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Chapter 85

(Ruta graveolens L.)

In addition to the medicinal use of rue for analgesia and Sources
inflammation, the use of this herb for defense against
witches and evil spells dates back to ancient Greece and The essential oil obtained by steam distillation of the
the Middle Ages. 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
Although the two most common Ruta species used for common rue.2 Rue is also a seasoning for cooking and
herbal medicine are R. graveolens L. (common rue) and a source of methyl nonyl ketone, which is used in soaps,
R. chalepensis L. (fringed rue), other Ruta species (R. creams, and perfumes.
corsica DC., R. montana L.) are also traditional herbal
treatments. Medicinal Uses
Common Name: Common Rue, Rue Traditional
Scientific Name: Ruta graveolens L.
There are many traditional herbal uses for Ruta species
Botanical Family: Rutaceae (rues, rutacées) throughout the world. Fresh aerial parts of rue are a
Physical Description: This evergreen shrub has bi- or traditional treatment for palpitations and circulatory
tripinnate, bluish-green leaves, which emit a strong, disorders in Taiwan.3 In Saudi Arabia, decoctions of the
disagreeable odor. The yellow flowers are about aerial parts of rue are a traditional treatment for fever,
1 cm (∼0.4 in.) in diameter with toothed petals that pain, rheumatism, and mental disorders.4 This plant is a
appear from June to September. treatment for syncope, menstrual disorders, rheuma-
Distribution and Ecology: Common rue is a native tism, and neuralgias in Ayurvedic medicine. Decoctions
species of southern Europe and northern Africa of the roots of rue are traditional Chinese treatments
that was introduced into North America after for snake and scorpion envenomations. The aqueous
the Spanish Conquests. Common locations for extract of rue is an herbal treatment for fever in Africa.
this plant include moist fields, pastures, and Ruta species are common herbs used as emmenagogues
roadsides. to initiate delayed menses, as abortifacients to terminate

Medical Toxicology of Natural Substances, by Donald G. Barceloux, MD

Copyright © 2008 John Wiley & Sons, Inc.


pregnancies,5 and as a birth control method.6 In a retro- psoralen) and quinolone alkaloids (graveoline) with
spective study on the use of herbal infusions to induce 8-methoxypsoralen being the strongest photoirritant.14
abortions, 86 cases were reported to the Montevideo The biogenic precursor of these linear furanocoumarin
Poison Center between 1986 and 1999.7 Ruta species (R. compounds is umbelliferone.15
chalepensis L., R. graveolens L.) were an ingredient in
26 of the cases with Ruta species being the single plant Physiochemical Properties
used in 12 cases. Rue also is used as an insect repellant
and antihelminthic.8 Animal studies suggest that extracts of rue have bacte-
riostatic, antihelminthic, anti-inflammatory, antipyretic,
Current and analgesic properties.4,16 However, there are few
clinical data to support the use of this herb for any of
Extracts of Ruta graveolens are experimental chemo-
these purposes.
therapeutic agents, but the efficacy of these agents has
not been established.9 Other experimental uses include
Mechanism of Toxicity
the treatment of parasitic infections.10
Most adverse reactions to the use of rue result from
Regulatory Status
photosensitization to the psoralen compounds, such as
Most countries do not regulate the use of rue. bergapten (5-methoxypsoralen) and xanthotoxin (8-
methoxypsoralen) in the plant.
Chemical Composition
Recommended doses for herbal preparations of Ruta
Ruta species contain a variety of chemicals including graveolens include one cup of boiling water poured over
quinoline alkaloids (graveoline), acridone alkaloids,11 1–2 teaspoons of dried herb or the ingestion of 0.5–1 g
flavonoids, furanocoumarins (5-methoxypsoralen, 8- dried herb 3 times daily. The development of allergic
methoxypsoralen),12 tannins, sterols, and terpene com- contact dermatitis is a hypersensitivity reaction that is
pounds. Volatile components of aqueous extracts of not specifically dose-related. However, phytophototox-
Ruta graveolens leaves, flowers, stems, foots, and fruits icity is an irritant type of photodermatitis that requires
include primarily oxygenated compounds, such as UV light and no prior sensitization. These dermal reac-
ketones (2-undecanone), alcohols (2-undecanol), and tions increase with increasing doses of irritants.
aliphatic acids (pentanoic, hexanoic, octanoic, nona-
noic).13 The composition of the essential oil varies with TOXICOKINETICS
plant part. Following subcritical (CO2) extraction, the
main constituents of the essential oil as measured by There are few data on the toxicokinetics of the compo-
capillary chromatography with nitrogen-phosphorus, nents of rue extract.
flame ionization, and mass selective detection were as
follows: leaves, 2-nonanone (8.9%); flowers, 2-undecan- CLINICAL RESPONSE
one (13.4%); stems, chalepensin [3-(α-,α-dimethylallyl)
psoralen,13%]; and roots, geijerene (19.3%).2 Gas chro- Rare case reports associate the use of rue with the
matography/mass spectrometry (GC/MS) detected 38 development of phytophotodermatitis on sun-exposed
compounds in a steam distillate of dry aerial parts of R. portions of the face and extremities.17 Skin lesions
graveolens with the primary constituents being 2-keto include the appearance of pruritic, erythematous, linear
compounds.1 Methyl nonyl ketone (undecan-2-one, RN: macules,18 and acute vesiculobullous dermatitis19 within
112-12-9) and 2-nonanone (nonan-2-one, CAS RN: 821- 6–48 hours of exposure to rue.20 These lesions are char-
55-6) represented 46.8% and 18.8% of the hydrodistil- acterized by linear erythema with sharp demarcation
late, respectively. Triterpenoid compounds accounted between the lesion and unaffected skin. Potential com-
for about 11% of the constituents with limonene, 1,8- plications include changes in pigmentation and infected
cineole, and α-pinene being the most common mono- bullae. Phytophotodermatitis occurs following exposure
terpene compounds. Minor constituents included to several Ruta species in addition to R. graveolens
octanoic acid, methyl salicylate, 2-decanone, and methyl including R. montana L. (mountain rue),21 R. corsica
undecyl ketone (2-tridecanone). The ethyl acetate (Corsican rue),22 and R. chalepensis (fringed rue).23,24
extract of leaves from Ruta graveolens contains furano- Postabortion sepsis with multiorgan failure is a potential
coumarin compounds (5-methoxypsoralen, 8-methoxy- complication of the use of Ruta infusions for the induc-
85 RUE

tion of abortions.24 A case report associated the recent 8. Guarrera PM. Traditional antihelmintic, antiparasitic and
consumption of a decoction of Ruta graveolens with the repellent uses of plants in Central Italy. J Ethnopharmacol
development of dyspnea, bradycardia, renal dysfunction, 1999;68:183–192.
and hyperkalemia in a 78-year-old woman. She began the 9. Pathak S, Multani AS, Banerji P, Banerji P. Ruta 6 selec-
decoction 1 day before development of dyspnea and 3 tively induces cell death in brain cancer cells but prolifera-
days before admission to an emergency department. A tion in normal peripheral blood lymphocytes: A novel
treatment for human brain cancer. Int J Oncol 2003;23:
causal connection between rue and her symptoms was
not established because of the presence of pre-existing
10. Banerji P, Banerji P. Intracranial cysticercosis: an effective
disease and the lack of serum drug concentrations of her
treatment with alternative medicines. In Vivo 2001;15:
prescribed medications (i.e., bisoprolol, diltiazem).
11. Touati D, Atta-ur-Rahman, Ulubelen A. Alkaloids from
DIAGNOSTIC TESTING Ruta montana. Phytochemistry 2000;53:277–279.
12. Ulubelen A, Guner H, Cetindag M. Alkaloids and couma-
Methods for analyzing the constituents of extracts from
rins from the roots of Ruta chalepensis var. latifolia. Planta
Ruta species include GC with nitrogen-phosphorus or Med 1988;54:551–552.
flame ionization detection,1,2 gas/liquid chromatogra-
13. Ivanova A, Kostova I, Rodriguez Navas H, Villegas J.
phy,25 and GC/MS.13 Volatile components of some Rutaceae species. Z Natur-
forsch 2004;59:169–173.
TREATMENT 14. Hale AL, Meepagala KM, Oliva A, Aliotta G, Duke SO.
Phytotoxins from the leaves of Ruta graveolens. J Agric
Treatment is supportive. Therapy for skin lesions Food Chem 2004;52:3345–3349.
includes antihistamines, soothing baths to reduce pruri- 15. Ekiert H, Czygan F-C. Accumulation of biologically active
tus, and topical corticosteroid creams. Oral steroids furanocoumarins in agitated cultures of Ruta graveolens
may be necessary for more severe cases of rue-induced L. and Ruta graveolens ssp. divaricata (Tenore) Gams.
phytophotodermatitis. The use of soap and water, sun Pharmazie 2005;60:623–626.
screens, and avoidance of sun exposure for 48 hours 16. Mancebo F, Hilje L, Mora GA, Castro VH, Salazar R.
reduces the severity of phytophotodermatitis if initiated Biological activity of Ruta chalepensis (Rutaceae) and
before the appearance of skin lesions. Sechium pittieri (Cucurbitaceae) extracts on Hypsipyla
grandella (Lepidoptera: Pyralidae) larvae. Rev Biol Trop
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