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Pennyroyal

Scientific Name(s): Hedeoma pulegioides (L.) Persoon (American), Mentha pulegium L. (European)
Common Name(s): American pennyroyal, European pennyroyal, False pennyroyal, Mosquito plant, Pudding grass, Squawmint

Clinical Overview

See also: Embeline

Use

Clinical studies are lacking to provide guidance on therapeutic applications due to the plant’s toxicity.

Dosing

Pennyroyal oil is not recommended for internal or topical use. There are no clinical studies of pennyroyal herbal tea to provide dosing guidance. Pulegone-free preparations should be used.

Contraindications

Pennyroyal oil is not recommended for internal or topical use.

Pregnancy/Lactation

Avoid use. Abortifacient, hepatotoxic, neurotoxic, and carcinogenic adverse effects have been reported.

Interactions

None well documented.

Adverse Reactions

Pennyroyal oil is not recommended for internal or topical use due to abortifacient, hepatotoxic, neurotoxic, and carcinogenic properties. Although pennyroyal herbal teas have generally been used without reported adverse effects, pulegone-free preparations are recommended. Allergic reactions to the plant, including contact dermatitis and generalized urticaria, have been reported.

Toxicology

The toxicity of pennyroyal oil is well recognized, with many documented reports of adverse events and fatalities. In humans, consumption of 10 mL of the oil has resulted in moderate to severe toxicity, with case reports of fatalities 1 to 2 hours after consumption of 15 mL. Symptoms of toxicity include abdominal cramping and pain, nausea, vomiting, rash, dizziness, alternating lethargy and agitation and other CNS symptoms (including seizures), renal and hepatic failure, and disseminated intravascular coagulation. Early administration of acetylcysteine to restore glutathione levels and of cytochrome P450 (CYP-450) activators cimetidine and disulfiram may counteract the putative effects of pulegone.

Botany

American and European species of pennyroyal plant are members of the mint family (Lamiaceae family [formerly Labiatae]), and both are referred to as "pennyroyal." H. pulegioides (American pennyroyal) grows in woods throughout most of the northern and eastern United States and Canada, while M. pulegium is found in parts of Europe. Pennyroyal is a perennial creeping herb with small lilac flowers at the stem ends. It can grow to be 30 to 50 cm in height. Like other mint family members, the grayish-green leaves are very aromatic.1, 2 A synonym of H. pulegioides is Melissa pulegioides L. A synonym of M. pulegium is Pulegium vulgare Mill.

History

Use of pennyroyal was recorded as early as the first century AD, by the Roman naturalist Pliny and the Greek physician Dioscorides. In the 17th century, English herbalist Nicholas Culpeper described the plant's role in women's ailments, venomous bites, and digestion. European settlers used the plant for respiratory ailments, mouth sores, and female disorders.3 The plant's oil has been used as a flea-killing bath, hence the name "pulegioides" (from the Latin word meaning flea), and has been used externally as a rubefacient. The oil has also been frequently used among natural health advocates as an abortifacient and to induce delayed menses. The oil and infusions of the leaves have been used to treat weakness and stomach pains, among other indications.2, 4

Chemistry

The leaves and flowering tops are the source of the essential oil, which has a concentration of 1% to 2%, depending on the genus. The phenolic composition of the aqueous extract has been described and includes flavonoids (luteolin, apigenin, naringenin, catechin, rutinoside, jaceosidin, and others) and phenolic acids (including caffeic, vanillic, ferulic, rosmarinic, and lithospermic).5, 6, 7 Antioxidant activity of pennyroyal tea due to the phenolic content has been demonstrated.5

The essential oil is rich in monoterpenes, especially pulegone (also found in peppermint oil) and its metabolite menthofuran, with piperitone oxide, isopulegol, piperitone, and piperitenone also described, as well as monoterpene hydrocarbons and sesquiterpenoids.7, 8 Techniques for quantification of components have been described.8, 9

Uses and Pharmacology

Insecticide/Antimicrobial activity

Animal data

Studies suggest insect repellant and insecticidal activity, probably due to the essential oil vapor. Although activity against head lice (Pediculus humanus capitis) has been demonstrated,10 topical application of pennyroyal is not recommended due to toxicity related to skin absorption. The moderate repellant activity observed against wasps may be due to pulegone, eugenol, citral, and other chemicals.11

Pennyroyal (dried, whole plant) administered to chickens in their feed reduced the presence of intestinal Escherichia coli, with no apparent adverse effects.12

Clinical data

Clinical studies are lacking to provide guidance on therapeutic applications due to the plant's toxicity.

Dosing

Pennyroyal oil is not recommended for internal or topical use.2, 13, 14 There are no clinical studies of pennyroyal herbal tea to provide dosing guidance. Pulegone-free preparations should be used. One safety assessment of peppermint oil indicated that the concentration of pulegone should not exceed 1%.15 Pennyroyal is also present in certain multi-ingredient preparations.16

Pregnancy / Lactation

Avoid use. Abortifacient, hepatotoxic, neurotoxic, and carcinogenic adverse effects have been reported.2, 13, 14, 16, 17

In a study using isolated rat uterine myometrial tissue, Mentha pulegium oil’s inhibition of contractile activity was similar to that of the calcium channel blocker nifedipine.18

Interactions

None well documented. Case reports are lacking.

Adverse Reactions

Pennyroyal oil is not recommended for internal or topical use. Abortifacient, hepatotoxic, neurotoxic, and carcinogenic adverse effects have been reported.2, 13, 14, 16, 17

Although pennyroyal herbal teas have generally been used without reported adverse effects, pulegone-free preparations are recommended.2 Allergic reactions to the plant, including contact dermatitis and generalized urticaria, have been reported.19, 20

Toxicology

The toxicity of pennyroyal oil is well recognized, with many documented reports of adverse events and fatalities. In humans, consumption of 10 mL of the oil has resulted in moderate to severe toxicity, with case reports of fatalities 1 to 2 hours after consumption of 15 mL.21 In rats, the median lethal dose (LD50) of pennyroyal essential oil is reported to be 400 mg/kg.2

Toxicity is likely the result of the direct action of pulegone on glutathione, as well as the action of its toxic metabolite menthofuran.14, 21, 22, 23 Symptoms of toxicity include abdominal cramping and pain, nausea, vomiting, rash, dizziness, alternating lethargy and agitation and other CNS symptoms (including seizures), renal and hepatic failure, and disseminated intravascular coagulation.2, 14, 21, 22, 23

Early administration of acetylcysteine to restore glutathione levels and of cytochrome P450 (CYP-450) activators cimetidine and disulfiram may counteract the putative effects of pulegone based on one case report.13, 21 Studies in rodents have suggested that CYP-450 activators cimetidine and disulfiram may also counteract the putative effects of pulegone on the liver.23, 24

Evidence of cytotoxicity in rodents has been reported, with an increase in liver neoplasms observed. Equivocal results for mutagenicity of pulegone have suggested that the chemical is a non-DNA–reactive carcinogen.25

References

1. Hedeoma pulegioides (L) Pers. USDA, NRCS. 2015.The PLANTS Database (http://plants.usda.gov, 15 December). National Plant Data Center, Greensboro, NC 27401-4901 USA.
2. Duke J, Bogenschutz-Godwin M, duCellier J, Duke P. Handbook of Medicinal Herbs. 2nd ed. Boca Raton, FL: CRC Press; 2002.
3. Cartwright L, Low T, Rodd T, et al, eds. Pennyroyal. Magic and Medicine of Plants. Sydney, Australia: Reader's Digest; 1994:278.
4. Da Legnano LP. The Medicinal Plants [in Italian]. Rome, Italy: Edizioni Mediterranee; 1973.
5. Kogiannou DA, Kalogeropoulos N, Kefalas P, Polissiou MG, Kaliora AC. Herbal infusions; their phenolic profile, antioxidant and anti-inflammatory effects in HT29 and PC3 cells. Food Chem Toxicol. 2013;61:152-159.23712099
6. Ferreres F, Bernardo J, Andrade PB, Sousa C, Gil-Izquierdo A, Valentão P. Pennyroyal and gastrointestinal cells: Multi-target protection of phenolic compounds against t-BHP-induced toxicity [published online April 29, 2015]. RSC Adv. 2015;5(52):41576-41584.10.1039/C5RA02710A
7. Duke J. Handbook of Biologically Active Phytochemicals and Their Activities. Boca Raton, FL: CRC Press Inc; 1992.
8. Díaz-Maroto MC, Castillo N, Castro-Vázquez L, González-Viñas MA, Pérez-Coello MS. Volatile composition and olfactory profile of pennyroyal (Mentha pulegium L.) plants. Flavour Frag J. 2007;22(2):114-118.
9. Ferguson LJ, Lebetkin EH, Lih FB, et al. 14C-labeled pulegone and metabolites binding to alpha2u-globulin in kidneys of male F-344 rats. J Toxicol Environ Health A. 2007;70(17):1416-1423.17687727
10. Yang YC, Lee HS, Clark JM, Ahn YJ. Insecticidal activity of plant essential oils against Pediculus humanus capitis (Anoplura: Pediculidae). J Med Entomol. 2004;41(4):699-704.15311463
11. Zhang QH, Schneidmiller RG, Hoover DR. Essential oils and their compositions as spatial repellents for pestiferous social wasps. Pest Manag Sci. 2013;69(4):542-552.23081867
12. Erhan MK, Bölükbasi SC, Ürüsan H. Biological activities of pennyroyal (Mentha pulegium L.) in broilers. Livest Sci. 2012;146(2-3):189-192.
13. Anderson IB, Mullen WH, Meeker JE, et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med. 1996;124(8):726-734.8633832
14. Samuels N, Finkelstein Y, Singer SR, Oberbaum M. Herbal medicine and epilepsy: Proconvulsive effects and interactions with antiepileptic drugs. Epilepsia. 2008;49(3):373-380.17941846
15. Nair B. Final report on the safety assessment of Mentha Piperita (Peppermint) oil, Mentha Piperita (Peppermint) leaf extract, Mentha Piperita (Peppermint) leaf, and Mentha Piperita (Peppermint) leaf water. Int J Toxicol. 2001;20(suppl 3):61-73.11766133
16. Ciganda C, Laborde A. Herbal infusions used for induced abortion. J Toxicol Clin Toxicol. 2003;41(3):235-239.12807304
17. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
18. Soares PM, Assreuy AM, Souza EP, et al. Inhibitory effects of the essential oil of Mentha pulegium on the isolated rat myometrium. Planta Med. 2005;71(3):214-218.15770540
19. Pérez-Calderón R, Gonzalo-Garijo A, Bartolomé-Zavala B, Lamilla-Yerga A, Moreno-Gastón I. Occupational contact urticaria due to pennyroyal (Mentha pulegium). Contact Dermatitis. 2007;57(4):285-286.17868232
20. Roé E, Serra-Baldrich E, Dalmau J, et al. Mentha pulegium contact dermatitis. Contact Dermatitis. 2005;53(6):355.16364129
21. Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013;37(1):3-17.23121117
22. Gordon P, Khojasteh SC. A decades-long investigation of acute metabolism-based hepatotoxicity by herbal constituents: a case study of pennyroyal oil. Drug Metab Rev. 2015;47(1):12-20.25512112
23. Seeff LB. Herbal Hepatotoxicity. Clin Liver Dis. 2007;11(3):577-596.17723921
24. Sztajnkrycer MD, Otten EJ, Bond GR, Lindsell CJ, Goetz RJ. Mitigation of pennyroyal oil hepatotoxicity in the mouse. Acad Emerg Med. 2003;10(10):1024-1028.14525732
25. Da Rocha MS, Dodmane PR, Arnold LL, et al. Mode of action of pulegone on the urinary bladder of F344 rats. Toxicol Sci. 2012;128(1):1-8.22499580

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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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