarrhea, urinary tract infections, rheumatism, and skin problems, or to reduce body weight.
Geographic Distribution and Habitat
The creosote bush (Larrea tridentata) grows across the deserts of the southwestern United States and northern Mexico. Larrea tridentata, also known as Larrea divaricata, Larrea, chaparral, or creosote bush, is a shrubby plant which dominates some areas of the desert southwest in the United States and Northern Mexico as well as some desert areas of Argentina.
One remarkable feature of the chaparral bush is the complex resinous coating on the leaves that serves as a chemical defense against grazing by herbivores and against attack by insects. The chemicals in the resin find their way into the desert soil surrounding the chaparral plant and discourage growth by other plant species, thus effectively reducing competition for water and nutrients.
Plant Part Used and Common Preparations
The leaves are ground into a powdered extract that can be brewed into tea, which was the form used by Native Americans for centuries to treat various conditions such as respiratory illness, chickenpox, snakebite, and arthritis pain. More recently, chaparral has been prepared as a botanical in pill forms as well as in salves for topical application and concentrated extracts to be brewed into tea.
2. Traditional and Historical Use
Native American Traditions
Chaparral has been used for thousands of years by Native Americans for a variety of purposes. It has been employed primarily in tea form to help with cramping pains, joint pains, and allergic problems, as well as to eliminate parasites. Externally it has been applied to reduce inflammation and pain, and to promote healing of minor wounds.
The Pima, Yaqui, Maricopa, and Seri tribes have used various extracts and preparations from this plant to treat a wide variety of disorders. The leaves can be used in a bath for chickenpox or rheumatism, while a decoction made from the boiled leaves is used as a poultice for skin sores. Skin sores can also be treated with a powder made from dried leaves and stems. The leaves can be used to make a tea (chaparral tea) that is used to treat many disorders including cancer, venereal disease, tuberculosis, colds, and rheumatism.
The Pima brewed its leaves into teas to treat colds and digestive issues, while the Tohono O'odham used it topically for wounds and skin irritations. The Apache valued it for rheumatism and kidney stones, often preparing salves or infusions.
The Pima, Navajo, and Cahuilla peoples documented diverse applications, from addressing skin conditions and joint discomfort to serving as a spiritual cleanser before significant life transitions.
Folk Medicine in Mexico and the Broader Southwest
Tea made from the leaves of Larrea tridentata has long been used in folk medicine to treat digestive disorders, rheumatism, venereal disease, sores, bronchitis, chickenpox, and the common cold. The desert plant creosote bush has been used by Native Americans to treat a variety of ailments including infertility, arthritis, diabetes, gallbladder and kidney stones, and inflammation.
Creosote bush has been used in traditional medicine to treat more than 50 illnesses. Most common uses are associated with diseases of renal and gynecologic origins.
Ceremonial and Spiritual Uses
For generations, Indigenous desert communities used chaparral in contexts far beyond personal wellness. Leaves were crushed into poultices for wounds, prepared for a range of traditional conditions, and burned in smoke form for spiritual purification and protection during ceremonies.
Historical Use in Western Herbalism
Larrea tridentata (chaparral) enjoys use as a nutritional supplement, weight-loss medication, anticancer agent, general cleansing tonic, and as a remedy for arthritis in folk medicine. Interest in chaparral as a dietary supplement gained momentum in the mid-20th century in the United States, when it was available in health food stores primarily as a loose-leaf tea, capsule, or tablet, before FDA safety concerns prompted voluntary withdrawal from the market by many manufacturers in the early 1990s.
3. Chemical Constituents and Composition
Overview of the Leaf Resin
The natural products on the surface of the Larrea tridentata leaves — the leaf resin — constitutes approximately 10–15% of the dry weight of the leaves and is composed of approximately 50% nordihydroguaiaretic acid (NDGA) and related lignans, and 50% flavonoids. Larrea tridentata is a notable source of natural products, with approximately 50% of the leaves' dry weight as extractable matter.
Nordihydroguaiaretic Acid (NDGA) — The Principal Constituent
Chaparral extracts have multiple active ingredients, the most prominent being nordihydroguaiaretic acid (NDGA), which has potent antioxidant properties. NDGA, a phenolic compound, is the active ingredient of creosote bush; it is found in high concentrations in the leaves and twigs of this shrub. A study on the distribution of secondary phenolic compounds reported that flowers, leaves, green stems, and small woody stems all contained NDGA, with highest concentrations in leaves (38.3 mg/g) and green stems (32.5 mg/g).
NDGA constitutes 5–10% of the leaves' dry weight. NDGA presents two catechol rings that confer a very potent antioxidant activity by scavenging oxygen free radicals, and this may explain part of its therapeutic action.
Other Lignans
Other secondary metabolites identified in L. tridentata include lignans (dihydroguaiaretic acid, hemi-norisoguaiacin, and norisoguaiacin), flavonoids (aglycones: apigenin and kaempferol; glycosides: chrysoeriol and quercetin), saponins (larreagenin A and larreic acid), triterpenes, and triterpenoids, among others.
Flavonoids
The resin that covers the leaves yielded 19 flavonoid aglycones, as well as several lignans, notably including the antioxidant NDGA. The flavonoids function as antimicrobial agents and as protection against herbivores, UV radiation, and water loss, and are potentially important in the species' success in desertic environments.
Additional Compound Classes
The plant also contains triterpene saponins, volatile terpenoids, sterols, and lipids. Some glycosylated flavonoids, sapogenins, essential oils, halogenic alkaloids, and waxes were isolated from creosote bush.
NDGA Quinone — A Metabolic Concern
The active constituent of chaparral has been identified as nordihydroguaiaretic acid with O-quinone as its major metabolite. O-quinone is believed to increase fragility of lysosomal membranes by inducing lipid peroxidation, causing autolysis, desquamation of necrotic proximal tubular epithelial cells, and accumulation of cellular debris leading to tubular obstruction. NDGA quinone is found in chaparral (Larrea tridentata) and is suspected to be a causative agent of the toxic effects associated with consumption of chaparral products.
4. Established Mechanisms of Action
Free-Radical Scavenging and Antioxidant Activity
The best-characterized effects of NDGA are: (1) the ROS-scavenging nature of NDGA decreases the pro-oxidant effects of inflammation; (2) the inhibitory effects on lipoxygenase (LOX) activity, leading to the reduction of lipid hydroperoxides that trigger oxidative stress due to their decomposition to free radicals; and (3) the activation of endogenous antioxidant responses mediated by NRF2.
The strong antioxidant properties may be due to the presence of four reducing equivalents from the two catechol groups in NDGA; hydrogen atoms of the four phenolic hydroxyl groups react with reactive oxygen species.
Lipoxygenase Inhibition
NDGA has been proven to selectively inhibit arachidonic acid 5-lipoxygenase activity, which reduces leukotriene and prostaglandin synthesis, thus leading to a reduction of inflammatory pathways. NDGA maintains iron in the Fe²⁺ form, hence breaking the redox cycle of lipoxygenases and resulting in their inactivation.
Nordihydroguaiaretic acid (NDGA) is a dicatechol and phytochemical polyphenolic antioxidant and an established inhibitor of human arachidonic acid 5-lipoxygenase (LOX) and 15-LOX.
NRF2 Pathway Activation
Additional effects of NDGA include inhibition of lipoxygenases and activation of signaling pathways that impinge on the transcription factor Nuclear Factor Erythroid 2-related Factor (NRF2), a master regulator of endogenous cellular antioxidant defense.
Effects on Lipid Metabolism and Metabolic Pathways
NDGA functions as a potent ligand or proligand for and activator of PPARα (either directly or indirectly through its actions as a lipoxygenase inhibitor), which suggests that it most likely stimulates LXR and ChREBP pathways involved in lipid metabolism.
Cytochrome P450 Inhibition
NDGA blocks the activity of cytochrome P450, an enzyme that metabolizes many medications, and therefore may increase the risk for toxicity from co-administered drugs.
Antiplatelet Activity
Because NDGA inhibits platelet aggregation, there is a potential increased risk for bleeding in people taking anticoagulants, antiplatelet drugs, or supplements with these properties.
5. Scientific Evidence by Area of Use
5.1 Antioxidant / Free-Radical Scavenging
Evidence level: Robust in vitro; limited clinical evidence.
L. tridentata has long been established as a powerful antioxidant through the effects of one of its predominant constituents, nordihydroguaiaretic acid (NDGA). Nordihydroguaiaretic acid has been shown to exert protective properties in cases of ferric-nitrilotriacetate-induced renal and hepatic toxicities; the protective nature of NDGA appears attributable to its antioxidant activities. These findings are from animal and cell-culture models; controlled human trials evaluating antioxidant outcomes specifically from whole chaparral preparations are lacking.
5.2 Anti-inflammatory / Arthritis
Evidence level: Preclinical; traditional use is well documented; robust human data are absent.
Scientific research has revealed beneficial effects of Larrea tridentata — including antioxidant, antitumor, neuroprotective, regenerative, antibacterial, antiviral, antifungal, anthelmintic, antiprotozoal, and insecticidal properties — although reports indicate that some compounds may be hepatotoxic and nephrotoxic.
The inhibition of 5-lipoxygenase and the consequent reduction in leukotriene synthesis provides a plausible mechanistic basis for anti-inflammatory effects. LOX inhibitors are currently being investigated as treatments for cancers, coronary artery disease, and asthma. However, no published randomized controlled trials in human subjects specifically evaluating chaparral (as the whole plant extract) for arthritis or general inflammation have been identified in the peer-reviewed literature at the time of this writing.
5.3 Cancer
Evidence level: Preclinical evidence (in vitro and animal models) only for the crude extract. A single early-phase clinical trial exists for isolated NDGA in prostate cancer. A synthetic NDGA derivative (terameprocol) has entered clinical trials with limited outcomes reported. No evidence supports the use of whole chaparral extract as an anticancer agent in humans.
Although lab studies suggest an active compound in chaparral, nordihydroguaiaretic acid (NDGA), has antiviral, anticancer, and antiparasitic properties, a clinical trial found chaparral was ineffective as an anticancer agent.
In preclinical settings, NDGA blocked cellular respiration in vitro and inhibited the growth of estrogen receptor (ER) positive MCF-7 cells that overexpressed HER2 (MCF-7/HER2-18), with additive effects when combined with tamoxifen. NDGA was found to inhibit 5-lipoxygenase activity in an adenocarcinoma cell line and additionally inhibited non–small cell lung cancer (NSCLC) growth and reduced colony numbers. The anticancer effects of a crude extract containing L. tridentata were assessed in invasive breast cancer cell lines; L. tridentata was found to inhibit the growth of MCF-7/AZ breast cancer cells as well as decrease the phosphorylation levels of extracellular signal-regulated kinase (ERK) 1 and 2.
In the only human study specifically examining NDGA as an anticancer agent, one pilot study in patients with relapsed prostate cancer suggested NDGA was reasonably well tolerated and affected increases in PSA doubling time, but it was also associated with transaminitis in some patients. In a phase II clinical trial in prostate cancer patients, NDGA (2,000 mg/day orally) was generally well tolerated, but some adverse events included nausea/vomiting, diarrhea, syncope, and elevated liver function tests.
Regarding the derivative terameprocol: Tetra-O-methyl NDGA, or terameprocol (TMP), has been shown to inhibit the growth of certain tumor-derived cell lines and entered clinical trials for the treatment of human cancer. Terameprocol selectively inhibits Sp1 and Sp1-dependent cyclin-dependent kinase (Cdc2), survivin, and vascular endothelial growth factor (VEGF) expression, and induces growth arrest and apoptosis. Terameprocol entered Phase I/II clinical trials in patients with recurrent high-grade lymphoma or advanced forms of leukemia, but proved not to have sufficient efficacy to advance further in those indications. High concentrations of NDGA are required to inhibit tumor growth, thus yielding toxicity; therefore, an intensive search has been made to develop NDGA analogs with low toxicity.
A clinical study looking at chaparral tea and NDGA in advanced, incurable cancer patients showed no evidence of hepatotoxicity; limitations of this study included a lack of detail on those who did not complete the trial (25 percent of the subjects).
5.4 Antimicrobial, Antiviral, and Antifungal Properties
Evidence level: Predominantly in vitro; no controlled human clinical trials for antimicrobial indications.
Among several valuable bioactive phenolic compounds found in this plant, the naturally occurring lignan NDGA has been pointed out as the most important, since it presents biological activities of large interest in the health area, such as antiviral, antimicrobial, and antitumorigenic. Some studies have demonstrated antimicrobial capacity of extracts from L. tridentata, including antiviral, antifungal, and antibacterial activities.
NDGA appears to be responsible for exerting antimicrobial effects. It has been shown to inhibit viruses such as HIV, HPV, herpes simplex virus, and influenza virus. Other microorganisms that an ethanolic extract of L. tridentata was documented to inhibit include Microsporum canis, M. gypseum, Trichophyton tonsurans, Epidermophyton floccosum, Sporothrix schenckii, Nocardia asteroides, N. brasiliensis, Shigella dysenteriae, Yersinia enterocolitica, Listeria monocytogenes, Proteus vulgaris, and Clostridium perfringens.
Regarding HIV, NDGA and other antioxidants have been shown to be potent inhibitors of the human immunodeficiency virus type 1 (HIV) transcription. The mode of action of this anti-HIV activity was suggested to be due to the potent antioxidant activity of NDGA inhibiting a redox-regulated signal transduction pathway leading to production of HIV virus. Derivatives of NDGA have been shown to inhibit the production of human immunodeficiency virus, herpes simplex virus, and human papillomavirus. In vitro, this appears to occur because of disruption of the activities of the Sp1 transcription factor. All such antimicrobial findings are from laboratory studies; human clinical evidence is absent.
5.5 Metabolic Effects (Dyslipidemia and Insulin Resistance)
Evidence level: Animal studies only; no human clinical trials.
Creosote bush-derived NDGA, a lipoxygenase inhibitor, possesses antioxidant properties and functions as a potent antihyperlipidemic agent in rodent models. In ob/ob mice, feeding with either low (0.83 g/kg diet) or high-dose (2.5 g/kg diet) NDGA for 16 weeks significantly improved plasma triglyceride (TG), inflammatory chemokine levels, hyperinsulinemia, insulin sensitivity, and glucose intolerance. NDGA treatment caused a marked reduction in liver weight and TG content while enhancing rates of fatty acid oxidation. Microarray analysis of hepatic gene expression demonstrated that NDGA treatment altered genes for lipid metabolism, with genes involved in fatty acid catabolism most significantly increased. These results have not been replicated in human trials.
5.6 Neuroprotection
Evidence level: Preclinical (animal models) only; no human data.
In murine models, NDGA exerted neuroprotective effects against ischemic/reperfusion injury mediated via suppression of the c-Jun N-terminal protein kinase pathway, and ameliorated potassium dichromate-induced oxidative stress and nephrotoxicity. Neuroprotective benefit reflects only preclinical evidence, which is mixed for mechanisms of action. Brain penetrance is likely low. Human research to suggest benefits to patients with dementia: none available.
5.7 Skin and Topical Applications
Evidence level: Traditional use is extensive; laboratory evidence provides plausible mechanisms; controlled human trials for topical use are lacking.
Chaparral has been used topically for skin rashes, acne, minor wounds, and general skin irritation. The combination of antioxidant, anti-inflammatory, and antimicrobial properties observed in lab tests provides a reasonable explanation for why it might soothe irritated skin or support wound healing. Traditional preparations involved applying a poultice or wash made from the leaves directly to the affected area. Of all the ways chaparral has been used, topical application is the least controversial from a safety standpoint, since it avoids the liver exposure that makes internal use risky.
6. Dosage Forms and Reported Dosages
The leaves are ground into a powdered extract that can be brewed into tea, which was the form used by Native Americans for centuries. More recently, chaparral has been prepared as a botanical in pill forms as well as in salves for topical application and concentrated extracts to be brewed into tea.
Chaparral tea has traditionally been prepared with 1 teaspoon of chaparral leaves or flowers steeped in 1 pint of water for 15 minutes.
For internal tincture preparations, one source reports: less than 1 mL daily of tinctures containing less than 10% chaparral for internal consumption.
In the prostate cancer phase II clinical trial cited above, NDGA was administered at 2,000 mg/day orally.
Chaparral's most significant drawback is its documented ability to cause liver damage. Reports of hepatotoxicity have been linked to oral doses of the crude herb ranging from 1.5 to 3.5 grams per day.
Although the pure form of NDGA is not commercially available, chaparral (extract of the creosote bush) is sold as herbal supplements in aqueous extract, tea bags, capsules, and tablets.
7. Safety: Hepatotoxicity and Other Adverse Effects
Documented Hepatotoxicity Cases
Of 18 reports of illnesses associated with the ingestion of chaparral, there was evidence of hepatotoxicity in 13 cases. Clinical presentation, characterized as jaundice with a marked increase in serum liver chemistry values, occurred 3 to 52 weeks after the ingestion of chaparral, and it resolved 1 to 17 weeks after most individuals stopped their intake of chaparral. The predominant pattern of liver injury was characterized as toxic or drug-induced cholestatic hepatitis; in 4 individuals, there was progression to cirrhosis; and in 2 individuals, there was acute fulminant liver failure that required liver transplants.
These data indicate that the use of chaparral may be associated with acute to chronic irreversible liver damage with fulminant hepatic failure, and they underscore the potential for certain dietary supplement ingredients to cause toxic effects on the liver.
There are nine reported cases of definite hepatotoxicity temporally related to chaparral use as a single known agent; there are an additional six cases of possible hepatotoxicity.
The product used by one patient was examined using microscopic and chromatographic analysis and was correctly identified as Larrea tridentata with no evidence of biochemical or biological contamination. The severity of the liver damage in these case reports does not seem to correlate directly with either the amount of chaparral consumed or the duration of use.
There are five cases with documented recovery from liver damage after cessation of chaparral use. There is one case documenting a return of jaundice following resumption of chaparral ingestion.
Mechanism of Hepatotoxicity
The component of chaparral leaf extracts that is responsible for hepatotoxicity is not known; features of the disease suggest that the liver injury is idiosyncratic rather than a direct toxic effect. NDGA causes inhibition of the mitochondrial electron transport chain. There are some similarities between acetaminophen (NAPQI) toxicity and NDGA toxicity that can be used to hypothesize a mechanism of hepatotoxicity based on the formation of an NDGA quinone.
As with other reported herbal toxicities, the liver injury attributed to chaparral may have been due to contaminants or improperly prepared extracts. Hepatotoxicity from chaparral is rare, but some cases have been severe, leading to acute liver failure.
Renal Toxicity
Chaparral has long been associated with cystic renal disease in both rats and humans. One may hypothesize that chaparral ingestion would lead to toxicity in the kidney if chaparral toxicity is related to NDGA metabolism to a toxic quinone, which is purely theoretical. Indeed, renal toxicity of NDGA is evident in animal studies. NDGA causes lymphatic and renal lesions when given chronically in high doses to rodents.
Capsule vs. Tea Formulations
There have been sporadic reports of people developing liver or kidney problems after taking chaparral, particularly in capsules. Almost all of these cases involved either the use of capsules or excessive amounts of tea. Some of these cases were people with established liver disease prior to using the herb. Tea and tincture of chaparral have an extremely strong taste considered disagreeable by most people, which restricts the amount they can tolerate before feeling nauseous. Capsules bypass this protective mechanism and should therefore be avoided.
Inconsistencies in the Safety Evidence
Reportedly, native populations in the southwestern United States have used chaparral tea for decades without evidence of toxicity. In addition, a clinical study looking at chaparral tea and NDGA in advanced, incurable cancer patients showed no evidence of hepatotoxicity. Of the 59 treated patients, no pattern of hepatotoxicity was reported following consumption of either chaparral tea or NDGA by the terminally ill cancer patients. This inconsistency has not been fully resolved in the literature.
Regulatory Status
NDGA, formerly employed as a food additive in low concentrations, has been removed by the FDA from its "Generally Recognized as Safe" (GRAS) substances list. The FDA has issued consumer advisories regarding internal use of chaparral.
8. Drug Interactions and Contraindications
Because NDGA inhibits platelet aggregation, there is a potential increased risk for bleeding in people taking anticoagulants, antiplatelet drugs, or supplements with these properties. An increased risk for toxicity is expected in people taking renal or hepatotoxic medications.
NDGA blocks the activity of cytochrome P450, an enzyme that metabolizes many medications, and therefore may increase the risk for toxicity from co-administered drugs.
An increased risk for toxicity is expected in people taking renal or hepatotoxic medications.
9. Body Systems and Health Areas of Association
- Hepatic system: Chaparral leaf extracts affect multiple intrahepatic pathways, including those involving cyclooxygenases and lipoxygenases; liver toxicity is the primary documented risk.
- Renal system: Long-standing association with cystic renal disease in both rats and humans.
- Musculoskeletal/articular system: Traditional use for rheumatism and arthritis; in vitro anti-inflammatory mechanisms identified.
- Dermatologic system: Traditional and contemporary topical use for wounds, skin infections, and rashes.
- Respiratory system: Traditional use for colds, bronchitis, and tuberculosis; a tea made from the leaves is used to treat many disorders including tuberculosis and colds.
- Cardiovascular and metabolic systems: NDGA has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases.
- Neurological system: Animal-model evidence of neuroprotective properties; no human data.
- Oncology: Extensive preclinical study; limited and inconclusive human data for both the crude extract and NDGA.
- Immune and infectious systems: Documented in-vitro activity against a broad range of bacteria, fungi, and viruses, including HIV, HSV, HPV, and influenza.
References
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