Chapter 85
RUE
(Ruta graveolens L.)
HISTORY
In addition to the medicinal use of rue for analgesia and
inflammation, the use of this herb for defense against
witches and evil spells dates back to ancient Greece and
the Middle Ages.
BOTANICAL DESCRIPTION
Although the two most common Ruta species used for
herbal medicine are R. graveolens L. (common rue) and
R. chalepensis L. (fringed rue), other Ruta species (R.
corsica DC., R. montana L.) are also traditional herbal
treatments.
Common Name: Common Rue, Rue
Scientific Name: Ruta graveolens L.
Botanical Family: Rutaceae (rues, rutacées)
Physical Description: This evergreen shrub has bi- or
tripinnate, bluish-green leaves, which emit a strong,
disagreeable odor. The yellow flowers are about
1 cm (∼0.4 in.) in diameter with toothed petals that
appear from June to September.
Distribution and Ecology: Common rue is a native
species of southern Europe and northern Africa
that was introduced into North America after
the Spanish Conquests. Common locations for
this plant include moist fields, pastures, and
roadsides.
Medical Toxicology of Natural Substances, by Donald G. Barceloux, MD
Copyright © 2008 John Wiley & Sons, Inc.
EXPOSURE
Sources
The essential oil obtained by steam distillation of the
dry aerial parts of R. graveolens typically yields <1%
essential oil. Steam distillation of Italian rue (R. graveo-
lens) produced 0.74% yellowish essential oil with an
intense, penetrating odor.1 This yield compares with
about 4.5% following supercritical-fluid extraction of
common rue.2 Rue is also a seasoning for cooking and
a source of methyl nonyl ketone, which is used in soaps,
creams, and perfumes.
Medicinal Uses
Traditional
There are many traditional herbal uses for Ruta species
throughout the world. Fresh aerial parts of rue are a
traditional treatment for palpitations and circulatory
disorders in Taiwan.3 In Saudi Arabia, decoctions of the
aerial parts of rue are a traditional treatment for fever,
pain, rheumatism, and mental disorders.4 This plant is a
treatment for syncope, menstrual disorders, rheuma-
tism, and neuralgias in Ayurvedic medicine. Decoctions
of the roots of rue are traditional Chinese treatments
for snake and scorpion envenomations. The aqueous
extract of rue is an herbal treatment for fever in Africa.
Ruta species are common herbs used as emmenagogues
to initiate delayed menses, as abortifacients to terminate
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PART 3 MEDICINAL HERBS and ESSENTIAL OILS
pregnancies,5 and as a birth control method.6 In a retro-
spective study on the use of herbal infusions to induce
abortions, 86 cases were reported to the Montevideo
Poison Center between 1986 and 1999.7 Ruta species (R.
chalepensis L., R. graveolens L.) were an ingredient in
26 of the cases with Ruta species being the single plant
used in 12 cases. Rue also is used as an insect repellant
and antihelminthic.8
Current
Extracts of Ruta graveolens are experimental chemo-
therapeutic agents, but the efficacy of these agents has
not been established.9 Other experimental uses include
the treatment of parasitic infections.10
Regulatory Status
Most countries do not regulate the use of rue.
PRINCIPAL INGREDIENTS
Chemical Composition
Ruta species contain a variety of chemicals including
quinoline alkaloids (graveoline), acridone alkaloids,11
flavonoids, furanocoumarins (5-methoxypsoralen, 8-
methoxypsoralen),12 tannins, sterols, and terpene com-
pounds. Volatile components of aqueous extracts of
Ruta graveolens leaves, flowers, stems, foots, and fruits
include primarily oxygenated compounds, such as
ketones (2-undecanone), alcohols (2-undecanol), and
aliphatic acids (pentanoic, hexanoic, octanoic, nona-
noic).13 The composition of the essential oil varies with
plant part. Following subcritical (CO2) extraction, the
main constituents of the essential oil as measured by
capillary chromatography with nitrogen-phosphorus,
flame ionization, and mass selective detection were as
follows: leaves, 2-nonanone (8.9%); flowers, 2-undecan-
one (13.4%); stems, chalepensin [3-(α-,α-dimethylallyl)
psoralen,13%]; and roots, geijerene (19.3%).2 Gas chro-
matography/mass spectrometry (GC/MS) detected 38
compounds in a steam distillate of dry aerial parts of R.
graveolens with the primary constituents being 2-keto
compounds.1 Methyl nonyl ketone (undecan-2-one, RN:
112-12-9) and 2-nonanone (nonan-2-one, CAS RN: 821-
55-6) represented 46.8% and 18.8% of the hydrodistil-
late, respectively. Triterpenoid compounds accounted
for about 11% of the constituents with limonene, 1,8-
cineole, and α-pinene being the most common mono-
terpene compounds. Minor constituents included
octanoic acid, methyl salicylate, 2-decanone, and methyl
undecyl ketone (2-tridecanone). The ethyl acetate
extract of leaves from Ruta graveolens contains furano-
coumarin compounds (5-methoxypsoralen, 8-methoxy-
580
psoralen) and quinolone alkaloids (graveoline) with
8-methoxypsoralen being the strongest photoirritant.14
The biogenic precursor of these linear furanocoumarin
compounds is umbelliferone.15
Physiochemical Properties
Animal studies suggest that extracts of rue have bacte-
riostatic, antihelminthic, anti-inflammatory, antipyretic,
and analgesic properties.4,16 However, there are few
clinical data to support the use of this herb for any of
these purposes.
Mechanism of Toxicity
Most adverse reactions to the use of rue result from
photosensitization to the psoralen compounds, such as
bergapten (5-methoxypsoralen) and xanthotoxin (8-
methoxypsoralen) in the plant.
DOSE RESPONSE
Recommended doses for herbal preparations of Ruta
graveolens include one cup of boiling water poured over
1–2 teaspoons of dried herb or the ingestion of 0.5–1 g
dried herb 3 times daily. The development of allergic
contact dermatitis is a hypersensitivity reaction that is
not specifically dose-related. However, phytophototox-
icity is an irritant type of photodermatitis that requires
UV light and no prior sensitization. These dermal reac-
tions increase with increasing doses of irritants.
TOXICOKINETICS
There are few data on the toxicokinetics of the compo-
nents of rue extract.
CLINICAL RESPONSE
Rare case reports associate the use of rue with the
development of phytophotodermatitis on sun-exposed
portions of the face and extremities.17 Skin lesions
include the appearance of pruritic, erythematous, linear
macules,18 and acute vesiculobullous dermatitis19 within
6–48 hours of exposure to rue.20 These lesions are char-
acterized by linear erythema with sharp demarcation
between the lesion and unaffected skin. Potential com-
plications include changes in pigmentation and infected
bullae. Phytophotodermatitis occurs following exposure
to several Ruta species in addition to R. graveolens
including R. montana L. (mountain rue),21 R. corsica
(Corsican rue),22 and R. chalepensis (fringed rue).23,24
Postabortion sepsis with multiorgan failure is a potential
complication of the use of Ruta infusions for the induc-

tion of abortions.24 A case report associated the recent
consumption of a decoction of Ruta graveolens with the
development of dyspnea, bradycardia, renal dysfunction,
and hyperkalemia in a 78-year-old woman. She began the
decoction 1 day before development of dyspnea and 3
days before admission to an emergency department. A
causal connection between rue and her symptoms was
not established because of the presence of pre-existing
disease and the lack of serum drug concentrations of her
prescribed medications (i.e., bisoprolol, diltiazem).
DIAGNOSTIC TESTING
Methods for analyzing the constituents of extracts from
Ruta species include GC with nitrogen-phosphorus or
flame ionization detection,1,2 gas/liquid chromatogra-
phy,25 and GC/MS.13
TREATMENT
Treatment is supportive. Therapy for skin lesions
includes antihistamines, soothing baths to reduce pruri-
tus, and topical corticosteroid creams. Oral steroids
may be necessary for more severe cases of rue-induced
phytophotodermatitis. The use of soap and water, sun
screens, and avoidance of sun exposure for 48 hours
reduces the severity of phytophotodermatitis if initiated
before the appearance of skin lesions.
References
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gas-chromatographic analysis of the secondary metabo-
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2000;43:379–390.
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85 RUE
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