Pennyroyal (Mentha pulegium L. / Hedeoma pulegioides)
1. Identity, Taxonomy, and Botanical Description
The common name pennyroyal refers principally to two distinct but botanically related plants that share similar chemistry and overlapping traditional uses. Two similar plants go by the name pennyroyal, one native to Europe (called European pennyroyal) and one native to North America (called American pennyroyal). Both are members of the mint family (Lamiaceae) and grow in temperate regions of Europe and the Americas.
- European pennyroyal: Mentha pulegium L. Commonly also called pennyrile, mosquito plant, and pudding grass, it is a species of flowering plant in the mint family, Lamiaceae, native to Europe, North Africa, and the Middle East. It is an annual to perennial plant with creeping or erect branched stems to about 40 cm in height.
- American pennyroyal: Hedeoma pulegioides (L.) Pers. Also known as pennyrile, American pennyroyal, or American false pennyroyal, it is native to eastern North America, from Nova Scotia and southern Ontario west to Minnesota and South Dakota, and south to northern Georgia and Arkansas. It is a low-growing, strongly aromatic herbaceous annual plant from 15 to 30 cm tall, with a slender erect much-branched, somewhat hairy and square stem.
These two herbs, though classified in different genera, have similar chemical constituents and medicinal properties. The common name pennyroyal is associated with Latin pulex (flea), alluding to the manner it was used to drive away fleas when smeared on the body.
M. pulegium leaves, when crushed, emit a very strong fragrance similar to spearmint. This perennial plant is characterized by its aromatic leaves and small violet flowers, contributing to its historical use in various cultures.
Common Synonyms and Folk Names
Folk names for pennyroyal include true pennyroyal, English pennyroyal, European pennyroyal, mock pennyroyal, pudding grass, pulegium, polei, poleo, yarpuz, tickweed, stinking balm, thick weed, mosquito plant, squaw mint, and squaw balm.
Common Preparations and Dosage Forms
Pennyroyal is available in several forms. The plant is a perennial herb historically used to make tea and tincture, and commercially processed pennyroyal capsules exist, as does pennyroyal essential oil extracted from compressed plants. The extraction of pennyroyal essential oil typically involves steam distillation. The flowering tops are used as medicine, but internal use of the volatile oil should be strictly avoided. Dried herb preparations are used primarily as infusions (teas), while the essential oil has been used externally as an insect repellent and, historically and dangerously, internally as an abortifacient.
2. Traditional and Historical Use
Ancient Greece and Rome
Documented use of pennyroyal dates back to ancient Greek, Roman, and Medieval cultures. Pennyroyal was commonly incorporated as a cooking herb by the Greeks and Romans. A large number of the recipes in the Roman cookbook of Apicius called for the use of pennyroyal, often along with herbs such as lovage, oregano, and coriander.
Records from Greek and Roman physicians and scholars contain information pertaining to pennyroyal's medicinal properties, as well as recipes used to prepare it. Pliny the Elder, in his encyclopedia Naturalis Historia (Natural History), described the plant as an emmenagogue and noted that it also expelled a dead fetus. Ancient Greeks and Romans valued its properties not just for culinary purposes but also for its application in treating health issues.
Since the time of the ancient Greeks, pennyroyal was considered a useful insect repellent, reflected in modern times by the common name fleabane. The Latin names of both plants also reflect this insect-repelling power — pulegoides and pulegium both derive from the Latin word for flea.
Medieval Europe
Although pennyroyal was commonly used for cooking in the Middle Ages, it gradually fell out of use as a culinary herb and is seldom used as such today. It continued, however, to be an important figure in medieval herbal medicine. Pliny gave a long list of disorders for which pennyroyal was a supposed remedy, especially recommending it for hanging in sleeping rooms, it being considered by physicians as more conducive to health even than roses.
Rennie's 1833 supplement to the pharmacopeias admitted its use as an "expectorant, diuretic, and emmenagogue" in doses of 10 grains to 1 scruple (0.6–1.3 g) of the powdered dried herb.
Native American Traditions
American pennyroyal (Hedeoma pulegioides) was used extensively by Native Americans to treat a variety of ailments from headache and stomach distress to itching, watery eyes, and fevers. For external use, the leaves were crushed and applied to the skin to repel mosquitoes and other insects. Long before colonial settlers arrived, various Eastern Woodland tribes — including the Iroquois and Ojibwe — harvested Hedeoma pulegioides for digestive upsets, menstrual cramps, and insect bites.
Folk Use as Emmenagogue and Abortifacient
Pennyroyal extracts were used as a traditional herb and folk remedy; a particular use was to stimulate menstruation and, in higher concentrations, to induce abortion. The dry parts of pennyroyal and its essential oil have been used in traditional medicine for liver and gallbladder ailments, digestive complaints, gout, amenorrhea, increased micturition, colds, and skin disorders, and as an abortifacient.
Various folk herb traditions have employed American or European pennyroyal to help relieve coughs, upset stomachs, and anxiety. Pennyroyal has a strong fragrance similar to spearmint and was used for centuries to flavor food, wine, and herbal teas.
Culinary Uses
Pennyroyal has historically also been used as a mint flavoring in herbal teas and foods. In Italy, the fresh leaves of this plant, known in Rome and the surrounding area as menta romana, are used in the capital's cuisine to flavour lamb and tripe.
3. Key Constituents and Chemical Composition
Volatile Oil / Essential Oil
The fresh herb yields about 1 per cent of a volatile oil — oil of Pulegium — a yellow or greenish-yellow liquid obtained by distillation, having a strong aromatic odour and taste. The composition of the essential oil varies considerably by geographic origin and chemotype.
In one studied sample, pulegone was the major compound, constituting 88.64% of the pennyroyal essential oil. European and American pennyroyal oil consist of 80–90% and 16–30% (R)-(+)-pulegone, respectively. Another Moroccan sample showed pulegone at 76.35%, carvone at 5.84%, dihydrocarvone at 5.09%, and octanol-3 at 2.25%.
GC-MS analysis of oils from two Algerian regions revealed distinct chemotypes: one presented a pulegone-dominant profile (61%), whereas the other presented (+)-limonene/piperitone/piperitenone chemotypes of 41.99%, 23.08%, and 12.06%, respectively. Menthone, menthofuran, limonene, piperitone, and other monoterpenes may also appear depending on geography, harvest conditions, and extraction method. This variability means pennyroyal is not chemically identical from one batch to the next, and some chemotypes are more safety-problematic than others.
Principal Constituent: Pulegone
The major constituents of pennyroyal essential oils are pulegone, menthone, isomenthone, piperitone, menthol, neo-menthol, and 3-octanol. Among these, pulegone is the dominant and toxicologically most significant compound. The entire plant contains a variety of compounds including pulegone, isomenthone, carvone, menthofuran, menthol, 1,8-cineole, piperitone, piperitenone, neomenthol, α-humulene, and 3-octanol.
Polyphenols and Flavonoids
HPLC analysis has detected multiple flavonoids in M. pulegium, including chrysoeriol, kaempferol, 7-OH flavone, catechin, hesperidin, and luteolin. Plants of Egyptian origin have been found to contain acacetin, apigenin, and luteolin derivatives; those of Greek origin yielded caffeic acid, vanillic acid, ferulic acid, apigenin, luteolin, naringenin, and catechin; and Algerian-origin samples contained 4-hydroxy benzoic, caffeic, p-coumaric, chlorogenic, and rosmarinic acids, along with luteolin, diosmin, and kaempferol.
4. Mechanisms of Action
Hepatotoxic Mechanism of Pulegone
The toxic principal in pennyroyal oil appears to be pulegone, which is converted by the cytochrome P450 system (CYP1A2 and CYP2E1) to other hepatotoxins, primarily menthofuran. Pulegone was found to be metabolized to menthofuran by expressed human liver CYPs, primarily by CYP2E1, and to a lesser extent by CYP1A2 and CYP2C19. Menthofuran was metabolized to the greatest extent by CYP2E1.
The menthofuran is further oxidized to an epoxide, which is likely the ultimate toxic biological reactive intermediate that causes liver damage. Oxidative metabolites of pulegone (e.g., menthofuran) bind to cellular proteins and deplete hepatic glutathione, leading to liver injury.
Pulegone and its products deplete glutathione levels, and attempts at treating pennyroyal toxicity with N-acetylcysteine infusions are appropriate. The carbonyl center of the pulegone structure acts as a strong electrophile, causing active sites on enzymes to bind with pulegone instead of the target protein. The exocyclic double bond found in pulegone is vital to the activation and binding mechanism of the molecule and causes it to be an effective hepatotoxin.
Anti-inflammatory Mechanism
Research on M. pulegium extract in human peripheral blood mononuclear cells (PBMCs) demonstrated marked inhibition of pro-inflammatory mediators' expression and release, with the extract acting at the level of transcription mainly by preventing TLR-4 and NF-κB expression. Separately, pulegone has been shown to reduce LPS-induced inflammation by reducing the effects of NF-κB, suggesting it could be used to treat and prevent a variety of inflammatory illnesses.
Mechanism of Abortifacient Action
Pennyroyal's abortifacient properties are thought to be due to irritation of the uterus, causing contractions, but lethal doses are necessary for this to occur and the effect is inconsistent. Notably, research reviewed in pharmacological literature indicates that as early as 1913 it was found that pennyroyal essential oil has no specific or direct stimulating action on uterine muscle. The abortifacient action was concluded to be due to general poisoning or gastrointestinal irritation, making its use not only uncertain, but also extremely dangerous.
A 2022 animal study in pregnant rats (PMC9147109) found that administration of M. pulegium extract for three days starting from day 15 of gestation affected fetal development by disrupting the uterine and placental tissues, or even caused pregnancy termination. These effects entailed biochemical changes including decreased progesterone and increased estradiol serum levels, modulation of placental gene expression, and inflammatory responses (TNF-α, IL-1β).
Mechanism of Insecticidal Activity
Pulegone was shown to have antihistaminic activity on the guinea pig ileum, and pulegone demonstrated insecticidal activity based on lethality to Drosophila melanogaster.
5. Scientific Evidence by Area of Use
5.1 Antimicrobial Activity
Previous reports have shown that M. pulegium essential oil exhibits antibacterial activity against several bacterial strains. A 2021 study published in Antibiotics (PMC8532685) evaluated the antimicrobial and anti-quorum sensing activity of pennyroyal essential oil, with a particular focus on antibacterial activity against Acinetobacter baumannii, studying chemical composition by GC-MS/GC-FID. The results showed notable action against Acinetobacter baumannii, along with the capacity of the essential oil to inhibit quorum sensing mechanisms, suggesting potential use for developing surface disinfectants for hospitals. Evidence for antimicrobial activity is currently limited to laboratory (in vitro) studies; no human clinical trials have been conducted. Evidence strength: preliminary, in vitro only.
5.2 Antioxidant Activity
Multiple laboratory studies have evaluated the antioxidant properties of M. pulegium. One study reported antioxidant activity was detected with an IC50 of 18 µg/mL by DPPH assay. However, another recent study found the antioxidant potential of M. pulegium essential oils from both tested sites was assessed and found to be weak. Results across studies are inconsistent. Evidence strength: preliminary, mixed, in vitro only; no human clinical data.
5.3 Anti-inflammatory Activity
A study published in PMC (PMC10792569) evaluated anti-inflammatory effects of M. pulegium extract on human peripheral blood mononuclear cells (PBMCs). The hydro-ethanolic extract of M. pulegium was obtained and optimal non-cytotoxic concentrations were determined by MTT assay. Three concentrations (10, 30, and 90 µg/mL) were used to pre-treat LPS-stimulated and non-stimulated PBMCs of 10 healthy individuals. The study measured TNF-α, IL-1β, IL-6, TLR-4, NF-κB p65, AP-1, iNOS, COX-2 gene expressions, and related protein levels. The authors reported the first evidence that M. pulegium decreases the expression and biosynthesis of pro-inflammatory mediators in human LPS-stimulated PBMCs, and called for further studies to develop anti-inflammatory agents. More confirmatory studies are recommended to verify these results. Evidence strength: early-phase, single cell-culture study using human cells; no controlled clinical trials in humans.
5.4 Insect-Repellent Activity
Insecticidal activity of M. pulegium essential oil has been evaluated against stored-product pests using contact and inhalation tests. Pennyroyal oil has historically been used and studied as a flea and insect repellent. At least one study has shown pennyroyal oil to have potent acaricidal activity against house dust mites. Pulegone demonstrated insecticidal activity based on lethality to Drosophila melanogaster, as did mint oil extracted from European pennyroyal (M. pulegium). Evidence strength: mostly laboratory and animal studies; limited controlled human studies specifically on pennyroyal as an insect repellent.
5.5 Emmenagogue / Menstrual Effects
Pennyroyal has been used traditionally to stimulate menstruation and, in higher concentrations, to induce abortion. No controlled clinical trials in humans have evaluated pennyroyal specifically for the management of menstrual irregularity or dysmenorrhea. Evidence strength: traditional use only; no clinical trial evidence.
5.6 Digestive and Carminative Effects
Various research has revealed that M. pulegium extracts are frequently used as an anti-inflammatory, antispasmodic, carminative, antitussive, diaphoretic, antiemetic, analgesic, and stimulant, in the forms of powders, infusions, and decoctions. Pennyroyal's mint properties, attributable to the menthol component, theoretically may act in dilating respiratory passages in bronchitis or asthma when consumed as a tea. These remain theoretical or traditional claims; no human clinical trials have established efficacy.
5.7 Abortifacient Use
The use of pennyroyal oil as an abortifacient is one of the best-documented traditional applications, though modern clinical evidence confirms it is not a reliable abortifacient and carries extreme toxicity risk. Pennyroyal's abortifacient properties are thought to be due to irritation of the uterus causing contractions, but lethal doses are necessary for this to occur and the effect is inconsistent. The 2022 animal study (PMC9147109) in pregnant rats confirmed abortifacient capacity, but only in an animal model and at doses associated with significant toxicity. Evidence strength: animal and case-report data; no human clinical trials; the toxic dose required approaches or overlaps with lethal dose.
6. Body Systems and Health Areas Associated with Pennyroyal
- Hepatic (Liver) System: Primary target organ of toxicity. Pulegone and menthofuran are known direct hepatotoxins, causing centrilobular hepatic necrosis.
- Reproductive System: Historically used as an emmenagogue and abortifacient; associated with uterotonic activity, though the mechanism is general toxicity rather than specific uterine stimulation.
- Renal (Kidney) System: Acute renal failure has been documented in cases of pennyroyal oil ingestion.
- Central Nervous System: Studies in both animals and humans show that pulegone is directly toxic to the nervous system. Seizures, cerebral edema, and encephalopathy have been reported.
- Gastrointestinal System: Traditional use as a carminative, digestive, and antispasmodic; GI irritation is also a common feature of toxicity.
- Immune / Inflammatory System: In vitro evidence for inhibition of inflammatory pathways via TLR-4 and NF-κB suppression.
- Integumentary (Skin) System: External application as an insect repellent; a contact dermatitis case from M. pulegium has been reported in the medical literature (Contact Dermatitis 2005;53:355).
7. Dosage Forms and Dosages Reported in Sources
Rennie's 1833 pharmacopeia supplement admitted pennyroyal's use as an expectorant, diuretic, and emmenagogue in doses of 10 grains to 1 scruple (0.6–1.3 g) of the powdered dried herb.
In the laboratory study on anti-inflammatory effects in human PBMCs, three concentrations of M. pulegium hydro-ethanolic extract — 10, 30, and 90 µg/mL — were used to pre-treat PBMCs from 10 healthy individuals.
In the animal abortifacient study (PMC9147109), administration of MP extract and fractions was conducted for three days starting from day 15 of gestation. Specific doses by weight are reported in the primary publication.
A review of 18 previous case reports of pennyroyal ingestion documented moderate to severe toxicity in patients who had been exposed to at least 10 mL of pennyroyal oil. This represents a clinically observed toxic threshold, not a therapeutic dose recommendation.
Administration of N-acetylcysteine is recommended in all cases of ingestion of more than 10 mL of pennyroyal oil.
Regarding regulatory limits: The EMA derived an acceptable exposure limit of 0.75 mg/kg/day for pulegone, based on a NOAEL of 37.5 mg/kg/day from a 90-day subchronic study.
8. Safety Considerations and Drug Interactions
8.1 Acute Toxicity and Clinical Case Reports
When taken by mouth, pennyroyal oil is highly toxic and has been linked to several instances of toxic liver injury and death. At least 24 cases of pennyroyal toxicity have been documented, including liver and kidney failure, low blood sugar, blood clotting problems, acidic blood pH, GI hemorrhage, lung congestion, mental status changes, brain swelling, seizures, and death.
Two cases of pennyroyal oil ingestion for the purpose of abortion have been reported, one of which resulted in shock, disseminated intravascular coagulation (DIC), massive hepatic necrosis, and death. A clinical case series reported four cases of pennyroyal ingestion; one patient died, one received N-acetylcysteine, and two ingested minimally toxic amounts and were not treated with N-acetylcysteine.
There have been many reported cases of pennyroyal oil toxicity, usually arising within a few hours of ingestion. Cardiovascular collapse with disseminated intravascular coagulation is the usual presentation, but some patients develop acute liver injury with marked elevations in serum aminotransferase levels and early signs of liver failure. The clinical pattern of liver injury is acute hepatic necrosis that, if severe, can lead to acute liver failure and death. Immunoallergic features are uncommon. Liver biopsy shows marked centrilobular necrosis, which can resemble shock or acute acetaminophen overdose.
8.2 Infant Toxicity
Two cases of multiorgan failure have been reported in infants who were given pennyroyal herbal tea as home remedies. One infant developed fulminant liver failure with cerebral edema and necrosis; the other infant developed hepatic dysfunction and a severe epileptic encephalopathy. Consumption of pennyroyal tea can be fatal to infants and children.
8.3 Tea vs. Concentrated Oil
Pennyroyal tea and leaf extracts have been used without serious side effects; however, pennyroyal oil is highly toxic. This critical distinction between the dilute herb preparation and the concentrated volatile oil is consistently highlighted in the medical literature.
8.4 Carcinogenicity (Animal Data)
The NTP concluded that pulegone has clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of urinary bladder neoplasms, and increased incidences of hepatocellular neoplasms in male and female B6C3F1 mice. The International Agency for Research on Cancer (IARC) has classified pulegone as "Possibly carcinogenic to humans" (Group 2B), based on limited evidence for carcinogenicity in humans and less than sufficient evidence for carcinogenicity in experimental animals. There is clear evidence of carcinogenic activity in male and female B6C3F1 mice based on hepatocellular neoplasms, at doses two orders of magnitude greater than concentrations seen in herbal remedies.
8.5 Genotoxicity
Pulegone is genotoxic but not mutagenic, teratogenic, or a reproductive toxicant under the conditions studied. Pulegone, but not pennyroyal oil as a whole, was weakly mutagenic in Drosophila melanogaster in the wing spot test.
8.6 Drug Interactions
A case report of acute liver failure was possibly caused by drug interactions with pennyroyal tea, which makes use of CYP1A2, CYP2E1, and CYP2C19 as substrates. CYP2E1 in particular has been determined to be the major metabolizing enzyme for pulegone. This means pennyroyal has the potential to interact with any pharmaceutical drug that is metabolized by these same cytochrome P450 enzymes, including altering drug levels or additive liver injury.
Monomeric flavonoids in pennyroyal may complex with iron in the intestinal lumen and reduce iron bioavailability by 50% or more. This constitutes a clinically relevant interaction with iron supplements.
8.7 Pregnancy and Reproductive Risk
The volatile oil of pennyroyal is a folk medicine used as an abortifacient. The doses required for this effect can cause serious symptoms including vomiting, seizures, hallucinations, renal damage, hepatotoxicity, and shock; deaths have also occurred. Any level of internal pennyroyal oil use during pregnancy carries severe risk, and the abortifacient dose is not reliably distinguishable from the toxic or lethal dose.
8.8 Antidote and Management of Poisoning
Glutathione has been shown to detoxify the toxic metabolites of pulegone, and N-acetylcysteine should be administered in a manner similar to what is recommended for acetaminophen overdose. Data on human metabolites may provide new insights into the toxic mechanisms and treatment of pennyroyal poisoning, including the potential role of N-acetylcysteine.
References
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