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Rue

Scientific Name(s): Ruta bracteosa L., Ruta chalepensis L., Ruta graveolens L., Ruta montana L.
Common Name(s): Bitter-wort, Common rue, Fringed rue, Garden rue, German rue, Herb of Grace, Meadow rue, Rue, Sadab

Medically reviewed by Drugs.com. Last updated on Aug 1, 2021.

Clinical Overview

Use

Rue has traditionally been used to treat certain neuromuscular conditions and to stimulate the onset of menstruation. Rue has an antispasmodic effect at relatively low doses and should be taken with caution. Because of rue's potential for severe adverse effects, clinical trials are limited; therefore, use cannot be recommended for any indication.

Dosing

There is no clinical evidence to support dosing recommendations for rue. In larger doses, rue is an emmenagogue and an abortifacient, and is considered unsafe.

Contraindications

Use is contraindicated during pregnancy.

Pregnancy/Lactation

Avoid use. Rue is not recommended during lactation and is contraindicated in pregnancy. Adverse effects, including emmenagogue and abortifacient effects, have been documented.

Interactions

None well documented.

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. The literature describes potential abortifacient effects, indicating a contraindication of use during pregnancy. Toxic hepatitis due to a "Ruta herbal medicine" has been reported.

Toxicology

Rue should only be taken with extreme caution. Large doses can cause violent gastric pain, vomiting, and systemic complications, including death. A case report describes multiorgan toxicity in a 78-year-old woman consuming R. graveolens for cardiovascular protection. After 3 days of use, the patient entered the emergency department with bradycardia, coagulopathy, and acute renal failure with hyperkalemia requiring hemodialysis.

Scientific Family

  • Rutaceae (rue)

Botany

Rue is native to Europe but is cultivated worldwide. An herbaceous evergreen half-shrub that grows to 20 to 60 cm in height, it is often found growing along roadsides and in waste areas. The leaves have a feathery appearance and are green or blue-green, and the flowers are yellow with petals that are 1 cm in diameter.(Coimbra 2020, Furniss 2007) The plant is strongly scented, ornamental, and medicinal.(Chevallier 1996, Coimbra 2020) R. graveolens has a strong aroma and very intense bitter taste.(Mancuso 2015)

History

Roman naturalist Pliny the Elder (23 to 79 AD) mentions 84 remedies containing rue.(Duke 1989) Traditional medicinal uses include hypoglycemic, antirheumatic, intestinal, hepatic, antihelmintic, antiepileptic, and antipyretic.(Khadhri 2017) The leaves, extracts, and other parts of rue have been used for hundreds of years for their insect repellent properties. In folk medicine, rue has been used as an antispasmodic, sedative, and stimulant for the onset of menses.(Chevallier 1996, Coimbra 2020, Conway 1979, Duke 1989) Rue has also been used to treat ailments such as earache, eye strain, multiple sclerosis, Bell palsy, and heart conditions.(Chevallier 1996, Duke 1989) In South Africa, it has been used to treat hysteria.(Stafford 2008) In some cultures, rue extracts have been used for abortifacient purposes.(Coimbra 2020, Conway 1979)

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.(Pollio 2008) Rue was also used in ancient Greece and Egypt to strengthen eyesight.(Chevallier 1996)

Chemistry

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.(Tyler 1987, Wolters 1981)

The acridone alkaloids (rutacridone epoxide, hydroxyrutacridone epoxide) are found in greatest concentration in the roots.(Verzár-Petri 1976) Other alkaloids include graveoline, graveolinine, kokusaginine, rutacridone, and skimmianine. The flavonoid rutin is also present in the plant.(Chevallier 1996, Duke 1989)

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.(Spoerke 1990)

The plant and its oil are rich in coumarin derivatives, which appear to contribute to the pharmacologic activity of rue. These furocoumarins include bergapten, psoralen, xanthoxanthin, xanthotoxin, isopimpinellin, and rutamarin.(Chevallier 1996, Duke 1989, Haesen 1971) Isolation of such furocoumarins has been performed using an improved extraction technique.(Zobel 1988) Other reports have described isolation of the alkaloid isogravacridonchlorine from rue roots,(Paulini 1991) identification of dihydropyrano- and dihydrofuro-(Conway 1979, Duke 1989, Minker 1980, Tyler 1987, Wolters 1981) quinolinium alkaloids,(Montagu 1989) and purification of acridone synthase from rue cell cultures.(Baumert 1994)

Uses and Pharmacology

Anti-inflammatory effects

Animal and in vitro data

In a murine model, R. graveolens exerted anti-inflammatory activity and reduced edema in affected arthritic paws. An alkaloid fraction of R. graveolens given at a dose of 10 mg/kg demonstrated a larger anti-inflammatory effect compared with a polyphenolic fraction of R. graveolens and diclofenac.(Ratheesh 2010)

R. graveolens was found to suppress the production of nitric oxide from lipopolysaccharide in murine macrophage cells, suggesting potential anti-inflammatory activity.(Raghav 2006)

An experiment in Helicobacter pylori–infected gastric epithelial cells evaluated 24 medicinal plants indigenous to Pakistan for their effects on secretion of interleukin 8 (IL-8) and generation of reactive oxygen species in order to assess their anti-inflammatory and cytoprotective effects. Although no direct cytotoxic effects on the gastric cells or bactericidal effects on H. pylori were found, rue leaf extract 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.(Zaidi 2012)

Antimicrobial effects

In vitro data

More than 15 compounds in rue have been identified as having in vitro antibacterial and antifungal activity. 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.(Wolters 1981)

One report suggests that extracts of R. graveolens demonstrate inhibitory effects against gram-positive organisms such as Staphylococcus aureus, Streptococcus pyogenes, Listeria monocytogenes, and Bacillus subtilis.(Ivanova 2005) Other researchers have found that a number of components of rue interfere directly with DNA replication, thereby preventing the propagation of some viruses.(Novák 1967) Although it did not exert bactericidal effects against H. pylori, leaf extract of rue was observed to exhibit anti-inflammatory effects in H. pylori–infected gastric cells.(Zaidi 2012) An in vitro study suggests that a methanolic extract of R. graveolens exerted antibacterial activity against Streptococcus mutans and Streptococcus sobrinus, bacteria that cause dental caries.(Salman 2018)

Antioxidant effects

Animal and in vitro data

In an in vitro study, extracts of R. chalepensis and R. montana exerted acetylcholinesterase inhibition and antioxidant activity. Acetylcholinesterase activity was not reduced by artificial gastric or pancreatic juices.(Khadhri 2017) The effects of a hydroalcoholic extract of R. graveolens and rutin on memory were assessed in a rat model. Both the extract and rutin improved spatial memory and exerted antioxidant effects.(Asgharian 2020)

Clinical data

In a study of 56 patients with colorectal cancer (34 with early stage and 22 with advanced stage), an ethanolic extract of R. chalepensis protected erythrocytes from oxidative stress caused by free radicals. Specifically, this effect was noted in patients with early-stage colorectal cancer but was not observed for advanced disease.(Acquaviva 2011)

Antispasmodic effects

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 coumarins, in particular rutamarin. While the pharmacologic half-life of arborinine is similar to 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.(Minker 1980)

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.(Minker 1980)

Cancer/Cytotoxicity

Animal data

In a murine model of peritoneal sarcoma, R. graveolens was found to boost antitumor immunogenicity, promote apoptosis, and diminish tumor cell division.(Law 2018)

Cardiovascular effects

Animal and in vitro data

R. graveolens extract has been studied as a potential potassium channel blocker of ionic currents in myelinated nerve cells.(Bethge 1991) In isolated rat hearts treated with R. graveolens extract, concentration-dependent increases were seen in atrioventricular conduction time, Wenckebach cycle length, and effective and functional refractory periods.(Khori 2008) In rats given a methanolic extract of R. graveolens 20 mg/kg/day for 90 days, decreases in total cholesterol, low-density lipoprotein (LDL), and atherogenic indices were observed. Additionally, high-density lipoprotein (HDL) levels increased in rats given R. graveolens. Oxidative stress and inflammation measures were also reduced.(Ratheesh 2011) A similar model in hypercholesterolemic rabbits conducted by the same lead investigator found that an alkaloid fraction of R. graveolens dosed at 10 mg/kg/day for 90 days was associated with a reduction in total cholesterol and LDL cholesterol levels and an increase in HDL levels. Additionally, oxidative stress and inflammation were attenuated with R. graveolens.(Ratheesh 2013)

Clinical data

One clinical trial in patients with evidence of atherosclerosis (N=40) evaluated use of 6 g/day of dried, powdered R. graveolens for 90 days, with significant results observed for right Ankle Brachial Index (ABI) (P<0.002), left ABI (P<0.01), and LDL level (P<0.05) and no significant differences observed for Arterial Stiffness Index or other objective parameters (eg, total cholesterol, triglycerides, HDL).(Naaz 2019)

Neurodegenerative disease

R. graveolens has demonstrated monoamine oxidase-B inhibitory activity.(Colucci-D'Amato 2020)

Dosing

There is no clinical evidence to support dosing recommendations for rue. In larger doses, rue is an emmenagogue and an abortifacient, and is considered unsafe.(Gruenwald 2000)

Pregnancy / Lactation

Avoid use. R. graveolens contains rutin, which has emmenagogue potential. Various species of rue can stimulate the basal fiber of the uterus. Rue is not recommended during lactation and is contraindicated in pregnancy, as it has the potential to stimulate uterine contractions and can cause abortion.(Bernstein 2020, Duke 2002, Miguel 2003)

Interactions

None well documented.

Adverse Reactions

Because the antispasmodic effect of rue occurs at relatively small doses, it should be taken with extreme caution. Safety of the plant during pregnancy has not been established; most of the literature describes potential abortifacient effects, indicating a contraindication of use during pregnancy.(Chevallier 1996, Duke 1989)

Psoralens from rue that have come into contact with skin and been exposed to ultraviolet A light are responsible for photodermatitis.(Eickhorst 2007) Several case reports of photodermatitis following R. graveolens have been reported.(Arias-Santiago 2009, Eickhorst 2007, Furniss 2007) 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. The patient 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.(Arias-Santiago 2009) Another case report describes a 2-year-old child with erythema and blistering of the lower half of the face and hands following exposure to rue while playing in the family garden.(Furniss 2007) A third case involved a 1% superficial partial thickness contact burn to the hand of a 50-year-old male with blistering that began 2 days after initial contact with the rue plant. By day 3, blistering became more pronounced and was deroofed with skin loss, pain increased, range of movement of his hand decreased, and hyperpigmentation was found adjacent to the wound. The wound healed with 10 days after treatment with silver sulfadiazine.(Radotra 2018)

In albino male rats, R. graveolens L. 500 mg/kg for 60 days caused decreases in reproductive organ weight, sperm motility, spermatogenesis, number of spermatocytes and spermatids, and the number of impregnated female rats.(Khouri 2005) Another murine study demonstrated a temporary reduction in sperm motility 1 hour after receiving a dose of 5 g/kg of an aqueous extract of R. graveolens. Sperm motility improved after this time period and was normalized by 6 hours after the dose.(Halvaei 2012) 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.(Harat 2008)

Toxic hepatitis due to a "Ruta herbal medicine" has been reported.(Rabaev 2011)

The volatile oil has an irritant quality and may result in kidney damage and hepatic degeneration if ingested.(Spoerke 1990)

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.(Paulini 1987, Paulini 1989)

The dried leaves are likely less toxic than the fresh leaves because of the loss of volatile oil.(Heskel 1983, Ortiz-Frutos 1995) A tincture of R. graveolens exhibited marked photomutagenicity of varying degrees based on various alkaloid concentrations present in the compound.(Schimmer 1990)

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.(Leung 1980)

A case report describes multiorgan toxicity in a 78-year-old woman consuming R. graveolens for cardiovascular protection. After 3 days of use, the patient entered the emergency department with bradycardia, coagulopathy, and acute renal failure with hyperkalemia requiring hemodialysis.(Seak 2007)

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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