cin,4,56,3^0 -di-O-demethylisoguaiacin (previ-
ously designated 3^0 -hydroxynorisoguaiacin),
6-O-demethylisoguaiacin (norisoguaiacin),
didehydro-3^0 -demethoxy-6-O-demethylgu-
aiacin, 3^0 -demethoxy-6-O-demethylguaia-
cin,^6 4-epi-larreatricin, larreatricin, 3^0 ,3^00 -di-
methoxylarreatricin, 3,4-dehydrolarreatricin,
larreatridenticin, and others;^7 flavonoids in-
clude 2,6-di-C-glucopyranosylapigenin, 6,8-
di-C-glucopyranosylchrysoeriol, gossypetin
3,7-dimethyl ether, 5,8,4^0 -trihydroxy-3,7,3^0 -
trimethoxyflavone,^8 quercetin, kaempferol,
rhamnetin, rutin;^9 triterpenes, including
larreagenin A, larreic acid, erythrodiol-3-b-
(4-hydroxy-cinnamdyl), erythrodiol-3-b-(4-
dihydroxy cinnamdyl); essential oil contains
a-pinene,D-3-carene, limonene, camphene,
linalool, borneol, camphor, bornyl acetate,
etc.9–11
PHARMACOLOGY AND BIOLOGICAL
ACTIVITIES
Uterine relaxation activityin vitroled to the
isolation of an antiimplantation agent from
the leaves and twigs (3^0 -demethoxyisoguaia-
cin).6,12Larrea tridentataextracts have also
shownin vitroantimicrobial,^13 antioxidant,^14
and hepatic enzyme-inhibiting activity.^11
In vitrostudies have shown that NDGA
induces apoptosis in various human and ani-
mal cancer cell lines15,16and cell growth of
estrogen-positive human breast cancer cells
(MCF-7).^17 Among other activities, it also
inhibits platelet aggregation,^18 testosterone
release,^19 insulin secretion,^20 human lipoxy-
genases,^21 and from topical application, skin
tumor formation in rodents.^22
A clinical trial of chaparral tea (16–24
oz./day) in patients with advanced malignan-
cies found a significant number appeared to
show tumor progression.^23
TOXICOLOGY
At high doses (580 mg/kg p.o.), solvent ex-
tracts of the leaves and twigs and of the stems
have shown antifertility effects in pregnant
rats. Behavioral and reproductive organ tox-
icity was shown in male hamsters (water/
ethanol extract of dried leaves at 4% of diet).
Fed to chicks (3 weeks old) at 5% of the diet,
the ground leaves resulted in body weight-
gain inhibition, but not at 2.5% of the feed.
In vitrotests found cytotoxicity in human and
rat kidney and liver slices (ethanol/water tinc-
ture) and in primary rat hepatocytes (water,
ethanol/water tincture, and various solvent
extracts).^11 Chaparral tea was only weakly
cytotoxic to rat hepatocytesin vitro.^24
Contact dermatitis fromLarreaspecies is
common (DE SMET ET AL). Case reports of liver
toxicity in subjects largely taking chaparral
orally in tablets or capsules (alone or in com-
bination with other substances)25–28are con-
founded by a lack of hepatotoxicity from
chaparral or NDGA in animal studies, poor
characterization of the ‘‘chaparral’’ taken,
possible pre-existing liver disease, and other
factors.^11 In a retrospective clinical study,
small amounts of a tincture of the leaves and
flowers (water/ethanol extract) as part of a
more complex herbal preparation (8–10 other
herbs) taken by patients over 2 years appeared
to be safe. Topical use of chaparral inRicinus
oil also appeared to be safe.^29
NDGA was extensively used as a food
antioxidant from 1943 to 1968. It was re-
moved from GRAS status after a chronic
feeding study in rats (0.5–1% NDGA for 74
weeks) found lymph node and kidney
lesions.^11USESMedicinal, Pharmaceutical, and Cosmetic.
NDGA is approved for use in topical form in
the U.S. in the treatment of skin cancer, psori-
asis, and actinic keratosis.^11Food. NDGA was formerly used as an anti-
oxidant in numerous food products (0.02%);
currently, use is permitted only in animal fat
products (lard, animal shortenings at 0.01%)
under USDA authority (TYLER3).^11Chaparral 175