Larrea tridentata

 

Larrea tridentata 

Synonyms

No documentation

Vernacular Name

Chaparral, Larrea mexicana, Creosote bush, Greasewood, Jarillo, Hediondilla and Gobernadora.[1],[2],[3],[4],[5]

Description

The use of Larrea tridentate or chaparral is ubiquitous throughout the southwestern United States and northern Mexico.[6],[7] The leaves and twigs of the creosote bush have been collected and used to prepare herbal teas for centuries, dating back to ancient times.[8] Ethnopharmacological studies have shown L. tridentata to be effective in the treatment of arthritis, pain, inflammation, diabetes, gastrointestinal disorders, and cancer when used in low doses, for a short duration of time, and when obtained through a reputable naturopathic clinic.[9],[10],[11]

L. tridentata plant growth is so dense that it is often impenetrable even to wildlife. This shrub grows to just over one meter and is a sclerophyllous, or hard-leaved, plant. The hard leaves roll up, under and fall off during the summer season. The plant has the ability to regenerate from a burned stump left after a wildfire.

Origin / Habitat

L. tridentate is native to the southern California area and is also found in Mexico, the Mediterranean, South Africa and parts of South America and Australia. This shrub-like evergreen needs hot dry summers and mild winters to survive. It also benefits from wildfires as are common in California. The leaves and twigs of the L. tridentata have been collected and used to prepare herbal teas for centuries, dating back to ancient times. This plant has often been miss-classified.

Chemical Constituents

-Lignans (nordihydroguaiaretic acid, dihydroguaiaretic acid, etc.)
-Flavonoid glycosides (apigenin methyl ester quercetin, dimethoxyl morin, etc.)
-Protein (amino acids)
-Carbohydrates (dextrin, glucose, sucrose)
-Vitamins (vitamin C, carotenoids).[14],[15],[16]

L. tridentata also contains triterpene saponins, volatile terpenoids, sterols and lipids. The function of these constituents within the medicinal properties associated with L. tridentata is unknown.[17],[18]

Plant Part Used

Leaves and twigs of the plant traditionally used to prepare a tea; capsules/tablets and tinctures available for commercial use.[12]

Medical Uses

General

Treatment of pain and inflammation, arthritis, diabetes, prevention and elimination of gallbladder and kidney stones.[19],[20],[21]

 

Antimicrobial[22], Anticancer[23]

 

Most Frequently Reported Uses

Treatment of pain and inflammation, arthritis, diabetes, prevention and elimination of gallbladder and kidney stones.[24],[25],[26]

Dosage

Dosage Range

Due to potential toxicity of this herb, it is inadvisable to consider a range of dosage levels.

Most Common Dosage 

Less than 1 mL daily of tinctures containing less than 10% L. tridentata for internal consumption.[13]

 

Standardized to 

No known standardization.

Pharmacology

Pre-clinical

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.[27],[28] However, NDGA conveys numerous pharmacologic activities onto L. tridentata and is also recognized as an inhibitor of lipoxygenase.[29] Through inhibition of lipoxygenase and inference with the arachidonic acid cascade, NDGA interrupts the formation of leukotrienes. Inhibition of leukotriene formation produces anti-inflammatory effects; the anti-inflammatory effects of NDGA are associated with improvement in inflammatory disorders (e.g. arthritis).[30]

The animal studies have shown NDGA to be effective in the treatment of type II diabetes as well. Mouse models of type II diabetes have displayed reduced plasma glucose concentrations following treatment with NDGA despite the fact that plasma insulin concentrations remained unchanged.[31] In this animal model of type II diabetes, treatment with NDGA improved glucose tolerance through an accentuation of the ability of insulin to reduce plasma glucose concentrations.[32] Furthermore, rat models of type II diabetes have shown NDGA to be effective in reducing plasma glucose and triglyceride concentrations.[33]

The effects of NDGA reported in the diabetic studies may explain the ability of NDGA to prevent and even eliminate gallbladder and kidney stones. In traditional Mexican medicine, L. tridentata has been reported to be used in the treatment of gallbladder and kidney stones.[34] While findings have been conflicting, some studies have reported a greater incidence of gallstones in patients suffering from type II diabetes when compared to non-type II diabetic patients.[35],[36],[37] If the association between diabetes and gallstone formation is shown to be causational rather than correlational, L. tridentata use may prevent or eliminate gallstones through its anti-diabetic actions. Finally, when administered to hamsters, an ethanolic extract of L. tridentata was associated with a modification of the bile acid profile and a reduction in moles percent cholesterol, indicating an increased solubility of cholesterol in bile.[38] The authors concluded that these properties of the ethanolic extract of L. tridentata were responsible for preventing and eliminating cholesterol gallstone formation.[39]

While its anti-inflammatory actions indicate usefulness in the treatment of inflammatory conditions such as arthritis, the immunomodulatory effects of L. tridentata appear to be inclusive of antimicrobial and antitumor activity as well. Extracts from L. tridentata have shown it to possess antimicrobial activity against a spectrum of microbial organisms, including but not limited to L. monocytogenes, C. perfringens, S. dysenteriae, Y. enterocolitica, P. vulgaris, actinomycetes and molds.[40] Recent studies have further supported its use to treat several bacterial (e.g. H. pylori and tuberculosis) and fungal infections.[41],[42],[43] Several derivatives of NDGA have been examined and evidence suggests that three derivates (Mal.4, M(4)N, and tetra-acetyl NDGA) inhibit gene expression of type 16 of the human papillomavirus.[44] As infection with human papillomaviruses (HPV) is known to cause cervical cancer in infected individuals, the antimicrobial activity of NDGA derivatives may help prevent onset of cervical cancer in HPV patients.

L. tridentata has been investigated for use in the treatment of cancer as a result of the anti-tumor actions exhibited by its predominant constituent, NDGA. Extracts of L. tridentata have been shown to decrease the growth of breast cancer cells.[45],[46] NDGA has been shown to inhibit ligand activation of the insulin-like growth factor I (IGF-I) receptor in breast cancer cells.[47] By disrupting the phosphorylation process, activation of the IGF_I receptor is inhibited and so are the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase signaling pathways normally induced when the IGF_I receptor is activated.[48] In addition to its effects on breast cancer cells, NDGA has been shown to inhibit the growth of neuroblastoma cells and to induce apoptosis in a dose-dependent fashion in neuroblastoma cells.[49] These results are attributed, at least in part, to the inhibition of IGF-I activation of the IGF-I receptor and disruption of the associated signaling pathways.[50],[51] The antitumor effects of NDGA do not appear to be limited to breast cancer or neuroblastoma; a study in gerbils has shown NDGA to be effective in decreasing the incidence of H. Pylori-associated gastric adenocarcinomas and NDGA is currently in Phase II of the clinical trial process for treatment of non-metastatic recurrent prostate cancer.[52],[53] Finally, one derivative of NDGA (3’-O-methyl-nordihydroguaiaretic acid) has been shown to induce apoptosis in cervical tumor cells.[54] The ability of NDGA derivatives to both inhibit gene expression of certain types of the human papillomavirus while also inducing apoptosis in cervical cancer cells indicates that extracts of L. tridentata may be able to alter the course of viral-induced carcinogenesis.

Clinical

No documentation

Interaction and Depletions

Interaction with other Herbs

No documentation

Interaction with Drugs

-Antirheumatoid agents
-Lipoxygenase Inhibitors
-Hypoglycemic agents
-Cholesterol-lowering agents
-Anticoagulant agents
-Antiplatelet agents
-Non-steroidal anti-inflammatory agents
-Antimicrobial agents
-Interferon preparations
-Chemotherapeutic agents
-Antiarrhythmic agents
-Anti-seizure agents
-Antituberculosis agents
-Agents with potential or established hepatotoxicity (e.g. alcohol, acetaminophen/paracetamol, naltrexone, phenothiazines, black cohosh etc.)

Precautions and Contraindications

Side effects

Patients who have a history of liver or kidney problems should not use L. tridentata. Patients should always inform their medical doctor about any herbal supplements and/or vitamins that the patient is taking.

There have been reports of hepatotoxicity and nephrotoxicity associated with L. tridentata use.[55],[56],[57] Specifically, cholestatic hepatitis has been reported following ingestion of L. tridentata with several patients showing progression to cirrhosis or liver failure requiring transplantation.[58] However, it must be considered that any herbal supplement or pharmaceutical medication may produce idiosyncratic reactions within a population that make a person more susceptible to the effects of a drug or alter the ability of the body to metabolize the drug.[59],[60] In addition, microbial contamination or adulteration by additional herbal products of the L. tridentata preparations used in patients displaying hepatotoxicity and nephrotoxicity must be considered as potential explanations.[61],[62],[63] One of the main constituents of L. tridentata, nordihydroguaiaretic acid, has been shown to inhibit enzymes such as peroxidase, alcohol dehydrogenase, succinate dehydrogenase, phospholipase A2, cytochrome P450, NADH-dehydrogenase, etc. and inhibition of such enzymes may have clinical implications.[64]

Pregnancy

Patients planning to become pregnant, are pregnant or breastfeeding should not use L. tridentata.

Age limitation

Due to the potential for toxicity, L. tridentata should not be used in infants, children, or in any other patients with impaired metabolism.   

Adverse reaction

No documentation

Read More

  1) Native American Herbs

References

  1. Brinker F. Larrea tridentate (DC) Coville (chaparral or creosote bush). British Journal of Phytotherapy. 1993;3:10-31.
  2. Heron S, Yarnell E. The safety or low-dose Larrea tridentata (DC) coville (creosote bush or chaparral): A retrospective clinical study. The Journal of Alternative and Complementary Medicine. 2001;7:175-185.
  3. Arteaga S, Andrade-Cetto S, Cardenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Journal of Ethnopharmacology. 2005;98:231-239.
  4. Yam-Canul P, Chirino YI, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Cruz C, Villanueva C, Pedraza-Chaverri J. Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food and Chemical Toxicology. 2008;46:1089-1096.
  5. United States Department of Agriculture: Natural Resources Conservation Service. 2009. The PLANTS Database. National Plant Data Center, Baton Rouge, LA 70874-4490 USA. Available from http://plants.usda.gov. [Accessed on 18 Feb 2009].
  6. Brinker F. Larrea tridentate (DC) Coville (chaparral or creosote bush). British Journal of Phytotherapy. 1993;3:10-31.
  7. Kay MA. Healing with Plants in the American and Mexican West. Tucson: The University of Arizona Press; 1996.
  8. Heron S, Yarnell E. The safety or low-dose Larrea tridentata (DC) coville (creosote bush or chaparral): A retrospective clinical study. The Journal of Alternative and Complementary Medicine. 2001;7:175-185.
  9. Kay MA. Healing with Plants in the American and Mexican West. Tucson: The University of Arizona Press; 1996.
  10. Arteaga S, Andrade-Cetto S, Cardenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Journal of Ethnopharmacology. 2005;98:231-239.
  11. Yam-Canul P, Chirino YI, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Cruz C, Villanueva C, Pedraza-Chaverri J. Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food and Chemical Toxicology. 2008;46:1089-1096.
  12. Arteaga S, Andrade-Cetto S, Cardenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Journal of Ethnopharmacology. 2005;98:231-239.
  13. Heron S, Yarnell E. The safety or low-dose Larrea tridentata (DC) coville (creosote bush or chaparral): A retrospective clinical study. The Journal of Alternative and Complementary Medicine. 2001;7:175-185.
  14. Brinker F. Larrea tridentate (DC) Coville (chaparral or creosote bush). British Journal of Phytotherapy. 1993;3:10-31.
  15. Heron S, Yarnell E. The safety or low-dose Larrea tridentata (DC) coville (creosote bush or chaparral): A retrospective clinical study. The Journal of Alternative and Complementary Medicine. 2001;7:175-185.
  16. Arteaga S, Andrade-Cetto S, Cardenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Journal of Ethnopharmacology. 2005;98:231-239.
  17. Brinker F. Larrea tridentate (DC) Coville (chaparral or creosote bush). British Journal of Phytotherapy. 1993;3:10-31.
  18. Heron S, Yarnell E. The safety or low-dose Larrea tridentata (DC) coville (creosote bush or chaparral): A retrospective clinical study. The Journal of Alternative and Complementary Medicine. 2001;7:175-185.
  19. Arteaga S, Andrade-Cetto S, Cardenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Journal of Ethnopharmacology. 2005;98:231-239.
  20. Rivero-Cruz I, Acevedo L, Guerrero JA, Martinez S, Bye R, Pereda-Miranda R, Franzblau S, Timmermann BN, Mata R. Antimycobacterical agents from selected Mexican medicinal plants. Journal of Pharmacy and Pharmacology. 2005;57:1117-1126.
  21. Yam-Canul P, Chirino YI, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Cruz C, Villanueva C, Pedraza-Chaverri J. Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food and Chemical Toxicology. 2008;46:1089-1096.
  22. Verastegui MA, Sanchez CA, Heredia NL, Garcia-Alvarado JS. Antimicrobial activity of extracts of three major plants from the Chihuahuan desert. Journal of Ethnopharmacology. 1996;52:175-177.
  23. Youngren JF, Gable K, Penaranda C, Maddux BA, Zavodovskaya M, Lobo M, Campbell M, Kerner J, Goldfine ID. Nordihydroguaiaretic acid (NDGA) inhibits the IGF-I and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. Breast Cancer Research and Treatment. 2005;94:37-46.
  24. Arteaga S, Andrade-Cetto S, Cardenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Journal of Ethnopharmacology. 2005;98:231-239.
  25. Rivero-Cruz I, Acevedo L, Guerrero JA, Martinez S, Bye R, Pereda-Miranda R, Franzblau S, Timmermann BN, Mata R. Antimycobacterical agents from selected Mexican medicinal plants. Journal of Pharmacy and Pharmacology. 2005;57:1117-1126.
  26. Yam-Canul P, Chirino YI, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Cruz C, Villanueva C, Pedraza-Chaverri J. Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food and Chemical Toxicology. 2008;46:1089-1096.
  27. Ansar S, Iqbal M, Athar M. Nordihydroguaiaretic acid is a potent inhibitor of ferric-nitrilotriacetate-mediated hepatic and renal toxicity, and renal tumor promotion in mice. Carcinogenesis. 1999;20:599-606.
  28. Yam-Canul P, Chirino YI, Sanchez-Gonzalez DJ, Martinez-Martinez CM, Cruz C, Villanueva C, Pedraza-Chaverri J. Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food and Chemical Toxicology. 2008;46:1089-1099.
  29. Luo J, Chuang T, Cheung J, Quan J, Tsai J, Sullivan C, Hector RF, Reed MJ, Mesazaros K, King SR, Carlson TJ, Reaven GM. Masoprocol (nordihydroguaiaretic acid): A new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata). European Journal of Pharmacology. 1998;346:77-79.
  30. Rang HP, Dale MM, Ritter JM, Gardner P. Pharmacology: Local hormones, inflammation and allergy. New York: Churchill Livingstone.
  31. Luo J, Chuang T, Cheung J, Quan J, Tsai J, Sullivan C, Hector RF, Reed MJ, Mesazaros K, King SR, Carlson TJ, Reaven GM. Masoprocol (nordihydroguaiaretic acid): A new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata). European Journal of Pharmacology. 1998;346:77-79.
  32. Luo J, Chuang T, Cheung J, Quan J, Tsai J, Sullivan C, Hector RF, Reed MJ, Mesazaros K, King SR, Carlson TJ, Reaven GM. Masoprocol (nordihydroguaiaretic acid): A new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata). European Journal of Pharmacology. 1998;346:77-79.
  33. Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Brignetti D, Luo J, Khandwala A, Reaven GM. Effect of masoprocol on carbohydrate and lipid metabolism in a rat model of type II diabetes. Diabetologia. 1999;42:102-106.
  34. Arteaga S, Carmona A, Luis J, Andrade-Cetto A, Cardenas R. Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile secretion in hamsters. Journal of Pharmacy and Pharmacology. 2005;57:1093-1099.
  35. Pazzi P, Scagliarini R, Gamberini S, Pezzoli A. Gall bladder motor function in diabetes mellitus [review]. Alimentary Pharmacology and Therapeutics. 2000;14:62-65.
  36. Arteaga S, Carmona A, Luis J, Andrade-Cetto A, Cardenas R. Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile secretion in hamsters. Journal of Pharmacy and Pharmacology. 2005;57:1093-1099.
  37. Saxena R, Sharma S, Dubey DC. Gallbladder disorder in type 2 diabetes mellitus cases. Journal of Human Ecology. 2005;18:169-171.
  38. Arteaga S, Carmona A, Luis J, Andrade-Cetto A, Cardenas R. Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile secretion in hamsters. Journal of Pharmacy and Pharmacology. 2005;57:1093-1099.
  39. Arteaga S, Carmona A, Luis J, Andrade-Cetto A, Cardenas R. Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile secretion in hamsters. Journal of Pharmacy and Pharmacology. 2005;57:1093-1099.
  40. Verastegui MA, Sanchez CA, Heredia NL, Garcia-Alvarado JS. Antimicrobial activity of extracts of three major plants from the Chihuahuan desert. Journal of Ethnopharmacology. 1996;52:175-177.
  41. Stege PW, Davincino RC, Vega AE, Casali YA, Correa S, Micalizzi B. Antimicrobial activity of acqueous extracts of Larrea divaricata Cav (jarilla) against Helicobacter pylori. Phytomedicine. 2006;13:724-727.
  42. Rivero-Cruz I, Acevedo L, Guerrero JA, Martinez S, Bye R, Pereda-Miranda R, Franzblau S, Timmermann BN, Mata R. Antimycobacterical agents from selected Mexican medicinal plants. Journal of Pharmacy and Pharmacology. 2005;57:1117-1126.
  43. Quiroga EN, Sampietro AR, Vattuone MA. In vitro fungitoxic activity of Larrea divaricata cav. Extracts. Letters in Applied Microbiology. 2004;39:7-12.
  44. Craigo J, Callahan M, Huang RC, DeLucia AL. Inhibition of human papillomavirus type 16 gene expression by nordihydroguaiaretic acid plant lignan derivatives. Antiviral Research. 2000;47:19-28.
  45. Youngren JF, Gable K, Penaranda C, Maddux BA, Zavodovskaya M, Lobo M, Campbell M, Kerner J, Goldfine ID. Nordihydroguaiaretic acid (NDGA) inhibits the IGF-I and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. Breast Cancer Research and Treatment. 2005;94:37-46.
  46. Van Slambrouck S, Daniels AL, Hooten CJ, Brock SL, Jenkins AR, Ogasawara MA, Baker JM, Adkins G, Elias EM, Agustin VJ, Constantine SR, Pullin MJ, Shors ST, Kornienko A, Steelant WFA. Effects of crude aqueous medicinal plant extracts on growth and invasion of breast cancer cells. Oncology Reports. 2007;17:1487-1492.
  47. Youngren JF, Gable K, Penaranda C, Maddux BA, Zavodovskaya M, Lobo M, Campbell M, Kerner J, Goldfine ID. Nordihydroguaiaretic acid (NDGA) inhibits the IGF-I and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. Breast Cancer Research and Treatment. 2005;94:37-46.
  48. Meyer GE, Chesler L, Liu D, Gable K, Maddux BA, Goldenberg DD, Youngren JF, Goldfine ID, Weiss WA, Matthay KK, Rosenthal SM. Nordihydroguaiaretic acid inhibits insulin-like growth factor signaling, growth, and survival in human neuroblastoma cells. Journal of Cellular Biochemistry. 2007;102:1529-1541.
  49. Meyer GE, Chesler L, Liu D, Gable K, Maddux BA, Goldenberg DD, Youngren JF, Goldfine ID, Weiss WA, Matthay KK, Rosenthal SM. Nordihydroguaiaretic acid inhibits insulin-like growth factor signaling, growth, and survival in human neuroblastoma cells. Journal of Cellular Biochemistry. 2007;102:1529-1541.
  50. Meyer GE, Chesler L, Liu D, Gable K, Maddux BA, Goldenberg DD, Youngren JF, Goldfine ID, Weiss WA, Matthay KK, Rosenthal SM. Nordihydroguaiaretic acid inhibits insulin-like growth factor signaling, growth, and survival in human neuroblastoma cells. Journal of Cellular Biochemistry. 2007;102:1529-1541.
  51. Van Slambrouck S, Daniels AL, Hooten CJ, Brock SL, Jenkins AR, Ogasawara MA, Baker JM, Adkins G, Elias EM, Agustin VJ, Constantine SR, Pullin MJ, Shors ST, Kornienko A, Steelant WFA. Effects of crude aqueous medicinal plant extracts on growth and invasion of breast cancer cells. Oncology Reports. 2007;17:1487-1492.
  52. Toyoda T, Tsukamoto T, Mizoshita T, Nishibe S, Deyama T, Takenaka Y, Hirano N, Tanaka H, Takasu S, Ban H, Kumagai T, Inana KI, Utsunomiya H, Tatematsu M. Inhibitory effect of nordihydroguaiaretic acid, a plant lignan, on Helicobacter pylori-associated gastric carcinogenesis in Mongolian gerbils. Cancer Science. 2007;98:1689-1695.
  53. Pharmacokinetic and efficacy study of nordihydroguaiaretic acid (NDGA) in non metastatic recurrent prostate cancer. 2009. National Institutes of Health. Available from http://clinicaltrials.gov/ct2/show/NCT00678015.
  54. Allen KL, Tschantz DR, Awad KS, Lynch WP, DeLucia AL. A plant lignan, 3’-O-methyl-nordihydroguaiaretic acid, suppresses papillomavirus E6 protein function, stabilizes p53 protein, and induces apoptosis in cervical tumor cells. Molecular Carcinogenesis. 2007;46:564-575.
  55. Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Archives of International Medicine. 1997;157:913-919.
  56. Lambert JD, Zhao D, Meyers RO, Kuester RK, Timmermann BN, Dorr RT. Nordihydroguaiaretic acid: Hepatotoxicity and detoxification in the mouse. Toxicon. 2002;40:1701-1708.
  57. Haller CA, Dyer JE, Ko R, Olson KR. Making a diagnosis of herbal-related toxic hepatitis. Western Journal of Medicine. 2002;176:39-44.
  58. Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Archives of International Medicine. 1997;157:913-919.
  59. Heron S, Yarnell E. The safety or low-dose Larrea tridentata (DC) coville (creosote bush or chaparral): A retrospective clinical study. The Journal of Alternative and Complementary Medicine. 7:175-185.
  60. Haller CA, Dyer JE, Ko R, Olson KR. Making a diagnosis of herbal-related toxic hepatitis. Western Journal of Medicine. 2002;176:39-44.
  61. Sheikh NM, Philen RM, Love LA. Chaparral-associated hepatotoxicity. Archives of International Medicine. 1997;157:913-919.
  62. Heron S, Yarnell E. The safety or low-dose Larrea tridentata (DC) coville (creosote bush or chaparral): A retrospective clinical study. The Journal of Alternative and Complementary Medicine. 7:175-185.
  63. Haller CA, Dyer JE, Ko R, Olson KR. Making a diagnosis of herbal-related toxic hepatitis. Western Journal of Medicine. 2002;176:39-44.
  64. Arteaga S, Andrade-Cetto S, Cardenas R. Larrea tridentata (Creosote bush), an abundant plant of Mexican and US-American deserts and its metabolite nordihydroguaiaretic acid. Journal of Ethnopharmacology. 2005;98:231-239.