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Improved performance on clerical tasks associated with administration of peppermint odor.

Previous research indicates the presence of certain odors is associated with enhanced task performance. The present study investigated use of peppermint odor during typing performance, memorization, and alphabetization. Participants completed the protocol twice--once with peppermint odor present and once without. Analysis indicated significant differences in the gross speed, net speed, and accuracy on the typing task, with odor associated with improved performance. Alphabetization also improved significantly under the odor condition but not typing duration or memorization. These results suggest peppermint odor may promote a general arousal of attention, so participants stay focused on their task and increase performance.

Adult↗

[Aromatic and polyphenolic composition of infused peppermint, Mentha x piperita L].

The qualitative and quantitative composition of the main aromatic and polyphenolic constituents of Mitcham type peppermint (Mentha x piperita L.) tisane, were examined and compared with those of leaves before and after infusion. The original peppermint leaves contained 2.4% essential oil of which menthol was 0.99%, total polyphenolic compounds 19% and total flavonoid compounds 12% comprising eriocitrin 7%, luteolin-7-rutinoside 1.5%, hesperidoside 0.6% and total hydroxycinnamic compounds 7% (rosmarinic acid 1.4%). The tisane contained 21% of the original essential oil corresponding to 25 mg/l, with increased alcohol and ketone contents and lower contents of hydrophobic terpenecarbons, oxides and esters. It contained also a high proportion of the polyphenolic compounds (about 750 mg/l) corresponding to an extraction yield of 75%. In consequence the monograph "Peppermint leaf" of the Pharmacopoeia should be amended.

Oils, Volatile↗

Efficacy of a fixed peppermint oil/caraway oil combination in non-ulcer dyspepsia.

The efficacy and safety of the standardized herbal combination preparation of Enteroplant, consisting of peppermint oil (90 mg) and caraway (50 mg) in an enteric coated capsule, have been studied in a double-blind, placebo-controlled multicentre trial in patients with non-ulcer dyspepsia. A total of 45 patients were included in the trial after thorough physical and gastro-enterological examination. The primary outcome variables were the change in the intensity of pain and the global clinical impression (Clinical Global Impression [CGI], Item 2), which were evaluated for 39 patients (test preparation: 19, placebo: 20). After four weeks of treatment both target parameters were significantly improved for the group of patients treated with the peppermint oil/caraway oil combination compared to the placebo group (p = 0.015 and 0.008, respectively). Before the start of treatment all patients in the test preparation group reported moderate to severe pain, while by the end of the study 63.2% of these patients were free of pain. The pain symptoms had improved in a total of 89.5% of the patients in the active treatment group. After 4 weeks the Clinical Global Impressions were improved for 94.5% of the patients treated with the peppermint oil/caraway oil combination. The trial medication was also superior to placebo with respect to pain frequency, medical prognosis, the severity of the disorder and the efficacy index (CGI, Items 1 and 3), which were adopted as secondary end-points for evaluation of efficacy. There were similarly favourable findings for the herbal combination, compared with placebo, with respect to the reduction of other gastrointestinal symptoms. The combination preparation was found to be excellently tolerated. There was a total of 7 adverse events (test preparation: 4, placebo: 3), with a causal association with the treatment being ascribed in one case for the test preparation group and one case for the placebo group.

Adult↗

Antifungal activity of peppermint and sweet basil essential oils and their major aroma constituents on some plant pathogenic fungi from the vapor phase.

The vapors of peppermint oil and two of its major constituents (menthol and menthone), and sweet basil oil and two of its major constituents (linalool and eugenol), were tested against Sclerotinia sclerotiorum (Lib.), Rhizopus stolonifer (Ehrenb. exFr.) Vuill and Mucor sp. (Fisher) in a closed system. These fungi cause deterioration and heavy decay of peach fruit during marketing, shipping and storage. The essential oils, their major individual aroma constituents and blends of the major individual constituents at different ratios inhibited the growth of the fungi in a dose-dependent manner. Menthol was found to be the individual aroma constituent responsible for the antifungal properties of peppermint essential oil, while menthone alone did not show any effect at all doses. In the case of basil oil, linalool alone showed a moderate antifungal activity while eugenol showed no activity at all. Mixing the two components in a ratio similar to their concentrations in the original oil was found to enhance the antifungal properties of basil oil indicating a synergistic effect.

Acyclic Monoterpenes↗

Effects of intraduodenal application of peppermint oil (WS(R) 1340) and caraway oil (WS(R) 1520) on gastroduodenal motility in healthy volunteers.

Enteric-coated preparations containing a fixed peppermint oil/caraway oil combination (e.g. Enteroplant(R)) are widely used in patients with functional dyspepsia. The effect of a separate intraduodenal application of the active ingredients of Enteroplant(R) (90 mg peppermint oil (WS(R) 1340), 50 mg caraway oil (WS(R) 1520) per capsule) and of a hydrophobic phase galenic auxiliary material contained in the Enteroplant(R) formulation (dose as contained per capsule) on gastroduodenal motility were studied with stationary manometry in healthy volunteers. The carrier demanded by the experimental setup also served as a control. The results showed that: (1) during phase III of the migrating motor complex (MMC) the frequency and duration of contractions showed a significant decrease in the duodenum for WS(R) 1340; (2) WS(R) 1520 significantly reduced the contraction amplitudes in the duodenum during phase I and II of the MMC; (3) trends for decreased values were seen for WS(R) 1340 in the gastric corpus and duodenum and for WS(R) 1520 in the gastric antrum; (4) in the gastric corpus the duration of contractions was significantly reduced after application of WS(R) 1340 during phases I and II of the MMC; (5) WS(R) 1520 significantly reduced the contraction amplitudes and the duration of contractions in the gastric corpus during phase III of the MMC; (6) for the hydrophobic phase a moderate but significant decrease of duration of contractions in the duodenum and of frequency of contractions in the gastric corpus was seen. No adverse events were observed during the study. In conclusion, it could be shown that both WS(R) 1340 and WS(R) 1520 contribute to the efficacy of Enteroplant(R). They act locally in the stomach and duodenum to produce smooth-muscle relaxation. The effects of the active ingredients WS(R) 1340 and WS(R) 1520 substantially exceed the effects observed with the galenic auxiliary material and the carrier, respectively.

Adult↗

Isoprenoid biosynthesis via a mevalonate-independent pathway in plants: cloning and heterologous expression of 1-deoxy-D-xylulose-5-phosphate reductoisomerase from peppermint.

Two distinct pathways are utilized by plants for the biosynthesis of isopentenyl diphosphate, the universal precursor of isoprenoids. The classical acetate/mevalonate pathway operates in the cytosol, whereas plastidial isoprenoids originate via a novel mevalonate-independent route that involves a transketolase-catalyzed condensation of pyruvate and D-glyceraldehyde-3-phosphate to yield 1-deoxy-D-xylulose-5-phosphate as the first intermediate. Based on in vivo feeding experiments, rearrangement and reduction of deoxyxylulose phosphate have been proposed to give rise to 2-C-methyl-D-erythritol-4-phosphate as the second intermediate of this pyruvate/glyceraldehyde-3-phosphate pathway (1-3). The cloning of an Escherichia coli gene encoding an enzyme capable of converting 1-deoxy-D-xylulose-5-phosphate to 2-C-erythritol-4-phosphate was recently reported (4). A cloning strategy was developed for isolating the gene encoding a plant homolog of this enzyme from peppermint (Mentha x piperita), and the identity of the resulting cDNA was confirmed by heterologous expression in E. coli. Unlike the microbial reductoisomerase, the plant ortholog encodes a preprotein bearing an N-terminal plastidial transit peptide that directs the enzyme to plastids where the mevalonate-independent pathway operates in plants. The peppermint gene comprises an open reading frame of 1425 nucleotides which, when the plastidial targeting sequence is excluded, encodes a deduced enzyme of approximately 400 amino acid residues with a mature size of about 43.5 kDa.

Aldose-Ketose Isomerases↗

Metabolism of monoterpenes: oxidation of isopiperitenol to isopiperitenone, and subsequent isomerization to piperitenone by soluble enzyme preparations from peppermint (Mentha piperita) leaves.

Soluble enzyme extracts from peppermint leaves, when treated with polystyrene resin to remove endogenous monoterpenes and assayed with unlabeled substrates coupled with capillary gas-liquid chromatographic/mass spectrometric detection methods, were shown to oxidize isopiperitenol to isopiperitenone, and to isomerize isopiperitenone to piperitenone. The enzymes responsible for the monoterpenol dehydrogenation and the subsequent allylic isomerization were separated and partially purified by chromatography on Sephadex G-150, and were shown to have molecular weights of approximately 66,000 and 54,000, respectively. The general properties of the NAD-dependent dehydrogenase were examined, and specificity studies indicated that a double bond adjacent to the carbinol carbon was a required structural feature of the monoterpenol substrate. General properties of the isomerase were also determined, and it was demonstrated that the double bond migration catalyzed by this enzyme involved an intramolecular 1,3-hydrogen transfer. These enzymatic transformations represent two key steps in the metabolic pathway for the conversion of the initially formed cyclic olefin, (+/-)-limonene, to (-)-menthol and related monoterpenes characteristic of peppermint. Some stereochemical features of these reactions, and of the overall biogenetic scheme, are described.

Alcohol Oxidoreductases↗

Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea.

To determine whether aromatherapy can reduce postoperative nausea, the investigators studied 33 ambulatory surgery patients who complained of nausea in the PACU. After indicating the severity of nausea on a 100-mm visual analogue scale (VAS), subjects received randomized aromatherapy with isopropyl alcohol, oil of peppermint, or saline (placebo). The vapors were inhaled deeply through the nose from scented gauze pads held directly beneath the patients' nostrils and exhaled slowly through the mouth. Two and 5 minutes later, the subjects rated their nausea on the VAS. Overall nausea scores decreased from 60.6 +/- 4.3 mm (mean +/- SE) before aromatherapy to 43.1 +/- 4.9 mm 2 minutes after aromatherapy (P <.005), and to 28.0 +/- 4.6 mm 5 minutes after aromatherapy (P < 10(-6)). Nausea scores did not differ between the treatments at any time. Only 52% of the patients required conventional intravenous (IV) antiemetic therapy during their PACU stay. Overall satisfaction with postoperative nausea management was 86.9 +/- 4.1 mm and was independent of the treatment group. Aromatherapy effectively reduced the perceived severity of postoperative nausea. The fact that a saline "placebo" was as effective as alcohol or peppermint suggests that the beneficial effect may be related more to controlled breathing patterns than to the actual aroma inhaled.

2-Propanol↗

Cosuppression of limonene-3-hydroxylase in peppermint promotes accumulation of limonene in the essential oil.

cDNA clones encoding limonene synthase and limonene-3-hydroxylase, both driven by the CaMV 35S promoter, were independently transformed into peppermint (Menthaxpiperita) to alter the production and disposition of (-)-limonene, the first committed intermediate of essential oil biosynthesis in this species. Although both genes were constitutively expressed in leaves of transformed plants, the corresponding enzyme activities were not significantly increased in the glandular trichome sites of essential oil biosynthesis; thus, there was no effect on oil yield or composition in the regenerated plants. Cosuppression of the hydroxylase gene, however, resulted in the accumulation of limonene (up to 80% of the essential oil compared to about 2% of the oil in wild type plants), without influence on oil yield. These results indicate that limonene does not impose negative feedback on the synthase, or apparently influence other enzymes of monoterpene biosynthesis in peppermint, and suggests that pathway engineering can be employed to significantly alter essential oil composition without adverse metabolic consequences.

Cyclohexenes↗

Monoterpene double-bond reductases of the (-)-menthol biosynthetic pathway: isolation and characterization of cDNAs encoding (-)-isopiperitenone reductase and (+)-pulegone reductase of peppermint.

Random sequencing of a peppermint essential oil gland secretory cell cDNA library revealed a large number of clones that specified redox-type enzymes. Full-length acquisitions of each type were screened by functional expression in Escherichia coli using a newly developed in situ assay. cDNA clones encoding the monoterpene double-bond reductases (-)-isopiperitenone reductase and (+)-pulegone reductase were isolated, representing two central steps in the biosynthesis of (-)-menthol, the principal component of peppermint essential oil, and the first reductase genes of terpenoid metabolism to be described. The (-)-isopiperitenone reductase cDNA has an open reading frame of 942 nucleotides that encodes a 314 residue protein with a calculated molecular weight of 34,409. The recombinant reductase has an optimum pH of 5.5, and K(m) values of 1.0 and 2.2 microM for (-)-isopiperitenone and NADPH, respectively, with k(cat) of 1.3s(-1) for the formation of the product (+)-cis-isopulegone. The (+)-pulegone reductase cDNA has an open reading frame of 1026 nucleotides and encodes a 342 residue protein with a calculated molecular weight of 37,914. This recombinant reductase catalyzes the reduction of the 4(8)-double bond of (+)-pulegone to produce both (-)-menthone and (+)-isomenthone in a 55:45 ratio, has an optimum pH of 5.0, and K(m) values of 2.3 and 6.9 microM for (+)-pulegone and NADPH, respectively, with k(cat) of 1.8s(-1). Deduced sequence comparison revealed that these two highly substrate specific double-bond reductases show less than 12% identity. (-)-Isopiperitenone reductase is a member of the short-chain dehydrogenase/reductase superfamily and (+)-pulegone reductase is a member of the medium-chain dehydrogenase/reductase superfamily, implying very different evolutionary origins in spite of the similarity in substrates utilized and reactions catalyzed.

Amino Acid Sequence↗

Monoterpene composition of essential oil from peppermint (Mentha x piperita L.) with regard to leaf position using solid-phase microextraction and gas chromatography/mass spectrometry analysis.

Monoterpene compounds of leaf pairs and flowers of Mentha x piperita have been studied by direct headspace sampling using solid-phase microextraction coupled with gas chromatography/mass spectrometry (SPME-GC/MS). The content of peppermint-characteristic compounds such as menthol, menthyl acetate, and neomenthol increased in a basipetal direction (older plant parts), whereas menthone and isomenthone showed higher levels in the acropetal direction (younger plant parts). Higher levels of menthofuran were found in peppermint flowers in contrast to the leaves. SPME sampling resulted in relatively higher amounts of high-volatile monoterpenes and lower detection of less volatile compounds such as menthol and menthone, compared to solvent-based samples from essential oil distillation.

Gas Chromatography-Mass Spectrometry↗

Efficacy and tolerability of a fixed combination of peppermint oil and caraway oil in patients suffering from functional dyspepsia.

AIM: To assess the efficacy and safety of enteric coated capsules containing a fixed combination of 90 mg peppermint oil and 50 mg caraway oil (PCC; Enteroplant) in patients with functional dyspepsia. METHODS: A total of 96 out-patients received one capsule twice daily of PCC or placebo for 28 days. Primary efficacy variables were the intra-individual change in (i) pain intensity and (ii) sensation of pressure, heaviness and fullness between days 1 and 29, and the investigators' rating of (iii) global improvement (Clinical Global Impressions [CGI] item 2) on day 29. A global type I error of alpha=0.05 was controlled by a priori ordering of hypotheses. RESULTS: All patients were evaluable for efficacy and safety. On day 29, the average intensity of pain was reduced by 40% vs. baseline in the PCC group and by 22% in the placebo group. With regards to pressure, heaviness and fullness, a 43% reduction was observed for PCC vs. 22% for placebo. In CGI item 2, 67% (PCC) vs. 21% (placebo) of the patients were described as much or very much improved. In all three target parameters, the superiority of PCC over placebo was statistically significant. Six patients (PCC: 5; placebo: 1) reported adverse events, either unrelated to the trial, or attributable to an aggravation of the disease under investigation. Eructation with peppermint taste did not occur. CONCLUSION: These results demonstrate the good tolerability and the favourable risk-benefit ratio of PCC for the treatment of functional dyspepsia.

Adult↗

Limonene synthase, the enzyme responsible for monoterpene biosynthesis in peppermint, is localized to leucoplasts of oil gland secretory cells

Circumstantial evidence based on ultrastructural correlation, specific labeling, and subcellular fractionation studies indicates that at least the early steps of monoterpene biosynthesis occur in plastids. (4S)-Limonene synthase, which is responsible for the first dedicated step of monoterpene biosynthesis in mint species, appears to be translated as a preprotein bearing a long plastidial transit peptide. Immunogold labeling using polyclonal antibodies raised to the native enzyme demonstrated the specific localization of limonene synthase to the leucoplasts of peppermint (Mentha x piperita) oil gland secretory cells during the period of essential oil production. Labeling was shown to be absent from all other plastid types examined, including the basal and stalk cell plastids of the secretory phase glandular trichomes. Furthermore, in vitro translation of the preprotein and import experiments with isolated pea chloroplasts were consistent in demonstrating import of the nascent protein to the plastid stroma and proteolytic processing to the mature enzyme at this site. These experiments confirm that the leucoplastidome of the oil gland secretory cells is the exclusive location of limonene synthase, and almost certainly the preceding steps of monoterpene biosynthesis, in peppermint leaves. However, succeeding steps of monoterpene metabolism in mint appear to occur outside the leucoplasts of oil gland cells.

Journal Article↗

Metabolism of Monoterpenes: Acetylation of (-)-Menthol by a Soluble Enzyme Preparation from Peppermint (Mentha piperita) Leaves.

The essential oil from mature leaves of flowering peppermint (Mentha piperita L.) contains up to 15% (-)-menthyl acetate, and leaf discs converted exogenous (-)-[G-(3)H]menthol into this ester in approximately 15% yield of the incorporated precursor. Leaf extracts catalyzed the acetyl coenzyme A-dependent acetylation of (-)-[G-(3)H]menthol and the product of this transacetylase reaction was identified by radiochromatographic techniques. Transacetylase activity was located mainly in the 100,000g supernatant fraction, and the preparation was partially purified by combination of Sephadex G-100 gel filtration and chromatography on O-diethylaminoethyl-cellulose. The transacetylase had a molecular weight of about 37,000 as judged by Sephadex G-150 gel filtration, and a pH optimum near 9. The apparent K(m) and velocity for (-)-menthol were 0.3 mm and 16 nmol/hr. mg of protein, respectively. The saturation curve for acetyl coenzyme A was sigmoidal, showing apparent saturation near 0.1 mm. Dithioerythritol was required for maximum activity and stability of the enzyme, and the enzyme was inhibited by thiol directed reagents such as p-hydroxymercuribenzoate. Diisopropylfluorophosphate also inhibited transacylation suggesting the involvement of a serine residue in catalysis. The transacylase was highly specific for acetyl coenzyme A; propionyl coenzyme A and butyryl coenzyme A were not nearly as efficient as acyl donors (11% and 2%, respectively). However, the enzyme was much less selective with regard to the alcohol substrate, suggesting that the nature of the acetate ester synthesized in mint is more dependent on the type of alcohol available than on the specificity of the transacetylase. This is the first report on an enzyme involved in monoterpenol acetylation in plants. A very similar enzyme, catalyzing this key reaction in the metabolism of menthol, was also isolated from the flowers of peppermint.

Journal Article↗

Demonstration of the Intercellular Compartmentation of l-Menthone Metabolism in Peppermint (Mentha piperita) Leaves.

The metabolism of l-menthone, which is synthesized in the epidermal oil glands of peppermint (Mentha piperita L. cv. Black Mitcham) leaves, is compartmented; on leaf maturity, this ketone is converted to l-menthol and l-menthyl acetate in one compartment, and to d-neomenthol and d-neomenthyl glucoside in a separate compartment. All of the enzymes involved in these reactions are soluble when prepared from whole-leaf homogenates. Mechanical separation of epidermal fragments from the mesophyll, followed by preparation of the soluble enzyme fraction from each tissue, revealed that the neomenthol dehydrogenase and the glucosyl transferase resided specifically in the mesophyll layer, whereas the menthol dehydrogenase and substantial amounts of the acetyl transferase were located in the epidermis, presumably within the epidermal oil glands. These results suggest that the compartmentation of menthone metabolism in peppermint leaves is intercellular, not intracellular.

Journal Article↗

Delayed release peppermint oil capsules (Colpermin) for the spastic colon syndrome: a pharmacokinetic study.

Excretion of menthol (as glucuronide) from orally ingested peppermint oil contained in Colpermin was compared with oil contained in two soft gelatine capsules. Total 24 h urinary excretion of menthol was similar in the two formulations in healthy volunteers, but peak menthol excretion levels were lower and excretion delayed with Colpermin. Menthol excretion was reduced in ileostomy patients who took Colpermin and moderate amounts of unmetabolised menthol were recovered from the ileostomy effluent. This is consistent with Colpermin being a delayed-release form of peppermint oil.

Adolescent↗

Allergic and pseudo-allergic reactions caused by penicillins, cocoa and peppermint additives in penicillin factory workers examined by basophil histamine release.

Allergic and pseudo-allergic reactions were examined in penicillin factory workers exposed to the dust of preparations of pivampicillin and pivmecillinam. Among 14 workers basophils from five persons showed histamine release by challenge with penicillins, whereas no release was observed in controls of non-atopic individuals not working with the manufacturing of penicillin. Positive skin response was obtained in four workers by path testing and in three persons by scratch test revealing late but no immediate response. All the eight workers who were also exposed to flavour additives used in the penicillin preparations showed histamine release by cocoa and peppermint. The release was not changed by removal of immunoglobulins from the basophil cell surface and the additives caused a similar release in the controls. The histamine release caused by cocoa and peppermint therefore depend on non-immunological mechanisms, i.e. pseudo-allergic reactions which might contribute to the symptoms in penicillin factory workers.

Allergens↗

Effects of peppermint (Mentha piperita L.) extracts on experimental allergic rhinitis in rats.

The present study was carried out to clarify the effects of extracts of the leaves of Mentha piperita L. on experimental allergic rhinitis. The 50% EtOH extract of peppermint inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. The effect was dose-dependent and significant inhibition was observed at a concentration of 3 microg/ml. In addition, the 50% EtOH eluate separated from the 50% EtOH extract of peppermint by column chromatography (DIAION HP-20) was also effective in inhibiting histamine release at a concentration of 1 microg/ml. Nasal symptoms, sneezing and nasal rubbing induced by antigen challenge in actively sensitized rats were inhibited by oral administration of the 50% EtOH eluate. Significant inhibition of sneezing and nasal rubbing was observed at doses of 300 and 1000 mg/kg, p.o., respectively. Furthermore, the 50% EtOH eluate inhibited dye leakage into the nasal cavity of rats induced by antigen in a dose-dependent manner. These results suggested that extracts of Mentha piperita L. may be clinically effective in alleviating the nasal symptoms of allergic rhinitis.

Animals↗