Natural Products (Professional)

Rue

Scientific Name(s): Ruta graveolens L., R. montana L. and R. bracteosa L. Family: Rutaceae

Common Name(s): Rue , common rue , garden rue , German rue . Not to be confused with meadow rue ( Thalictrum spp.)

Clinical Overview

Uses of Rue

Rue extract is potentially useful as a potassium channel blocker. It has been used to treat many neuromuscular problems and to stimulate onset of menstruation. Because rue has an antispasmodic effect at relatively low doses, it should be taken with caution.

Rue Dosing

There is no recent clinical evidence to support dosing recommendations for rue. Traditional use calls for 0.5 to 1 g of the herb daily or 65 mg of the essential oil. In larger doses, rue is an emmenagogue, an aphrodisiac, and an abortifacient, and should be considered dangerous.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Documented adverse effects, including emmenagogue and abortifacient effects. Avoid use.

Rue Interactions

None well documented.

Rue Adverse Reactions

Rue extracts are mutagenic and furocoumarins have been associated with photosensitization. If ingested, rue oil may result in kidney damage and hepatic degeneration. Large doses can cause violent gastric pain, vomiting, and systemic complications, including death. Because of possible abortifacient effects, the plant should never be ingested by women of childbearing potential.

Toxicology

Rue should only be taken with caution, if at all.

Botany

Rue is native to Europe but is now cultivated worldwide. It is often found growing along roadsides and in waste areas. It is an herbaceous evergreen half-shrub that grows to 1 m in height. The leaves have 3 fleshy lobes and are teardrop-shaped. It blooms greenish-yellow flowers from June to August. The flowers have a characteristically disagreeable odor. The aerial parts, which are gathered in the summer, are used. The plant is both ornamental and medicinal. 1

History

The leaves, extracts, and other parts of rue have been used for hundreds of years as insect repellent. In folk medicine, rue has been used as an antispasmodic, sedative, and stimulant for the onset of menses. In some cultures, rue extracts have been used as abortifacients. 2

In the New Mexico region, rue has been used as a tisane (tea) for ailments such as stiff neck, dizziness, headache, tightness in the stomach, and inner ear problems. The oil has a strong bitter taste and has been used for the treatment of intestinal worms.

Roman naturalist Pliny the Elder (23 to 79 AD) mentions 84 remedies containing rue. 3 Aside from its use as an abortifacient, rue was also used in ancient Greece and Egypt to strengthen eyesight. 1

Chemistry

Rue has been studied extensively. 4 Common rue contains a mixture of furoquinoline alkaloids in a concentration of approximately 1.5%, the most important of which appear to be arborine, arborinine, and gamma-fagarine. 5 , 6

The acridone alkaloids (rutacridone epoxide, hydroxyrutacridone epoxide) are found in greatest concentration in the roots. 7 Other alkaloids include graveoline, graveolinine, kokusaginine, rutacridone, and skimmianine. The flavonoid rutin is also present in the plant and is said to support and strengthen blood vessels, which reduces pressure. 1 , 3

A volatile oil is present in a concentration of approximately 0.1%. The oil is 90% methyl-nonylketone with the balance composed of related ketones, esters, and phenols. 8

The plant and its oil are rich in coumarin derivatives, which appear to contribute to the pharmacologic activity of the plant. These furocoumarins include bergapten, psoralen, xanthoxanthin, xanthotoxin, isopimpinellin, and rutamarin. 1 , 3 , 9 Isolation of such furocoumarins has been performed using an improved extraction technique. 10 A new coumarin, “exo-dehydrochalepin” has been synthesized from rutamarin. 11 Other reports have described isolation of alkaloid isogravacridonchlorine from rue roots; 12 identification of dihydropyrano- and dihydrofuro- 2 , 3 , 4 , 5 , 6 quinolinium alkaloids; 13 and purification of acridone synthase from rue cell cultures. 14

Rue Uses and Pharmacology

The rue plant and its extracts, in particular the tea and oil, have been reported to have antispasmodic effects on smooth muscles. This pharmacologic action has been attributed to the alkaloids arborine and arborinine and to the coumarins, in particular rutamarin. While the pharmacologic half-life of arborinine was about the same as that of papaverine, the half-life of rutamarin was approximately 20 times longer. These spasmolytic effects were also observed in isolated gastrointestinal smooth muscle. 4

R. graveolens extract has been studied as a potential potassium channel blocker of ionic currents in myelinated nerve cells. 15

The abortifacient effects of rue teas and oil are well documented. The abortifacient effect may be due to an anti-implantation action 2 or to a generalized state of systemic toxicity resulting in fetal death. 8

More than 15 compounds in rue have been identified as having in vitro antibacterial and antifungal activity. 6 The acridone alkaloids are the most potent antimicrobial compounds; the coumarins inhibit growth only at high doses. The essential oil and flavonoids tested did not show activity. Other researchers have found that a number of components of rue interact directly with DNA replication, thereby preventing the propagation of some viruses. 16 The leaf of rue is said to alleviate cancer of the mouth, as well as tumors and warts. In Chinese medicine, rue is used as a vermifuge and for insect bites. 1 , 3

Animal data

One study found the spasmolytic effect of arborinine on pig coronary muscle to be as potent as that of papaverine, while rutamarin was 20-fold more potent than papaverine. The antispasmodic effects of these compounds were reversible.

Antifertility action of R. graveolens has been reported in rats. 17 , 18 In 1 report, chalepensin was found to be the active component, acting at early stages of pregnancy. 17

Clinical data

Rue has been used to treat many ailments, including epilepsy, eye strain, multiple sclerosis, Bell palsy, and heart conditions. It has also been used as a uterine stimulant to encourage onset of menstruation. 1 , 3

Dosage

There is no recent clinical evidence to support dosing recommendations for rue. Traditional use calls for 0.5 to 1 g of the herb daily or 65 mg of the essential oil. In larger doses, rue is an emmenagogue, aphrodisiac, and an abortifacient, and should be considered dangerous. 19

Pregnancy/Lactation

Documented adverse effects, including emmenagogue and abortifacient effects. 20 , 21 Avoid use.

Interactions

None well documented.

Adverse Reactions

Because the antispasmodic effect of this plant occurs at relatively small doses, rue should only be taken with caution, if at all. The safety of the plant in pregnant women has not been established, and most of the literature describing its potential abortifacient effects indicates that the plant should never be ingested by women of childbearing potential. 1 , 3

The furocoumarins have been associated with photosensitization, resulting in skin blistering following contact and exposure to sunlight. This occurs in people who collect fresh rue and has been reported in those who rubbed fresh rue on themselves as an insect repellent.

The volatile oil has an irritant quality; it may result in kidney damage and hepatic degeneration if ingested. 8

Toxicology

Extracts of rue have been found to be mutagenic in experimental mutagenicity screens, but the clinical importance of these findings has not been established. 22 , 23

The toxicity of the dried leaves is most likely less than that of the fresh leaves because of the loss of volatile oil. 24 , 25 A tincture of R. graveolens exhibited marked photomutagenicity of varying degrees based on various alkaloid concentrations present in the compound. 26

Large doses (more than 100 mL of the oil or about 120 g of the leaves in 1 dose) can cause violent gastric pain, vomiting, and systemic complications, including death. A single oral dose of 400 mg/kg given to guinea pigs has been reported to be fatal because of hemorrhages of the adrenal gland, liver, and kidney. However, a daily oral dose of 30 mg given to human subjects for 3 months did not result in abnormal hepatic function. 27

Bibliography

1. Chevallier A . The Encyclopedia of Medicinal Plants . New York, NY: DK Publishing; 1996:262-263.
2. Conway GA , Slocumb JC . Plants used as abortifacients and emmenagogues by Spanish New Mexicans . J Ethnopharmacol . 1979;1:241-261.
3. Duke J . CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 1989:417-418.
4. Minker E , Bartha C , Koltai M , Rozsa Z , Szendrei K , Reisch J . Effect of secondary substances isolated from the Ruta graveolens L. on the coronary smooth muscle . Acta Pharm Hung . 1980;50:7-11.
5. Tyler VE . The New Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies . Philadelphia, PA: GF Stickley Co; 1987.
6. Wolters B , Eilert U . Antimicrobial substances in callus cultures of Ruta graveolens . Planta Med . 1981;43:166-174.
7. Verzar-Petri VG , Csedo K , Mollmann K , Szendrei K , Reisch J . Fluorescence microscopic investigations on the localisation of acridone alkaloids in the organs of Ruta graveolens [in German]. Planta Med . 1976;29:370-375.
8. Spoerke DG . Herbal Medications . Santa Barbara, CA: Woodbridge Press; 1980.
9. Haesen JP , Vorde Sive Vording JG , Kho KF . Isolation and identification of xanthotoxin from the underground parts of Ruta graveolens . Planta Med . 1971;19:285-289.
10. Zobel AM , Brown SA . Determination of furanocoumarins on the leaf surface of Ruta graveolens with an improved extraction technique. J Nat Prod . 1988;51:941-946.
11. Reisch J , et al. Sci Pharm . 1988;56:171-174.
12. Paulini H , Popp R , Schimmer O , Ratka O , Roder E . Isogravacridonchlorine: a potent and direct acting frameshift mutagen from the roots of Ruta graveolens . Planta Med . 1991;57:59-61.
13. Montagu M , Petit-Paly G , Levillain P , et al. Synchronous fluorescence spectrometry and identification of dihydrofuro[2,3-b]quinolinium alkaloids biosynthesized by Ruta graveolens cultures in vitro. Pharmazie . 1989;44:342-344.
14. Baumert A , Maier W , Groger D , Deutzmann R . Purification and properties of acridone synthase from cell suspension cultures of Ruta graveolens L . Z Naturforsch [C] . 1994;49:26-32.
15. Bethge EW , Bohuslavizki KH , Hansel W , Kneip A , Koppenhofer E . Effects of some potassium channel blockers on the ionic currents in myelinated nerve . Gen Physiol Biophys . 1991;10:225-244.
16. Novak I , Buzas G , Minker E , Koltai M , Szendrei K . Isolation of some effective substance from the herb Ruta graveolens L. [ in Hungarian]. Acta Pharm Hung . 1967;37:130-141.
17. Kong YC , Lau CP , Wat KH , et al. Antifertility principle of Ruta graveolens . Planta Med . 1989;55:176-178.
18. Gandhi M , Lal R , Sankaranarayanan A , Sharma PL . Post-coital antifertility action of Ruta graveolens in female rats and hamsters . J Ethnopharmacol . 1991;34:49-59.
19. Gruenwald , et al, eds. PDR for Herbal Medicines . 2nd ed. Montvale, NJ: Medical Economics Company; 2000:649.
20. Brinker FJ . Herb Contraindications and Drug Interactions . 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998.
21. Ernst E . Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109:227-235.
22. Paulini H , Eilert U , Schimmer O . Mutagenic compounds in an extract from rutae herba ( Ruta graveolens L.). I. Mutagenicity is partially caused by furoquinoline alkaloids . Mutagenesis . 1987;2:271-273.
23. Paulini H , Schimmer O . Mutagenicity testing of rutacridone epoxide and rutacridone, alkaloids in Ruta graveolens L., using the Salmonella/microsome assay . Mutagenesis . 1989;4:45-50.
24. Heskel NS , Amon RB , Storrs FJ , White CR Jr . Phytophotodermatitis due to Ruta graveolens . Contact Dermatitis . 1983;9:278-280.
25. Ortiz-Frutos FJ , Sanchez B , Garcia B , Iglesias L , Sanchez-Mata D . Photocontact dermatitis from rue ( Ruta montana L.) . Contact Dermatitis . 1995;33:284.
26. Schimmer O , Kuhne I . Mutagenic compounds in an extract from Rutae Herba ( Ruta graveolens L.). II. UV-A mediated mutagenicity in the green alga Chlamydomonas reinhardtii by furoquinoline alkaloids and furocoumarins present in a commercial tincture from Rutae Herba . Mutat Res . 1990;243:57-62.
27. Leung AY. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics . New York, NY: Wiley; 1980.