Evaluation of the mechanism of action of paracetamol, drotaverine, and peppermint oil and their effects in combination with hyoscine butylbromide on colonic motility: human ex-vivo study.

Introduction: Drotaverine, paracetamol, and peppermint oil are often prescribed for the treatment of gastrointestinal spasm and pain. This study aimed to evaluate the effect of these drugs alone and combined with the well-known antispasmodic hyoscine butylbromide on the human colon. Methods: Colon samples were obtained from macroscopically normal regions of 68 patients undergoing surgery and studied in muscle bath. Drotaverine, paracetamol, and peppermint oil were tested alone and in combination with hyoscine butylbromide on (1) spontaneous contractility induced by isometric stretch (in the presence of 1 µM tetrodotoxin) and (2) contractility induced by 10-5 M carbachol and after (3) electrical field stimulation-induced selective stimulation of excitatory (in the presence of 1 mM Nω-nitro-L-arginine and 10 µM MRS2179) and (4) inhibitory (under non-adrenergic, non-cholinergic conditions) pathways. (5) Drotaverine alone was also tested on cAMP-dependent pathway activated by forskolin. Results: Compared with the vehicle, drotaverine and paracetamol (10-9-10-5 M) did not modify spontaneous contractions, carbachol-induced contractions, and responses attributed to selective activation of excitatory pathways. The addition of hyoscine butylbromide (10-7-10-5 M), concentration-dependently reduced myogenic contractions and carbachol- and electrical field stimulation-induced contractile responses. The association of paracetamol (10-4 M) and hyoscine butylbromide (10-7-10-5 M) was not different from hyoscine butylbromide alone (10-7-10-5 M). At higher concentrations (10-3M-3*10-3 M), paracetamol decreased myogenic and carbachol-induced contractions. The adenylate cyclase activator, forskolin, concentration-dependently reduced contractility, leading to smooth muscle relaxation. The effect of forskolin 10-7 M was concentration-dependently enhanced by drotaverine (10-6M-10-5M). Discussion: Peppermint oil reduced myogenic activity and carbachol- and electrical field stimulation-induced contractions. The association of hyoscine butylbromide and peppermint oil was synergistic since the interaction index measured with the isobologram was lower than 1. No effect was seen on the neural-mediated inhibitory responses with any of the drugs studied although peppermint oil reduced the subsequent off-contraction. Drotaverine and hyoscine butylbromide have a complementary effect on human colon motility as one stimulates the cAMP inhibitory pathway and the other inhibits the excitatory pathway. Peppermint oil is synergic with hyoscine butylbromide suggesting that a combination therapy may be more effective in treating patients. In contrast, at therapeutic concentrations, paracetamol does not modify colonic contractility, suggesting that the association of paracetamol and hyoscine butylbromide has independent analgesic and antispasmodic properties.

The combination of L-menthol and caraway oil does not affect gastric function but increases hunger in healthy subjects.

BACKGROUND: The heterogeneous character of functional gastrointestinal disorders, recently renamed into disorders of gut-brain interaction, makes finding effective treatment options challenging. Compared to synthetic drugs, phytotherapy can have broader pharmacological effects and is often better tolerated. This study aimed to investigate the effect of peppermint oil and caraway oil (POCO) on gastric function and symptom levels in 32 healthy subjects in a single-blinded, placebo-controlled, randomized, parallel design. METHODS: Gastric emptying rate was assessed using a 13C-breath test. Intragastric pressure was measured using high-resolution manometry in fasted state and during intragastric infusion of a nutrient drink (350 mL or until full satiation). GI symptoms were rated on a 100 mm VAS. Data were analyzed using linear mixed models. KEY RESULTS: POCO had no effect on intragastric pressure in fasted or fed state (p > 0.08 for all). No significant differences in gastric emptying rate were observed (p = 0.54). In the fasted state, a stronger increase in hunger and decrease in satiety were observed following POCO (p = 0.016 and p = 0.008, respectively). No differences in hunger and satiety were observed in the fed state (p > 0.31 for all). POCO induced less epigastric burning, bloating, and fullness (p < 0.05 for all). CONCLUSIONS: Acute POCO administration did not affect gastric function in healthy subjects, but increased fasted hunger ratings. The effects of POCO on gastric function and hunger sensations in patients with disorders of gut-brain interaction, and the contribution to symptom improvement, needs to be elucidated in future studies.

Asociación Española de Neurogastroenterología y Motilidad (ASENEM) updated review on the management of functional abdominal pain. / Documento de puesta al día de la Asociación Española de Neurogastroenterología y Motilidad (ASENEM) sobre el manejo del dolor abdominal funcional.

Functional abdominal pain is a disorder in which central and peripheral sensitization processes converge, leading to hypersensitivity and allodynia. Differential diagnosis is made with organic digestive, renal, gynecological, endocrine, or neurological diseases. Treatment should be individualized for each patient. In cases of debilitating pain, therapy combining drugs with different mechanisms of action can be initiated, while in less severe cases, therapy with a progressive introduction of drugs based on clinical response is advised. The first line includes general lifestyle advice and antispasmodic substances, like peppermint oil, anticholinergic/antimuscarinic, and calcium channels antagonists. In the second line of treatment, neuromodulating agents are added. Finally, when these measures fail, third-line treatments such as gabapentine and atypical antipsychotics are considered. Psychological interventions should be considered if specialized therapists are available to manage these disorders.

Modulating peppermint oil flavor release properties of emulsion-filled protein gels: Impact of cross-linking method and matrix composition.

For some food applications, it is desirable to control the flavor release profiles of volatile flavor compounds. In this study, the effects of crosslinking method and protein composition on the flavor release properties of emulsion-filled protein hydrogels were explored, using peppermint essential oil as a model volatile compound. Emulsion-filled protein gels with different properties were prepared using different crosslinking methods and gelatin concentrations. Flavor release from the emulsion gels was then monitored using an electronic nose, gas chromatography-mass spectrometry (GC-MS), and sensory evaluation. Enzyme-crosslinked gels had greater hardness and storage modulus than heat-crosslinked ones. The hardness and storage modulus of the gels increased with increasing gelatin concentration. For similar gel compositions, flavor release and sensory perception were faster from the heat-crosslinked gels than the enzyme-crosslinked ones. For the same crosslinking method, flavor release and perception decreased with increasing gelatin concentration, which was attributed to retardation of flavor diffusion through the hydrogel matrix. Overall, this study shows that the release of hydrophobic aromatic substances can be modulated by controlling the composition and crosslinking of protein hydrogels, which may be useful for certain food applications.

A comparative evaluation of peppermint oil and lignocaine spray as topical anesthetic agents prior to local anesthesia in children: a randomized clinical trial.

Background: In pediatric dentistry, fear and anxiety are common among children. Local anesthetics (LA) are widely used to control pain and reduce discomfort in children during dental treatment. Topical anesthetics play a vital role in reducing pain and the unpleasant sensation of a needle puncture in children. Peppermint oil has been extensively used for various diseases. However, its anesthetic properties remain unknown. Peppermint oil, used in mouthwashes, toothpastes, and other topical preparations has analgesic, anesthetic, and antiseptic properties. This study aimed to compare and evaluate pain perception following the topical application of peppermint oil versus lignocaine spray before an intraoral injection in children, aged 8-13 years. Method: Fifty-two children, aged between 8-13 years, who required local anesthesia for dental treatment were divided into two groups of 26 each by simple random sampling (Group 1: 0.2% peppermint oil and Group 2: lignocaine spray). In both groups, physiological measurements (e.g., heart rate) were recorded using pulse oximetry before, during, and after the procedure. Objective pain measurement (Sound Eye Motor (SEM) scale) during administration and subjective measuremeant (Wong-Baker Faces Pain Rating Scale (WBFPRS)) after LA administration were recorded. This was followed by the required treatment of the child.Physiological parameters were compared between the two groups using an independent t-test for intergroup assessment and a paired t-test and repeated-measures ANOVA for intragroup comparisons. The Mann-Whitney U test was used to analyze the pain scores. Results: Intragroup mean heart rates, before, during, and after treatment were statistically significantly different (P < 0.05). However, the intergroup mean pulse rates did not differ significantly between the two groups. The mean WBFPS score in the lignocaine spray group was 4.133 ± 2.06 was statistically different from that of the peppermint oil group (0.933 ± 1.03; P < 0.001*). The mean SEM score was significantly lower in the peppermint oil group than that in the lignocaine spray group (P = 0.006). No negative effects were observed in this study. Conclusion: 0.2% peppermint oil was effective in reducing pain perception.

Efficacy and safety of peppermint oil for the treatment in Japanese patients with irritable bowel syndrome: a prospective, open-label, and single-arm study.

BACKGROUND: In Europe, an herbal medicine containing peppermint oil is widely used in patients with irritable bowel syndrome (IBS). In Japan, however, no clinical evidence for peppermint oil in IBS has been established, and it has not been approved as a drug for IBS. Accordingly, we conducted a clinical study to confirm the efficacy and safety of peppermint oil (ZO-Y60) in Japanese patients with IBS. METHODS: The study was a multi-center, open-label, single-arm, phase 3 trial in Japanese outpatients with IBS aged 17-60 years and diagnosed according to the Rome III criteria. The subjects were treated with an oral capsule of ZO-Y60 three times a day before meals, for four weeks. The efficacy of ZO-Y60 was evaluated using the patient's global assessment (PtGA), IBS symptom severity score, stool frequency score, stool form score, and physician's global assessment (PGA). The safety of ZO-Y60 was also assessed. RESULTS: Sixty-nine subjects were treated with ZO-Y60. During the four-week administration of ZO-Y60, the improvement rate of the PtGA was 71.6% (48/67) in week 2 and 85.1% (57/67) in week 4. It was also suggested that ZO-Y60 is effective against any type of IBS (IBS with constipation, IBS with diarrhea, and mixed/unsubtyped IBS). The improvement rate of the PGA was 73.1% (49/67) in week 2 and 85.1% (57/67) in week 4, also confirming the efficacy of ZO-Y60. Adverse events were observed in 14 subjects (20.3%), however, none of these adverse events were categorized as serious. CONCLUSION: The efficacy of treatment was confirmed, subjective symptoms were improved, as was observed in previous clinical studies of ZO-Y60 conducted outside of Japan. All adverse reactions were previously known and were non-serious. These findings suggest that peppermint oil may be effective in the Japanese population and that it has an acceptable safety profile. TRIAL REGISTRATION: JAPIC Clinical Trials Information number: JapicCTI-121727 https://jrct.niph.go.jp/en-latest-detail/jRCT1080221685 . Registration date: 2012-01-10.

Effects of inhalation of peppermint oil after lumbar discectomy surgery on pain and anxiety levels of patients: A randomized controlled study.

AIM: This study was conducted to analyze the effects of the inhalation of peppermint oil after lumbar discectomy surgery on the pain and anxiety levels of patients. MATERIALS AND METHOD: This study was performed as a randomized controlled trial from September 2022 to June 2023 with 68 patients (34 patients in the experimental group and 34 patients in the control group). A Patient Information Form, the Numerical Pain Rating Scale, and the State Anxiety Inventory were used in the data collection process. The researcher administered the Patient Information Form to the patients before they underwent surgery. The State Anxiety Inventory and the Numerical Pain Rating Scale were administered to the patients after the second hour in the postoperative period. Next, for 10 minutes, only the patients in the experimental group inhaled five drops of peppermint oil dripped on a sterile gauze pad whereas no intervention was administered to the patients in the control group. Then, the State Anxiety Inventory and the Numerical Pain Rating Scale were administered again to the patients in both groups successively after the third and fourth hours in the postoperative period. RESULTS: After the second hour in the postoperative period, the difference between the mean pain or state anxiety levels of the two groups were not statistically significant (p > 0.05). On the other hand, after the third and fourth hours in the postoperative period, the differences between the two groups were statistically significant (p < 0.05). CONCLUSION: It was concluded that the inhalation of peppermint oil after lumbar discectomy surgery reduced pain and anxiety levels.

The Use of Fibers, Herbal Medicines and Spices in Children with Irritable Bowel Syndrome: A Narrative Review.

The pathophysiology of irritable bowel syndrome in children involves multiple factors. Thus, treatment options are variable, targeting both diet and the child's and parents' behavior via pharmacological and psychological interventions or neuromodulation. Parents are increasingly interested in complementary and alternative therapies for children with irritable bowel syndrome, especially when other treatments have been tried without relieving the child's symptoms. This paper examines current evidence for the benefits and side effects of herbal remedies and spices in pediatric patients with IBS. The benefits of peppermint oil, STW5, psyllium fiber, Curcuma, ginger, and other herbal medicines are discussed based on findings in the current literature.

Amended Safety Assessment of Mentha piperita (Peppermint)-Derived Ingredients as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of M piperita (peppermint)-derived ingredients. The Panel reviewed data relevant to the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing the same constituent(s) of concern, formulators are advised to be aware of these constituents and avoid reaching levels that may be hazardous to consumers. Industry should continue to use good manufacturing practices to limit impurities that could be present in botanical ingredients. The Panel concluded that M piperita (Peppermint) Oil, Extract, Leaf, and leaf-derived ingredients are safe in cosmetics in the present practices of use and concentration when formulated to be non-sensitizing, and that the available data are insufficient for determining that M piperita (Peppermint) Flower/Leaf/Stem Extract, M piperita (Peppermint) Flower/Leaf/Stem Water, and M piperita (Peppermint) Meristem Cell Culture are safe under the intended conditions of use in cosmetic formulations.

Development and Optimization of a Novel Lozenge Containing a Metronidazole-Peppermint Oil-Tranexamic Acid Self-Nanoemulsified Delivery System to Be Used after Dental Extraction: In Vitro Evaluation and In Vivo Appraisal.

In-depth studies on essential oil-based nanoemulsions (NEs) have centered on a variety of oral health issues. NEs improve the delivery of nonpolar active agents to sites and thereby boost the dissolution and distribution of the agents. Metronidazole-peppermint oil-tranexamic acid self-nanoemulsifying drug delivery systems (MZ-PO-TX-SNEDDS) were created and loaded into novel lozenges to act as antifungal, hemostatic, antimicrobial, and analgesic dosage forms after dental extractions. The design-of-experiments approach was used in creating them. To generate the NEs, different concentrations of MZ-PO (240, 180, and 120 mg), 2% TX (600, 450, and 300 mg), and Smix1:1 (600, 400, and 200 mg) were used. The ideal formulation had serum levels of 1530 U/mL of interleukin-6, a minimal inhibitory concentration against bacteria of 1.5 µg/mL, a droplet size of 96 nm, and a blood coagulation time of 16.5 min. Moreover, the produced NE offered better MZ release. The adopted design was used to produce the ideal formulation; it contained 240 mg of MZ-PO, 600 mg of 2% TX, and 600 mg of Smix1:1. It was incorporated into lozenges with acceptable characteristics and an improved capability for drug release. These lozenges had reasonable coagulation times, IL-6 serum levels, and MIC values. All of these characteristics are desirable for managing symptoms following tooth extractions. Therefore, these lozenges loaded with MZ-PO-TX-SNEDDs might be considered a beneficial paradigm for relieving complications encountered after tooth extractions.

Improved antioxidant activity and delivery of peppermint oil Pickering emulsion stabilized by resveratrol-grafted zein covalent conjugate/quaternary ammonium chitosan nanoparticles.

Novel nanoparticles (Z-R/H) were successfully fabricated by a resveratrol-grafted zein covalent conjugate (Z-R) combined with quaternary ammonium chitosan (HTCC), which were used as stabilizers to prepare peppermint oil (PO) Pickering emulsions with antioxidant activity. HTCC effectively adjusted wettability of Z-R conjugate, and three-phase contact angle of Z-R/H3:1 was moderate (95.01°). The influencing factors of Pickering emulsion formation, including volume fraction of PO, concentration of Z-R/H, and mass ratio of Z-R to HTCC, were evaluated by droplet size, ζ-potential, microscopic observation, and stability index analysis. Pickering emulsions stabilized by Z-R/H3:1 showed excellent physical stability under heat treatment. Z-R/H nanoparticles adsorbed on the oil-water interface yielded a dense filling layer as a physical barrier to improve the emulsion stability, which was validated by confocal laser-scanning microscopy. After 4 weeks of storage, retention rate of PO in Pickering emulsion stabilized by Z-R/H3:1 remained high (72.1 %). Electronic nose analysis showed that Z-R/H3:1-stabilized emulsion effectively prevented volatilization of PO aroma components. Additionally, PO and Z-R/H nanoparticles provided an additive antioxidant effect of Pickering emulsions against DPPH and ABTS free radicals. In summary, these novel Z-R/H nanoparticle offer promising applications as a stabilizer with great potential in preparing functional Pickering emulsions to improve essential oil delivery.

Comparison of in vitro and in vivo repellency bioassay methods for Ixodes scapularis nymphs.

BACKGROUND: Numerous bioassay methods have been used to test the efficacy of repellents for ticks, but the comparability of results across different methods has only been evaluated in a single study. Of particular interest are comparisons between bioassays that use artificial containers (in vitro) with those conducted on a human subject (in vivo) for efficacy testing of new potential unregistered active ingredients, which most commonly use in vitro methods. METHODS: We compared four different bioassay methods and evaluated three ingredients (DEET [N,N-Diethyl-meta-toluamide], peppermint oil and rosemary oil) and a negative control (ethanol) over a 6-h period. Two of the methods tested were in vivo bioassay methods in which the active ingredient was applied to human skin (finger and forearm bioassays), and the other two methods were in vitro methods using artificial containers (jar and petri dish bioassays). All four bioassays were conducted using Ixodes scapularis nymphs. We compared the results using nymphs from two different tick colonies that were derived from I. scapularis collected in the US states of Connecticut and Rhode Island (northern origin) and Oklahoma (southern origin), expecting that ticks of different origin would display differences in host-seeking behavior. RESULTS: The results between bioassay methods did not differ significantly, even when comparing those that provide the stimulus of human skin with those that do not. We also found that tick colony source can impact the outcome of repellency bioassays due to differences in movement speed; behavioral differences were incorporated into the assay screening. DEET effectively repelled nymphs for the full 6-h duration of the study. Peppermint oil showed a similar repellent efficacy to DEET during the first hour, but it decreased sharply afterwards. Rosemary oil did not effectively repel nymphs across any of the time points. CONCLUSIONS: The repellency results did not differ significantly between the four bioassay methods tested. The results also highlight the need to consider the geographic origin of ticks used in repellency bioassays in addition to species and life stage. Finally, our results indicate a limited repellent efficacy of the two essential oils tested, which highlights the need for further studies on the duration of repellency for similar botanically derived active ingredients and for evaluation of formulated products.

The effect of peppermint oil addition on the physical stability, irritability, and penetration of nanostructured lipid carrier coenzyme Q10.

Background: Coenzyme Q10 is formulated into Nanostructured Lipid Carrier (NLC) added with peppermint oil (PO) 0% (F1), 1% (F2), 1.5% (F3) and 2% (F4) to increase its penetration. Objective: This study aims to determine the effect of PO addition on the irritability, stability, and penetration of Coenzyme Q10 in the NLC. Methods: Coenzyme Q10 NLC was prepared using the High Shear Homogenization method. Furthermore, physical characterization was carried out. Physical stability testing was carried out for 90 days at a temperature of 25±5oC and an RH of 60±10%. The in vivo irritation test was observed for mice's back skin after 24 hours while the penetration study was further evaluated at 2 hours of the sample application. Results: Increasing the PO amount into Coenzyme Q10 NLC reduced the viscosity which was 329.1±15.5 cps for PO 0% to 219.9±2.9 cps for 2% addition. The observation of particle morphology showed that all NLC Coenzyme Q10 has a spherical particle shape with particle size between 188.25±13.22 to 197.80±14.19 nm. All formulas had high entrapment efficiency (>80%). PO addition did not cause changes in physical characteristics during 90 days of storage. The 24 hours' irritation test showed that F2 and F3 are non-irritating. By PO addition skin penetration improved at 2 hours' penetration study. Conclusion: PO addition up to 2% reduced viscosity, but did not affect particle size and morphology of Coenzyme Q10 NLC. Addition of PO up to 1.5% increased entrapment efficiency, did not irritate and increased the penetration of Coenzyme Q10 NLC.

Antibacterial and Antibiofilm Effects of Different Samples of Five Commercially Available Essential Oils.

Essential oils (EOs) have gained economic importance due to their biological activities, and increasing amounts are demanded everywhere. However, substantial differences between the same essential oil samples from different suppliers are reported-concerning their chemical composition and bioactivities-due to numerous companies involved in EOs production and the continuous development of online sales. The present study investigates the antibacterial and antibiofilm activities of two to four samples of five commercially available essential oils (Oregano, Eucalyptus, Rosemary, Clove, and Peppermint oils) produced by autochthonous companies. The manufacturers provided all EOs' chemical compositions determined through GC-MS. The EOs' bioactivities were investigated in vitro against Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). The antibacterial and antibiofilm effects (ABE% and, respectively, ABfE%) were evaluated spectrophotometrically at 562 and 570 nm using microplate cultivation techniques. The essential oils' calculated parameters were compared with those of three standard broad-spectrum antibiotics: Amoxicillin/Clavulanic acid, Gentamycin, and Streptomycin. The results showed that at the first dilution (D1 = 25 mg/mL), all EOs exhibited antibacterial and antibiofilm activity against all Gram-positive and Gram-negative bacteria tested, and MIC value > 25 mg/mL. Generally, both effects progressively decreased from D1 to D3. Only EOs with a considerable content of highly active metabolites revealed insignificant differences. E. coli showed the lowest susceptibility to all commercially available essential oils-15 EO samples had undetected antibacterial and antibiofilm effects at D2 and D3. Peppermint and Clove oils recorded the most significant differences regarding chemical composition and antibacterial/antibiofilm activities. All registered differences could be due to different places for harvesting the raw plant material, various technological processes through which these essential oils were obtained, the preservation conditions, and complex interactions between constituents.

Development and characterization of nanoemulsions loaded with essential oil and ß-cypermethrin and their bioefficacy on insect pest of economic and medical importance.

BACKGROUND: The development of novel and ecofriendly tools plays an important role in insect pest management. Nanoemulsions (NEs) based on essential oils (EOs) offer a safer alternative for human health and the environment. This study aimed to elaborate and evaluate the toxicological effects of NEs containing peppermint or palmarosa EOs combined with ß-cypermethrin (ß-CP) using ultrasound technique. RESULTS: The optimized ratio of active ingredients to surfactant was 1:2. The NEs containing peppermint EO combined with ß-CP (NEs peppermint/ß-CP) were polydisperse with two peaks at 12.77 nm (33.4% intensity) and 299.1 nm (66.6% intensity). However, the NEs containing palmarosa EO combined with ß-CP (NEs palmarosa/ß-CP) were monodisperse with a size of 104.5 nm. Both NEs were transparent and stable for 2 months. The insecticidal effect of NEs was evaluated against Tribolium castaneum and Sitophilus oryzae adults, as well as Culex pipiens pipiens larvae. On all these insects, NEs peppermint/ß-CP enhanced pyrethroid bioactivity from 4.22- to 16-folds while NEs palmarosa/ß-CP, from 3.90- to 10.6-folds. Moreover, both NEs maintained high insecticidal activities against all insects for 2 months, although a slight increase of the particle size was detected. CONCLUSION: The NEs elaborated in this work can be considered as highly promising formulations for the development of new insecticides. © 2023 Society of Chemical Industry.

Cinnamon Oil Encapsulated with Silica Nanoparticles: Chemical Characterization and Evaluation of Insecticidal Activity Against the Rice Moth, Corcyra cephalonica.

Cinnamon (Cinnamomum zeylanicum Blume) essential oil has vast potential as an antimicrobial but is limited by its volatility and rapid degradation. To decrease its volatility and prolong the efficacy of the biocide, cinnamon essential oil was encapsulated into mesoporous silica nanoparticles (MSNs). The characterization of MSNs and cinnamon oil encapsulated with silica nanoparticles (CESNs) was estimated. Additionally, their insecticidal activity against the rice moth Corcyra cephalonica (Stainton) larvae was evaluated. The MSN surface area decreased from 893.6 to 720 m2 g-1 and the pore volume also decreased from 0.824 to 0.7275 cc/g after loading with cinnamon oil. X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX), and N2 sorption by Brunauer-Emmett-Teller (BET) confirmed the successful formation and evolution of the synthesized MSNs and CESN structures. The surface characteristics of MSNs and CESNs were analyzed by scanning and transmission electron microscopy. Compared with the sub-lethal activity values, the order of toxicity after 6 days of exposure was MSNs ˃ CESN ˃ cinnamon oil ˃ silica gel ˃ peppermint oil. The efficacy of CESNs gradually increases its toxicity more than MSN after the 9th day of exposure.

The Use of Peppermint Oil in Gastroenterology.

BACKGROUND: For decades, mint has been used worldwide for its relieving effects against gastrointestinal disturbances. Peppermint is a perennial herb common in Europe and North America. The active ingredient of peppermint oil is menthol and has various gastroenterological and non-gastroenterological uses, especially in the context of functional gastrointestinal disorders (FGIDs). METHODS: We conducted a literature search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: peppermint oil, gastro-intestinal motility, irritable bowel syndrome, functional dyspepsia, gastrointestinal sensitivity and gastrointestinal endoscopy. RESULTS: Peppermint oil and its constituents exert smooth muscle relaxant and anti-spasmodic effects on the lower esophageal sphincter, stomach, duodenum, and large bowel. Moreover, peppermint oil can modulate visceral and central nervous system sensitivity. Taken together, these effects suggest using peppermint oil both for improved endoscopic performance and for treating functional dyspepsia and irritable bowel syndrome. Importantly, peppermint oil has an attractive safety profile compared to classical pharmacological treatments, especially in FGIDs. CONCLUSION: Peppermint oil is a safe herbal medicine therapy for application in gastroenterology, with promising scientific perspectives and rapidly expanding use in clinical practice.

Menthacarin, a Proprietary Peppermint Oil and Caraway Oil Combination, Improves Multiple Complaints in Patients with Functional Gastrointestinal Disorders: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review summarizes published data on Menthacarin, the proprietary combination of peppermint oil and caraway oil, in the treatment of functional gastrointestinal disorders. Efficacy was assessed by meta-analysis of placebo-controlled trials. METHODS: We searched PubMed, the Cochrane Library, and the manufacturer's information system for clinical studies investigating the safety and efficacy of Menthacarin. Efficacy analyses included change from baseline of epigastric pain and general improvement of the patients' condition. RESULTS: Five randomized trials involving 580 patients were found, demonstrating significant effects of Menthacarin on symptoms of functional dyspepsia (FD) compared to placebo or similar effects compared to a reference drug. Seven other studies reported favorable results on therapeutic application in FD patients with concomitant Helicobacter pylori infection, in irritable bowel syndrome (IBS), and on tolerability in FD patients from 12 years of age. Three trials in FD with 249 patients were eligible for meta-analysis. Results demonstrate a significant reduction in pain intensity (standardized mean difference: 0.80; 95% confidence interval (CI): 0.39-1.21) and in item 2 of the Clinical Global Impression Scale (risk ratio: 2.65; 95% CI: 1.81-3.87) for Menthacarin. CONCLUSIONS: Menthacarin was shown to be effective and safe for the treatment of FD and represents a promising option for symptoms of IBS.

Self-Medication for the Treatment of Abdominal Cramps and Pain-A Real-Life Comparison of Three Frequently Used Preparations.

Functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS), are frequently handled by self-management with over-the-counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol, and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptoms. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change in intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity, and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.

Systematic review and meta-analysis: efficacy of peppermint oil in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, with a complex pathophysiology. Antispasmodics are prescribed as first-line therapy because of their action on gut dysmotility. In this regard, peppermint oil also has antispasmodic properties. AIM: To update our previous meta-analysis to assess efficacy and safety of peppermint oil, particularly as recent studies have cast doubt on its role in the treatment of IBS METHODS: We searched the medical literature up to 2nd April 2022 to identify randomised controlled trials (RCTs) of peppermint oil in IBS. Efficacy and safety were judged using dichotomous assessments of effect on global IBS symptoms or abdominal pain, and occurrence of any adverse event or of gastro-oesophageal reflux. Data were pooled using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 10 eligible RCTs (1030 patients). Peppermint oil was more efficacious than placebo for global IBS symptoms (RR of not improving = 0.65; 95% CI 0.43-0.98, number needed to treat [NNT] = 4; 95% CI 2.5-71), and abdominal pain (RR of abdominal pain not improving = 0.76; 95% CI 0.62-0.93, NNT = 7; 95% CI 4-24). Adverse event rates were significantly higher with peppermint oil (RR of any adverse event = 1.57; 95% CI 1.04-2.37). CONCLUSIONS: Peppermint oil was superior to placebo for the treatment of IBS, but adverse events were more frequent, and quality of evidence was very low. Adequately powered RCTs of peppermint oil as first-line treatment for IBS are needed.