Pennyroyal

Summary and Pharmaceutical Comment

Interest in pennyroyal has focused on the toxicity associated with the volatile oil. No documented reports of the pharmacological actions exhibited by the herb were located. In view of its potential toxicity, pennyroyal oil is not suitable for internal or external use.

Species (Family)

*Mentha pulegium L. (Labiatae/Lamiceae)

†Hedeoma pulegioides (L.) Pers.

Synonym(s)

*Pulegium vulgare Mill., P. parviflorum (Req.) Samp. pro parte

†Melissa pulegioides L., Squaw Mint

Part(s) Used

Herb

Pharmacopoeial and Other Monographs

BHP 1983(G7)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

Pennyroyal is not included in the GSL.(G37)

P

Constituents

The following is compiled from several sources, including General References G22, G48 and G58.

Volatile oils 1–2%. Pulegone is the principal component (60– 90%); others include menthone, iso-menthone, 3-octanol, piperitenone and trans-iso-pulegone.

Food Use

Pennyroyal is not commonly used in foods. It is listed by the

Council of Europe as a natural source of food flavouring (category N3).(G16) This category indicates that there is insufficient

information available for an adequate assessment of toxicity

(but see Side-effects, Toxicity). Previously, in the USA, pennyroyal has been permitted for use in foods.(G65)

Herbal Use

Pennyroyal is stated to possess carminative, antispasmodic, diaphoretic and emmenagogue properties, and has been used topically as a refrigerant, antiseptic and insect repellent. Traditionally, it has been used for flatulent dyspepsia, intestinal colic, common cold, delayed menstruation, and topically for cutaneous eruptions, formication and gout.(G7)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below. Pennyroyal oil is not suitable for internal or external use.

Herb 1–4 g as an infusion three times daily.(G7)

Liquid extract 1–4 mL (1 : 1 in 45% alcohol) three times daily.(G7)

Pharmacological Actions

None documented.

Clinical studies

There is a lack of clinical research assessing the effects of pennyroyal.

Side-effects, Toxicity

Clinical data

The toxicity of pennyroyal oil is well recognised and human fatalities following its ingestion as an abortifacient have been reported.(1–3) Symptoms reported following ingestion of the oil include abdominal pain, nausea, vomiting, diarrhoea, lethargy and agitation, pyrexia, raised blood pressure and pulse rate, and generalised urticarial rash. Generally, doses required for an abortifacient effect are also toxic and fatalities have involved both nephrotoxicity and hepatotoxicity.(2–4) Doses of one ounce and 30 mL(1–3) have proved fatal, whereas individuals have recovered following unsuccessful abortion attempts involving the ingestion of 7.5 mL oil.(3) The mechanism of hepatotoxicity for pennyroyal is not known.(2) A direct hepatoxic action has been suggested for the ketone component, pulegone.(2) Alternatively, metabolic conversion of pulegone to a reactive intermediate, a furan or epoxide, has been proposed.(2)

Preclinical data

Acute LD50 values for pennyroyal oil are documented as 0.4 g/kg (oral, rats) and 4.2 g/kg (dermal, rabbits).(4) The oil is nonor

moderately irritating, non-sensitising and non-phototoxic.(4) Acute LD50 values documented for pulegone, the principal oil component, are, not suprisingly, similar to those for the oil: 0.47 g/ kg (oral, rats), 3.09 g/kg (dermal, rabbits).(5) Steroid (pregneno- lone-16a-carbonitrile) treatment has reduced hepatotoxicity

Figure 1 Selected constituents of pennyroyal.

observed in female rats fed pulegone, whereas triamcinolone has increased it.(5) Toxicity of pulegone is unaffected by partial hepatectomy or ligation of the common bile duct, while partial nephrectomy intensified toxicity.(5)

Contra-indications, Warnings

Pennyroyal oil is irritant and instances of hepatotoxicity and nephrotoxicity have been documented following its ingestion.

Both the internal and external use of pennyroyal oil are contraindicated.(G58)

Pregnancy and lactation Pennyroyal is contra-indicated in pregnancy.(G7) Traditionally, it has been employed as an abortifa-

Pennyroyal 471

cient; fatalities have resulted from the doses of oil required to exert an abortifacient effect.

References

1Vallance WB. Pennyroyal poisoning. A fatal case. Lancet 1955; ii: 850– 851.

2 Sullivan JB et al. Pennyroyal oil poisoning and hepatotoxicity. JAMA 1979; 242: 2873.

3Gunby P. Plant known for centuries still causes problems today. JAMA 1979; 241: 2246–2247.

4 Opdyke DLJ. Pennyroyal oil european. Food Cosmet Toxicol 1974; 12: 949–950.

5Opdyke DLJ. Fragrance raw materials monographs: d-pulegone. Food Cosmet Toxicol 1978; 16: 867–868.

Summary and Pharmaceutical Comment

Limited information is available on the chemistry of pilewort. Little scientific information was located to justify the herbal uses, although antihaemorrhoidal activity has been documented for the saponin constituents in preclinical investigations. There is a lack of clinical research assessing the efficacy and safety of pilewort. In view of the toxic and irritant properties stated for protoanemonin, the excessive use of pilewort and use during pregnancy and lactation should be avoided.

Species (Family)

Ranunculus ficaria L. (Ranunculaceae)

Synonym(s)

Ficaria, Ficaria ranunculoides Roth, F. degenii Hervier, F. nudicaulis A. Kern., F. verna Huds., F. vulgaris A. St.-Hil., Lesser Celandine, Ranunculus

Part(s) Used

Herb

Pharmacopoeial and Other Monographs

BHP 1996(G9)

Martindale 35th edition(G85)

PLegal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General References G40 and G42.

Lactones Anemonin (dimer), protoanemonin (precursor to anemonin).

Triterpenoids Glycosides based on the sapogenins hederagenin and oleanolic acid, with arabinose, glucose and rhamnose, as sugar moieties.(1)

Other constituents Tannin and ascorbic acid (vitamin C).

Food Use

Pilewort is not used in foods.

Herbal Use

Pilewort is stated to possess astringent and demulcent properties. Traditionally, it has been used for haemorrhoids, and specifically for internal or prolapsed piles with or without haemorrhage, by topical application as an ointment or a suppository.(G7, G64)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in older and contemporary standard herbal and/or

pharmaceutical reference texts are given below. Another source states that pilewort is not suitable for internal use.(G49)

Dried herb 2–5 g as an infusion three times daily.(G7)

Liquid extract 2–5 mL (1 : 1 in 25% alcohol) three times daily.(G7)

Pilewort Ointment (BPC 1934) 30% fresh herb in benzoinated lard.

Pharmacological Actions

In vitro and animal studies

Local antihaemorrhoidal activity has been documented for the saponin constituents.(1) Antibacterial and antifungal properties have been documented for both anemonin and protoanemonin,

although anemonin is reported to exhibit much weaker activi-

ty.(G33, G48)

The reported presence of tannin constituents(G42) supports the reputed astringent activity of pilewort, although no pharmacological studies were located.

Clinical studies

There is a lack of clinical research assessing the effects of pilewort and rigorous randomised clinical trials are required.

Side-effects, Toxicity

There is a lack of clinical safety and toxicity data for pilewort and further investigation of these aspects is required.

The sap of pilewort is stated to be irritant.(G51) Protoanemonin is stated to be an acrid skin irritant, although it is readily converted into the inactive dimer anemonin.(G33) Protoanemonin is stated to have a marked ability to combine with sulfhydryl (-SH) groups and it is thought that the toxic subdermal properties of

Figure 2 Pilewort (Ranunculus ficaria).

Pilewort 473

Figure 3 Pilewort – dried drug substance (herb).

protoanemonin may depend on the inactivation of enzymes containing -SH groups.(G33) An LD50 value (mice, intraperitoneal

injection) for anemonin has been reported as 150 mg/kg body weight.(G48)

Contra-indications, Warnings

Pilewort is not recommended for internal consumption.(G49) Topical use of pilewort may cause irritant skin reactions.

Pregnancy and lactation The safety of pilewort has not been established. In view of this, the use of pilewort during pregnancy and lactation should be avoided.

Reference

1Texier O et al. A triterpenoid saponin from Ficaria ranunculoides tubers. Phytochemistry 1984; 23: 2903–2905.