A review of medicinal uses and pharmacological effects of
Mentha piperita Punit P Shah1 and P M D’Mello* Department of Pharmacognosy and Phytochemistry Prin. K. M. Kundnani College of Pharmacy, Worli, Mumbai –18 1 Research Centre, Ajanta Pharma Ltd., Mumbai *Correspondent author, E-mail: pm_dmello@rediffmail.com reddish-purple and smooth. The leaves are Abstract short 2.5-5cm long, oblong-ovate and Mentha piperita Linn. emend. Huds. is widely used in food, serrate. The flowers are purple-pinkish cosmetics and medicines. It has been proven helpful in symptomatic relief of the and appear in the summer months. The common cold. It may also decrease symptoms of irritable bowel syndrome and plant has runners above and below ground decrease digestive symptoms such as dyspepsia and nausea, although more and propagation takes place through these research is needed. It is used topically as an analgesic and to treat headaches. runners. It is originally native of Europe, Though M. piperita is on the FDA’s GRAS (Generally recognized as safe) list but Canada, and the US and have been herb has few side effects. The peppermint oil can cause heartburn or perianal naturalized in many parts of India. It is irritation, and is contraindicated in patients with bile duct obstruction, gallbladder cultivated in India, China, Europe, inflammation and severe liver damage, and caution should be taken in patients America, Australia, South Africa and some with GI reflux. Menthol products should not be used directly under the nose of other countries. The leaves and flower tops small children and infants due to the risk of apnoea. are collected as soon as flowers begin to open and dried as crude drug for its oil Keywords: Mentha piperita, Peppermint, Peppermint oil, Menthol, Medicine, and peppermint (Fleming, 1998; Wealth Toxicity. of India – Raw Materials, 1962). IPC code; Int. cl.7 ⎯ A61K 35/78, A61P1/00, A61P17/00
Introduction traditional systems of medicine. In
Ayurveda, this is an important ingredient Mentha species are used for of several compound formulations used their flavouring and medicinal properties in management of gastro-intestinal and widely throughout different countries of skin disorders. It is thought to be a natural the world. Mentha piperita Linn. hybrid between spearmint (M. spicata emend. Huds. is currently one of the Linn. emend. Nathh.) and water mint most economically important aromatic (M. aquatica Linn), the latter itself and medicinal crops. It is commonly being a hybrid of M. longifolia (Linn.) known as Peppermint, Brandy mint, Candy Huds. and M. rotundifolia (Linn.) mint, Lamb mint, Balm mint, Vilayati Huds., so M. piperita is a triple hybrid pudina or Paparaminta and belongs (Fleming, 1998; Wealth of India – Raw to the family Lamiaceae. The world Materials, 1962). production of peppermint oil is about The plant is a strongly scented, 8000 tonnes per year (Eccles, 1994). It is perennial, glabrous, herb 30-90 cm in a popular medicinal plant in several height. The square stems are usually Mentha piperita
Article Medicinal uses About 85 constituents of the oil bile was menthol glucuronide; various have been identified and a further 40 are oxidation products were also found in the Peppermint oil vapour is used as unidentified. The composition is urine (Yamaguchi et al, 1994). The an inhalant for respiratory congestion. considerably influenced by environmental oxidation products of menthol include Peppermint tea is used to treat coughs, factors like temperature, photoperiod, para-menthane-3,8-diol, para- bronchitis, and inflammation of the oral nutrition, salinity, water stress, plant age, menthane-3,9-diol, and 3,8-dihydroxy- mucosa and throat. It has traditionally harvesting and planting time (Chales para-menthane-7-carboxylic acid. been used to treat a variety of digestive et al, 1990). Flavanoids like luteolin and Additional oxidation metabolites that have complaints such as colic in infants, its 7-glucoside (cynaroside), menthoside, been identified include a primary alcohol, flatulence, diarrhoea, indigestion, nausea isorhoifolin and others including a a triol, and hydroxy acids (Madyastha & and vomiting, morning sickness and number of highly oxygenated flavones have Srivatsan, 1988; Yamaguchi et al, 1994). anorexia, and as a spasmolytic to reduce been reported (Orani et al, 1991; Rastogi When 750 mg (− − )-menthol was given gas and cramping. The oil is also used in et al, 1990). orally to three human volunteers, followed toothache, rheumatism, muscular pains Phenolic acids including caffeic, by oral or intravenous administration of and to relieve menstrual cramps. M. chlorogenic and rosmarinic acid and 200 mg [6-13C]-glucuronolactone or [6- piperita is currently used to treat irritable "Pseudotannins" derived from them are 13C]-sodium glucuronate, menthyl bowel syndrome, Crohn’s disease, reported to be present. Triterpenes in glucuronide was excreted for two days, in ulcerative colitis, gallbladder and biliary small amounts including squalene, average daily yields ranging from approx- tract disorders, and liver complaints α-amyrin, urosolic acid and sitosterol and imately 27 to 84% (Eisenberg et al, 1955). (Fleming, 1998; Tyler, 1992; Robbers & other constituents, azulene and minerals Tyler, 1999). are also reported (Lucida & Wallace, Pharmacological effects 1998). Chemical composition Peppermint oil possesses greater Respiratory antihydrolytic effect than the commercial The major constituent reported preservative such as butylated Inhibition of respiration ⎯ is volatile oil of which the principal hydroxytoluene (Singh et al, 1998). Menthol stimulates upper airway cold component is usually (− − ) menthol, receptors that causes a reflex inhibition Pharmacokinetics of respiration and inhibits upper airway together with menthol stereoisomers such as (+) neomenthol and (+) isomenthol. In a pharmacokinetic study of accessory respiratory muscle activity. In Other monoterpenes include menthone treatment with peppermint oil in enteric- guinea pigs and dogs, but not cats, (10-40%), menthyl acetate (1-10%), coated capsules (containing 91-97 mg menthol causes reflex inhibition of menthofuran (1-10%), cineol (eucalyptol, menthol) or soft gelatin capsules urinary respiration (Orani et al, 1991; Davies & 2-13%) and limonene (0.2-6%). excretion of menthol glucuronide Eccles, 1987). Monoterpenes like pinene, terpinene, represented 17% of the dose from two Nasal decongestant ⎯ In cats myrcene, β-caryophyllene, piperitone, coated capsules and 29% of the dose from and dogs, vaporized menthol stimulated piperitenone, piperitone oxide, pulegone, the capsules 24 hr after administration cold receptors in the respiratory tract eugenol, menthone, isomenthone, (Somerville et al, 1984). When an (Schafer et al, 1986). In a double blind carvone, cadinene, dipentene, linalool, enteric-coated capsule containing 130 mg randomized controlled trial, 62 subjects α-phellendrene, ocimene, sabinene, peppermint oil was fed to four subjects, with nasal congestion secondary to terpinolene, γ-terpinene, fenchrome, the average 14 hr urinary excretion of common cold infections were given a p-menthane and β-thujone are also menthol glucuronide was 40% of the dose lozenge containing 11 mg menthol or present in small quantities (Baslas, 1977; (range, 20-64%) (Kaffenberger & Doyle, placebo. The subjects given the menthol Baslas & Saxena, 1984). 1990). The major metabolite found in the reported a significant improvement in the
Article sensation of nasal airflow after ten minutes induced spasm on the sphincter of Oddi 1984; Rees et al, 1979; Nash et al, 1986). (Eccles et al, 1990). (Giachetti et al, 1987). In two double blind, placebo- Antitussive ⎯ In a randomized In 20 subjects who were controlled crossover studies, 16 to 29 trial, 20 healthy subjects received a citric undergoing colonoscopy, administration subjects with active IBS were given either acid cough challenge every hour for five of peppermint oil during the procedure enteric-coated peppermint oil (one or two hours. Five minutes before each challenge relieved colon spasm within 30 seconds 0.2 ml capsules three times daily) or the subjects inhaled either menthol in in each patient (Leicester & Hunt, 1982). placebo for three to four weeks. The eucalyptus oil or one of two placebos Similarly, in a placebo controlled trial in peppermint oil capsules significantly (pine oil or air). Menthol inhalation six adults, injection of 0.2 ml peppermint increased the feeling of well being and caused a reduction in evoked cough when oil suspension into the colon led to a decreased abdominal pain compared to compared with either placebo (Morice statistically significant decrease in motor placebo. There was no significant effect et al, 1994). activity at two minutes and lasting 7-23 on stool frequency. The frequency of minutes (Duthie, 1981). symptom-free days increased and severe Gastrointestinal/Hepatic disorders In a double blind, placebo- symptoms decreased in the peppermint oil Digestive aid ⎯ In a blinded controlled randomized study of 141 group but the data were not statistically controlled study, 20 healthy males (ages patients receiving a Barium enema, those significant. Two subjects developed 21-23 and 34-35) and six subjects with who had 40 ml of topical peppermint oil heartburn (Dew et al, 1984; Rees et al, non-obstructive dyspepsia were fed a radio preparation added to the Barium 1979). labeled solid test meal with and without suspension reported a significantly lower In a double blind clinical trial, peppermint oil (25 ml of water with 0.2 rate of residual spasm compared to 34 patients with IBS in whom pain was a ml of peppermint oil). After administration placebo group (64% vs. 35%). In patients prominent symptom took two peppermint of peppermint oil, gastric emptying rate with diverticular disease, 72% were oil (0.2 mg) capsules or placebo three accelerated in both normal and patients spasm-free, compared to 21% of times daily for two and four weeks. The with dyspepsia. None of the volunteers diverticular disease patients in the placebo patients’ assessment of their overall complained of any side effects (Dalvi group. No adverse effects were reported symptoms showed no significant et al, 1991). (Sparks et al, 1995). difference between peppermint oil and Anti-emetic ⎯ In a placebo- Irritable bowel syndrome placebo (Nash et al, 1986). controlled study of gynaecological surgery (IBS) ⎯ In rat small intestine, The enteric-coated peppermint patients, there was a statistically significant peppermint oil at concentrations of 0.5 capsules were found to dissolve in the effect of peppermint in reducing and 1 mg/ml inhibited enterocyte glucose colon and gelatin-coated peppermint postoperative nausea (Tate, 1997). uptake via a direct action at the brush capsules in the stomach of human Antispasmodic ⎯ Peppermint border membrane. Inhibition of secretion volunteers. To be effective in the treatment relaxes gastro-intestinal smooth muscle by by serosal peppermint oil is consistent of spastic colon syndromes, the oil must reducing calcium influx in both guinea pig with a reduced availability of calcium reach the colon in an unmetabolized state large intestine and rabbit jejunum (Hills (Beesley et al, 1996). (Somerville et al, 1984). & Aaronson, 1991; Taylor et al, 1983). A meta-analysis of four In human volunteers, both Peppermint oil and menthol have calcium randomized controlled studies indicated enteric-coated (Enteroplant®) and non- channel blocking activity in rat and guinea that peppermint oil could be efficacious enteric-coated preparations (a combina- pig atrial and papillary muscle, rat brain for the symptoms of IBS. However, it has tion of peppermint oil 90 mg and 50 mg synaptosomes, and chick retinal neurones been noted that methodological flaws in of caraway oil) showed a decrease in the (Taylor et al, 1983; Taylor, 1984). the studies prevented this number of contractions and contraction In anesthetized guinea pigs, recommendation beyond a reasonable amplitudes during the various phases of the peppermint oil resolved a morphine- doubt (Pittler & Ernst, 1998; Dew et al, MMC (Migrating Motor Complex).
Article Non-enteric-coated preparations showed mannitol, indomethacin, morphine pyrogenes, Escherichia coli, their effects mainly during the second hydrochloride and propranolol (Katayama Bacillus subtilis and Proteus MMC after administration. Enteric-coated et al, 1992; Morimoto et al, 1993; Kunta vulgaris (Kokate & Varma, 1970; and non-enteric-coated peppermint- et al, 1997). In low concentrations, Sawhney et al, 1977). It possesses caraway oil combinations are safe topical application of menthol causes a repellent activity against Tribolium preparations, acting locally to cause cooling sensation; while in high castaneum and is moderately effective smooth muscle relaxation (Micklefield concentrations it causes irritation and fumigant on both Callosobruchus et al, 2000). local anaesthesia (Eccles, 1994). maculatus and T. castaneum (Tripathi Biliary disorders ⎯ In animal In a three-fold crossover clinical et al, 2000). Moderate antimyotic studies, flavanoids found to possess trial on the arms of 15 healthy males, property against Aspergillus cholerectic effect (Lucida & Wallace, topical application of menthol-reduced fumigatus, Candida albicans, 1998). Menthol and related terpenes exert histamine-induced itch (Kokate & Varma, Geotrichum candidum and a choleretic effect. Several clinical studies 1970). Rhodotarula rubra (Blaszcy et al, with the drug Rowachol® (a mixture of Local anaesthetic ⎯ Both the 2000), Phytophthora cinnamoni, six cyclic monoterpenes: menthol, enantiomers of menthol (0.0001 mg/ml) Pyrenochaeta lycopersici and menthone, pinene, borneol, camphene, drastically reduced the electrically evoked Verticillium dahliae (Giamperi et al, and cineol) have shown success in the contractions of rat phrenic nerve 2002) has been reported. Peppermint oil treatment of patients with cholesterol hemidiaphragm while increases the showed antifungal activity against stones in their gallbladders and bile ducts number of stimuli in rabbit necessary to Aspergillus niger, Alternaria (Somerville et al, 1985; Ellis & Bell, 1981; provoke the reflex in a dose dependent alternata and Fusarium sp. by agar Ellis et al, 1984; Doran et al, 1979). manner (Thorup et al, 1983a,b; Galeotti well diffusion method (Aqil et al, 2000). In a controlled prospective et al, 2001). double blind trial, 23 patients with Radioprotective cholesterol gallstones were treated with Anti-inflammatory ursodeoxycholic acid (UDCA) (11.1 mg/ M. piperita leaf extract pre- kg per day) or Ursomenth, a combination The ethanolic extract possesses treatment provides protection against of UDCA plus menthol (4.75 mg/kg per anti-inflammatory effect in acute (xylene radiation induced alterations in intestinal day). After 17 months, complete induced ear oedema) and chronic (cotton mucosa of swiss albino mice. A significant dissolution had occurred in 53% of the pellet granuloma) inflammation (Atta & promotion was obtained in various Ursomenth group, versus 38% of the UDCA Alkofahi, 1998). hematological parameters and modulates group (Leuschner et al, 1988). Azulene found in oil of activity of serum phosphates in albino peppermint have shown to have anti- mice against γ-radiation (Samarth et al, Skin and mucus membranes inflammatory effects in laboratory animals 2001, 2002; Tripathi et al, 1999). (Lucida & Wallace, 1998). Analgesic and coolant ⎯ Toxicity and contraindications Peppermint oil stimulates cold receptors Antimicrobial on the skin and dilates blood vessels, Potentially toxic compounds in causing a sensation of coldness and an The peppermint oil exerts peppermint are pulegone and menthol. analgesic effect. Menthol is a topical antidermatophytic activity against (+) and Pulegone, the toxic compound in vasodilator that enhances the absorption −) strains of Narinizzia fulva and N. (− pennyroyal, is also found in peppermint of other topical skin medications. On gypsea (Gautam et al, 1980) and in much smaller proportions. In rats, hairless mice, menthol (1-5% w/v) antibacterial activity against doses of 80 and 160 mg of pulegone for enhances the absorption of cortisone, Staphylococcus aureus, S. 28 days caused atonia, weight loss,
Article decreased blood creatinine content, and has shown no gross toxic effect (Eccles, J Ethnopharmacol, 1998, 60, histopathological changes in the liver and 1994). Peppermint oil is contraindicated 1179. the white matter of the cerebellum. in obstruction of the bile ducts, gallbladder 3. Baslas RK, Essential oil of Mentha Menthol causes hepatocellular changes in inflammation, and severe liver damage piperita (L) raised in Kumaon rats. In rats, peppermint oil caused cyst- (Lucida & Wallace, 1998). Patients with region (India), Nat Appl Sci like changes in the white matter of the achlorhydria should use peppermint oil Bull, 1977, 29 (2), 75. cerebellum and nephropathy at doses of only in enteric-coated capsules (Rees 4. Baslas RK and Saxena S, 40-100 mg/kg per day for 28-90 days et al, 1979). Patients with GI reflux should Chromatographic analysis of (Spindler & Madson, 1992; Thorup et al, use caution because peppermint may dementholised essential oil of 1983a,b). make GI reflux symptoms worse. Caution Mentha piperita, Indian J Phys Direct application of peppermint is recommended in patients with hiatal Nat Sci, 1984, 4A, 32. oil to the nasal area or chest to infants hernia, kidney stones, or GI reflux. should be avoided because of the risk of 5. Beesley A, Hardcastle J, Hardcastle apnoea, laryngeal and bronchial spasms, Conclusion PT and Taylor CJ, Influence of acute respiratory distress with cyanosis peppermint oil on absorptive and and respiratory arrest (Blake et al, It can be concluded that with its secretary processes in rat small 1993). intestine, Gut, 1996, 39, 214-219. vast and diversified pharmacological potentials M. piperita has a strong future 6. Blake KD, Fertleman CR and Meates Acute toxicity in the world market. This plant is now MA, Dangers of common cold well-acclimatized and cultivated in treatments in children [letter], Adverse reactions to enteric- different parts of India and enjoys a strong Lancet, 1993, 341 (8848), 640, coated peppermint oil capsules are rare export potential for the volatile oil 842. but can include hypersensitivity reaction, extracted from it. Various formulations 7. Blaszcy KT, Krzyzonowaska J and contact dermatitis, abdominal pain, heart like Pudin Hara ® for gastro-intestinal Lamber Zarawsaka E, Screening for burn, perianal burning, bradycardia and disturbances like flatulence and antimycotic properties of 56 muscle tremor (Rees et al, 1979; Nash indigestion and Itch-gard ® for skin traditional Chinese drugs, et al, 1986; Weston, 1987; Bromm et al, disorders are available in the market. Phytother Res, 2000, 14, 1995). The excessive inhalation of 210-212. mentholated preparation has caused reversible nausea, anorexia, cardiac References 8. Bromm B, Scharein E, Darsow U problems, ataxia, and other CNS problems, and Ring J, Effects of menthol and which are thought to be due to the 1. Aqil F, Beng AZ and Ahmed L, In cold on histamine-induced itch and presence of volatile oils. There is a case vitro toxicity of plant essential oil skin reactions in man, Neurosci report of a 13- year-old boy who, following against soil fungi (National seminar Lett, 1995, 187, 157-160. inhalation of 5 ml of Olbas oil (containing on the Frontiers of Research and 9. Charles DJ, Jolly RJ and Simonj JE, 200 mg menthol) instead of the Development in medicinal plants, Effect of osmotic stress on the recommended few drops, experienced Sept 16-18, 2000, CIMAP, Lucknow, essential oil content and ataxia, confusion, euphoria, nystagmus, Abstract No P-56), J Med Arom composition of peppermint, and diplopia (O’Mullane et al, 1982). Plant Sci, 2000, 22 (Suppl 1), 44. Phytochemistry, 1990, 29, 2. Atta AH and Alkofahi A, 2837-2840. Chronic toxicity 10. 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Adulterants of Peppermint oil
Total amount of menthol is the most important indication to examine the peppermint oil. The English oil contains 60 to 70 per cent of menthol, the Japanese oil containing 85 per cent, and the American about 50 per cent. The odour and taste also afford a good indication of the quality of the oil, and help to distinguish between English, American and Japanese oils. The oils produced from M. arvensis var. piperascens, M. arvensis var. glabrata and M. incana are greatly inferior to those distilled from M. piperita, but have the advantage of containing a large proportion of menthol. M. arvensis (Hindi-Pudina), has to be carefully removed from the fields of peppermint to avoid spoiling of the flavour of the peppermint oil when the herb is distilled. Adulteration of American Peppermint oil with dementholized Japanese oil, known as menthene, which is usually cheaper than American oil, is frequently practiced. Camphor oil, Cedarwood oil and oil of African Copaiba are also occasionally used as adulterants of Peppermint oil. Some times the oil is adulterated with one-third part of rectified spirit, which may be detected by the milkiness produced when the oil is agitated by water. Oil of Rosemary and oil of Turpentine are occasionally used for the same purpose. If the oil contains turpentine it will explode with iodine. If quite pure, it dissolves in its own weight of rectified spirits of wine. (http://www.botanical.com/ botanical/mgmh/m/mints-39.html).