Scientific Name(s): Ruta bracteosa L., Ruta chalepensis L., Ruta graveolens L., Ruta montana L.
Common Name(s): Common rue, Fringed rue, Garden rue, German rue, Herb of Grace, Meadow rue, Rue
Rue is native to Europe but is now cultivated worldwide. It is often found growing along roadsides and in waste areas. An herbaceous evergreen half-shrub that grows to 61 cm in height, the leaves have a feathery appearance and are green or blue-green. Its flowers are yellow with petals that are 1 cm in diameter.1 The plant is ornamental and medicinal.2
The leaves, extracts, and other parts of rue have been used for hundreds of years as an 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.3
In Mediterranean traditional medicine, Ruta has been used to treat pulmonary conditions, such as tuberculosis, and to reduce swelling of the spleen, as well as externally to treat wounds.4
In New Mexico, 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.
Rue has been studied extensively.6 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.7, 8
The acridone alkaloids (rutacridone epoxide, hydroxyrutacridone epoxide) are found in greatest concentration in the roots.9 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.2, 5
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.10
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.2, 5, 11 Isolation of such furocoumarins has been performed using an improved extraction technique.12 Other reports have described isolation of the alkaloid isogravacridonchlorine from rue roots13; identification of dihydropyrano- and dihydrofuro-3, 5, 6, 7, 8 quinolinium alkaloids14; and purification of acridone synthase from rue cell cultures.15
Uses and Pharmacology
Cardiovascular and antioxidant effects
R. graveolens extract has been studied as a potential potassium channel blocker of ionic currents in myelinated nerve cells.16
In isolated rat hearts treated with R. graveolens extract, a concentration-dependent effect increase was seen in atviroventricular-conduction time, Wenckebach cycle length, and effective and functional refractory periods.17 Rats given a methanolic extract of R. graveolens 20 mg/kg/day for 90 days were found to have lower total cholesterol, low-density lipoprotein levels, and atherogenic indices. Additionally, high-density lipoprotein levels increased in rats given R. graveolens. Oxidative stress and inflammation measures were also reduced.18
In a study of 56 patients with colorectal cancer (34 with early stage and 22 with advanced stage), R. chalepensis was found to protect erythrocytes from oxidative stress caused by radicals. Specifically, this effect was noted in patients with early-stage colorectal cancer and was not observed with advanced disease.19
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.2, 5 In South Africa, it has been used to treat hysteria.20
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 is about the same as that of papaverine, the half-life of rutamarin is approximately 20 times longer. These spasmolytic effects have also been observed in isolated GI smooth muscle.6
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.
The abortifacient effects of rue teas and oil are well documented. The abortifacient effect may be due to an anti-implantation action2 or to a generalized state of systemic toxicity resulting in fetal death.10
In a murine model, R. graveolens was found to exert anti-inflammatory activity as well as reduce edema in affected arthritic paws. Particularly, it was the alkaloid fraction of R. graveolens given at a dose of 10 mg/kg that demonstrated a larger anti-inflammatory effect as compared with the polyphenolic fraction and diclofenac.23
R. graveolens was found to suppress the production of nitric oxide from lipopolysaccharide in murine macrophage cells, suggesting potential anti-inflammatory activity.24
More than 15 compounds in rue have been identified as having in vitro antibacterial and antifungal activity.8 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. One report suggests that extracts of R. graveolens demonstrated inhibitory effects against gram positive organisms such as Staphylococcus aureus, Streptococcus pyogenes, Listeria monocytogenes, and Bacillus subtilis.25 Other researchers have found that a number of components of rue interfere directly with DNA replication, thereby preventing the propagation of some viruses.26 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.2, 5 Experimentation in H. pylori-infected gastric epithelial cells with 24 medicinal plants indigenous to Pakistan was conducted to evaluate their effect on secretion of interleukin (IL)-8 and generation of reactive oxygen species (ROS) in order to assess anti-inflammatory and cytoprotective effects. Although no significant direct cytotoxic effects on the gastric cells or bactericidal effects on H. pylori were found, leaf extract of rue was observed to have moderate and strong inhibitory activity on IL-8 at 50 and 100 mcg/mL, respectively, in H. pylori-infected gastric cells.42
There is no 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.27
Pregnancy / Lactation
None well documented.
Because the antispasmodic effect of this plant occurs at relatively small doses, rue should only be taken with extreme caution. 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.2, 5
Psoralens from rue that have come in contact with skin and exposed to ultraviolet A light are responsible for photodermatitis.30 Several case reports of photodermatitis following R. graveolens have been reported.1, 30, 31 One case report describes the presence of blisters and erythema in a 48-year-old woman who used an infusion of R. graveolens for the management of fibromyalgia. She had been exposed to the sun and subsequently developed vesicles and erythema in the center and lateral areas of the back. She was treated with corticosteroids, antibiotics and analgesics, and the lesions disappeared within 2 weeks.31 Another case report describes a 2-year-old child with erythema and blistering of the lower half of his face and hands following exposure to rue while playing in his family's garden.1
In albino male rats, R. graveolens L. 500 mg/kg for 60 days caused a decrease in the weight of reproductive organs, sperm motility, spermatogenesis, number of spermatocytes and spermatids, and the number of impregnated female rats.32 In a study of human sperm, a dose-dependent effect was noted on the immobilization of sperm, with the minimum effective dose determined to be 100 mg/mL.33
Toxic hepatitis due to Ruta has been reported.34
The volatile oil has an irritant quality; it may result in kidney damage and hepatic degeneration if ingested.10
The toxicity of the dried leaves is most likely less than that of the fresh leaves because of the loss of volatile oil.37, 38 A tincture of R. graveolens exhibited marked photomutagenicity of varying degrees based on various alkaloid concentrations present in the compound.39
Large doses (more than 100 mL of the oil or approximately 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 was 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.40
A case report describes multiorgan toxicity in a 78-year-old woman ingesting R. graveolens for cardiovascular protection. After 3 days of use, the patient entered the emergency department with bradycardia, acute renal failure with hyperkalemia necessitating hemodialysis, and coagulopathy.41
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