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Effects of intraduodenal application of peppermint oil (WS (R) 1340) and caraway oil (WS (R) 1520) on gastroduodenal motility in healthy volunteers
Phytotherapy Research
Abstract
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.
... and a lower incidence of adverse events (AEs) than the prokinetics group in treating FD. [15] However, this meta-analysis had a critical drawback: as RCTs were included in the meta-analysis regardless of blinding, none of the trials described allocation concealment Table 1 Complementary and alternative medicine used for patients with functional dyspepsia. Multicenter, double-blind study, [29] doubleblind RCTs, [30,31] Swiss meta-analysis, [32] retrospective cohort study [33] Iberogast (Bayer AG, Germany), developed in Germany in 1961 ...
... Other natural products A combination of peppermint oil and caraway oil Germany single-arm study, [29] animal study, [34] Chinese SR/meta-analysis [35] l-Menthol and caraway Germany RCT, [36] American RCT [37] FDgard, a commercially available medical food N sativa seed oil (black seed oil) ...
... Angelica gigas (Garden angelica root), Silybum marianum (Milk thistle fruits), Carum carvi (Caraway fruits), Chelidonium majus (Greater celandine), Iberis amara (Bitter candy tuft), Glycyrrhiza uralensis (Liquorice root), Chamaemelum nobile (Chamomile flowers), Mentha piperita (peppermint herb), and Melissa officinalis (balm leaf). [29] It was developed in Germany in 1961 and is available without prescription in Europe. It has been claimed to possess GI motility improvement, anti-inflammatory, antioxidative, and free radical-inhibiting properties, as well as reduced gastric acid secretion. ...
A considerable number of Asian patients with functional dyspepsia (FD) are searching for complementary and alternative medicine (CAM) because they are unsatisfied with conventional medical treatment. However, no article has focused on CAM for FD from Asian perspective. In Asian countries, many traditional herbal formulas, including Banha-sasim-tang, Soyo-san, Sihosogan-san, Yukgunja-tang, and Pyeongwi-san, are used in patients with FD. In the few blinded and placebo-controlled studies conducted, the weak evidence regarding the effectiveness of herbal prescriptions in patients with FD did not allow any conclusions to be made. The clinical efficacy and safety of STW-5 were proven in several prospective randomized controlled trials and systematic reviews. Hence, it was recently approved as a therapeutic option for the treatment of FD. Peppermint and caraway, FDgard, black seed oil, and Jollab have been used in patients with FD, but there is limited evidence supporting their use. Reviews of acupuncture in patients with FD showed inconsistent results: a Cochrane review reported a negative result, while other meta-analyses reported positive results. Psychotherapy, including hypnotherapy, psychoanalytic psychotherapy, and cognitive behavioral therapy, may be used in patients with FD, although it is only supported by weak evidence. Therefore, well-planned, large-scale studies are necessary to evaluate the efficacy of CAM in treating FD, especially in Asian countries.
... In clinical studies, phytotherapeutic combinations containing caraway oil exhibited beneficial effects on gastro-intestinal symptoms, such as dyspepsia and functional dyspeptic syndrome (Coon & Ernst, 2002;Freise & Kohler, 1999;Madisch et al., 1999Madisch et al., , 2004Mascher et al., 2001;May et al., 1996May et al., , 2000Micklefield et al., 2003). None of these studies clearly defined the effects of caraway on gastro-intestinal motor activities, as the clinical dyspeptic syndrome is a complex pathophysiological process in which alteration of motility, alteration of sensation as well as psychosocial factors are involved in the generation of dyspepsia (Camilleri, 2001). ...
... None of these studies clearly defined the effects of caraway on gastro-intestinal motor activities, as the clinical dyspeptic syndrome is a complex pathophysiological process in which alteration of motility, alteration of sensation as well as psychosocial factors are involved in the generation of dyspepsia (Camilleri, 2001). Caraway oil inhibited the motor activities of SMC of the gallbladder, stomach, trachea and ileum (Boskabady et al., 2003;Goerg & Spilker, 2003;Micklefield et al., 2003;Reiter & Brandt, 1985). Recently, in vitro and in vivo experiments demonstrated antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities for C. copticum seeds (Gilani et al., 2005). ...
... Recently, Gilani and his co-workers (2005) demonstrated that C. copticum extract has reduced spontaneous contractile activity and inhibited K + -induced contractions in intestinal preparation of rabbits. In clinical trials on healthy volunteers, inhibitory effects of caraway extract on the number of contractions and contraction amplitudes of the migrating motor complex and gall-bladder emptying have been observed (Goerg & Spilker, 2003;Micklefield et al., 2003). These reported findings may support the inhibitory effect of caraway extract on SMC found in the present study. ...
The present study investigates the direct effects of Carum carvi L. (Apiaceae) ethanol extract on dispersed intestinal smooth muscle cells (SMC) of guinea pigs. Effects of the plant extract on SMC and of acetylcholine (Ach) on extract pretreated SMC were measured by micrometric scanning technique. Three different extract concentrations (2.5 mg/mL, 250 mug/mL, and 25 mug/mL) were used. Ethanol extract of C. carvi reduced significantly the response of dispersed SMC to Ach. Pretreatment of SMC with the highest concentration of C. carvi ethanol extract (2.5 mg/mL) has significantly inhibited the response of SMC to Ach. The data obtained indicate a dose-dependent inhibition of the contraction induced by Ach. This response may explain, in part, the beneficial effect of caraway in relieving gastrointestinal symptoms associated with dyspepsia.
... Oral combination of caraway and peppermint oils or peppermint oil completely inhibited the gallbladder emptying [46] and gastric motility [60] in healthy volunteers, whereas caraway oil had no effect on orocecal transit time [46]. Caraway oil reduced the contraction amplitudes in the duodenum and gastric corpus with reduction in contractions duration of the gastric corpus during certain phases of the migrating motor complex [47]. Peppermint and caraway oils locally relaxed the smooth muscles [60], and this effect is related to the local action of both essential oils [47]. ...
... Caraway oil reduced the contraction amplitudes in the duodenum and gastric corpus with reduction in contractions duration of the gastric corpus during certain phases of the migrating motor complex [47]. Peppermint and caraway oils locally relaxed the smooth muscles [60], and this effect is related to the local action of both essential oils [47]. Peppermint and caraway oils inhibit the l-type calcium channels without any nerve-dependent activity [83]. ...
... Scientific evidence for the effects of caraway oil remains limited, with only one study in healthy subjects reporting attenuating effects on GI contractility. 18 The combination of both natural oils showed comparable therapeutic efficacy to the prokinetic agent cisapride in FD patients. 1,19 Moreover, in a placebocontrolled trial in FD, significant beneficial effects on symptoms already occurred on the first day of treatment. ...
... It was reported that acute intraduodenal administration of peppermint oil increased the frequency of duodenal phase III contractions and decreased the length of phase I and II. 18 The effect of the combination of peppermint oil and caraway oil on the upper digestive tract remains uninvestigated. Furthermore, the underlying mechanisms behind the motility changes are still unknown. ...
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.
... The remaining 37 records were screened for compliance with the inclusion criteria, resulting in 26 publications for which full text articles were assessed for eligibility. During full text screening, a further 12 articles had to be excluded [19,[23][24][25][26][27][28][29][30][31][32][33]. Five publications on clinical pharmacology or pharmacokinetic studies without a therapeutic approach were not taken into consideration [23][24][25][26][27]. ...
... During full text screening, a further 12 articles had to be excluded [19,[23][24][25][26][27][28][29][30][31][32][33]. Five publications on clinical pharmacology or pharmacokinetic studies without a therapeutic approach were not taken into consideration [23][24][25][26][27]. The title of one study published in Chinese contained one former brand name of Menthacarin ('Enteroplant') [19]. ...
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, 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 (SMD 0.80; 95% CI: 0.39-1.21) and in item 2 of the Clinical Global Impression Scale (RR 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.
... In addition, there is also evidence indicating that PMO decreases small bowel contractility and attenuates orocecal transit. Both duodenally instilled and given orally PMO decreased duodenal contractions in a double contrast barium study and manometry (37)(38)(39). Furthermore, a study using hydrogen breath testing showed that the PMO combination with caraway oil had delayed orocecal transit in healthy volunteers (40). ...
... Given orally or topically sprayed PMO also decreased spasm of the sto mach (37,47). Some studies using manometry and/or barostat have demonstrated various effects on the gastric physiology such as decreased intragastric pressure, decreased gastric motility index, with no change in gastric accommodation (38,39,48). However, studies addressing the effects of PMO on GE have shown mixed results (40,49). ...
The pathophysiology of functional gastrointestinal disorders (FGIDs) is still unclear and various complex mechanisms have been suggested to be involved. In many cases, improvement of symptoms and quality of life (QoL) in patients with FGIDs is difficult to achieve with the single-targeted treatments alone and clinical application of these treatments can be challenging owing to the side effects. Herbal preparations as complementary and alternative medicine can control multiple treatment targets of FGIDs simultaneously and relatively safely. To date, many herbal ingredients and combination preparations have been proposed across different countries and together with a variety of traditional medicine. Among the herbal therapies that are comparatively considered to have an evidence base are iberogast (STW-5) and peppermint oil, which have been mainly studied and used in Europe, and rikkunshito and motilitone (DA-9701), which are extracted from natural substances in traditional medicine, are the focus of this review. These herbal medications have multi-target pharmacology similar to the etiology of FGIDs, such as altered intestinal sensory and motor function, inflammation, neurohormonal abnormality, and have displayed comparable efficacy and safety in controlled trials. To achieve the treatment goal of refractory FGIDs, extensive and high quality studies on the pharmacological mechanisms and clinical effects of these herbal medications as well as efforts to develop new promising herbal compounds are required.
... For the management of FD, peppermint oil or L-menthol is used in combination with caraway oil. Pharmacodynamic studies have reported that a combination of peppermint oil and caraway oil (POCO) may have a prokinetic effect [10,11] and interact synergistically in attenuating postinflammatory visceral hyperalgesia [12], all of which might contribute to the therapeutic benefit for FD. ...
... POCO's beneficial effects in FD are likely related to its unique prokinetic, anti-inflammatory, gastroprotective, and spasmolytic [8] properties, which can be identified in modern pharmacological studies. In healthy volunteers, this combination has been shown to reduce the frequency and amplitude of contractions in the migrating motor complex (MMC) [11], relax the gall bladder, and slow small intestinal transit [22]. In dyspepsia patients, oral peppermint oil seemed to exert a significant spasmolytic effect in the esophagus, lower stomach, and duodenal bulb [23]. ...
A combination of peppermint oil and caraway oil (POCO) with its unique properties has been shown clinical benefits for FD. However, the potent statistical data to confirm its effects are lacking. This meta-analysis thus aimed at evaluating the efficacy and safety of POCO compared with placebo in treating patients with FD. We searched CENTRAL, PubMed, EMBASE (Ovid), Web of Science, Google Scholar, China National Knowledge Infrastructure database, Wanfang, and VIP databases for randomized clinical trials (RCTs) up to June 2019. Dichotomous data were shown as a risk ratio (RR) with 95% confidence intervals (CIs). All data were analyzed by Review Manager 5.2 software. The search identified 382 citations, and 5 RCTs (578 participants) were included. POCO showed a statistically significant effect in global improvement of FD symptoms (RR for not much or very much improvement 0.59, 95% CI: 0.49 to 0.71, P<0.00001 , I² 36%, NNT 3) and improvement in epigastric pain (RR 1.61, 95% CI: 1.28 to 2.03, P<0.0001 , I² 0%, NNT 3). There were no significant differences in the total number of adverse events between POCO and placebo (NNH 40). In conclusion, this is the first meta-analysis to assess the effects of POCO in FD. POCO is an effective and safe short-term treatment for FD. However, current findings are based on smaller sample sizes and low/very low quality of the evidence. More well-designed RCTs with large sample sizes of FD patients are required.
... Previous studies have shown that peppermint oil and caraway oil (primarily composed of approximately equal parts D-carvone and L-limonene), either alone or in combination, may possess gastroprotective (5-8), analgesic (9), prokinetic (10,11), and antiinflammatory (12,13) properties, all of which might benefit patients with FD. Peppermint oil and caraway oil have demonstrated synergistic peripheral analgesic activity in preclinical studies (14). ...
... This site was targeted primarily due to the mounting evidence that gastroduodenal mucosal integrity and low-grade inflammation play a role in FD (19). Furthermore, studies have shown that caraway oil and peppermint oil act on the duodenum to induce smooth muscle relaxation (11), and that L-menthol has anti-inflammatory effects (12). Since the combination of caraway oil and L-menthol is an oil, it has not been possible to deliver this combination reliably and quickly to the duodenum, with the historical oil in enteric-coated capsule formulations. ...
OBJECTIVES
We conducted a randomized, placebo-controlled trial, which evaluated a novel formulation of caraway oil and L-menthol using microsphere-based site-specific targeting (COLM-SST) vs placebo in patients with functional dyspepsia (FD).
METHODS
Adult men and women with FD defined by Rome III criteria were recruited. Patients were randomized to COLM-SST (25 mg of caraway oil and 20.75 mg of L-menthol per capsule, at 2 capsules per dose, twice per day) or placebo. Efficacy was measured at 24 hours, 2 weeks, and 4 weeks. Patients were allowed to take concomitant medications for their FD throughout the trial, and rescue medicines were allowed, 48 hours after start of dosing.
RESULTS
Ninety-five patients were enrolled (mean age = 43.4 years; 75.8% women). At 24 hours, the active arm reported a statistically significant reduction in postprandial distress syndrome symptoms (P = 0.039), and a nonsignificant trend toward benefit of epigastric pain syndrome symptoms (P = 0.074). In patients with more severe symptoms, approximately 3 quarters of patients showed substantial global improvement (i.e., clinical global impressions), after 4 weeks of treatment, vs half in the control arm. These differences were statistically significant for patients with epigastric pain syndrome (P = 0.046), and trending toward significance for patients with postprandial distress syndrome (P = 0.091). There was no statistically significant difference between groups for Global Overall Symptom scores for the overall population at 2 and 4 weeks. Treatment emergent adverse events were mild to moderate, and no serious adverse events were reported.
DISCUSSION
In patients taking their usual medications for FD, COLM-SST provided rapid relief (within 24 hours) and relief of severe FD symptoms. It was safe and well tolerated.
... The results showed that the intraduodenal application of the combined formula could reduce motility in the gastric corpus and antrum. However, the small number of volunteers, the combined formulation, and especially the short duration of the study performed in a day could bias the interpretation of the results [124]. ...
Background/Objectives: Gastrointestinal disorders include a broad spectrum of clinical conditions due to various symptoms. Abdominal pain claims attention as it can be associated with multiple diseases, and some of them can lead to chronic abdominal pain, such as chronic gastritis and irritable bowel syndrome. Moreover, dyspepsia is also a prevalent condition, and its symptoms are postprandial fullness, epigastric pain or burn, and early satiety. Conventional therapeutic approaches for gastrointestinal disorders exist, but the Mentha plant has a millenary tradition. Mentha aerial parts and leaves hold therapeutic and pharmacological value, and its components are characterized as non-essential oil with superabundant phenolic compounds, and essential oil classified as volatile secondary metabolites like menthol and menthone. Studies have shown that Mentha species can exert benefits by modulating the inflammatory process and scavenging free radicals, which can benefit gastrointestinal tract disorders. The aim of this review was to systematically investigate the effects of Mentha species on gastrointestinal disorders. Methods: Sixteen clinical trials included patients diagnosed with irritable bowel syndrome, functional dyspepsia, and functional abdominal pain, as well as some healthy volunteers. The COCHRANE tool was utilized to assess the bias of the included studies. Results: Most studies reported significant outcomes for Mentha oil-treated groups, such as better control of abdominal pain and discomfort, even though two trials did not report superior outcomes. Conclusions: Due to the increasing interest in natural compounds, further clinical trials are necessary to confirm the status of Mentha for improvement in gastrointestinal disorders.
... Studi farmakodinamik telah melaporkan bahwa kombinasi minyak daun mint dan minyak jintan (POCO) dapat memiliki efek prokinetik dan berinteraksi secara sinergis dalam melemahkan postinflamatory visceral hyperalgesia dimana efek ini dapat berkontribusi pada manfaat terapeutik untuk terapi dispesia fungsional. 18,19,20 Berdasarkan berbagai penelitian yang menunjukkan efikasi kombinasi minyak daun mint dan minyak jintan terhadap dispepsia fungsional maka, penulis bertujuan mengintegrasikan dan menyimpulkan hal-hal yang diketahui dalam area penelitian tersebut untuk dilakukan kajian pustaka untuk mendapatkan informasi secara komprehensif mengenai khasiat apa saja yang terkandung dalam minyak daun mint dan minyak jintan sebagai potensi obat herbal yang digunakan untuk mengobati pasien dispepsia fungsional. ...
Dispepsia fungsional mempengaruhi >20% populasi umum. Gejala-gejala dispepsia fungsional sering dikaitkan dengan gangguan kualitas hidup pasien. Sampai sekarang, pengobatan dispepsia fungsional masih kontrovesial. Oleh karena itu, perlu adanya review mengenai terapi alternatif lain yang salah satunya dapat berasal dari tanaman herbal. Hasil literature review menunjukkan terapi kombinasi minyak peppermint dan minyak jintan memiliki aktivitas sinergis karena minyak peppermint memiliki sifat spasmolitik dan minyak jintan berperan dalam peningkatan tonus otot polos sehingga efektif untuk menghilangkan rasa sakit dan rasa tidak nyaman pada pasien dengan dispepsia fungsional. Pengembangan penelitian lebih lanjut dengan skala yang lebih besar dan berjangka panjang diperlukan untuk mengevaluasi efektivitas dari terapi herbal ini.
... Studi farmakodinamik telah melaporkan bahwa kombinasi minyak daun mint dan minyak jintan (POCO) dapat memiliki efek prokinetik dan berinteraksi secara sinergis dalam melemahkan postinflamatory visceral hyperalgesia dimana efek ini dapat berkontribusi pada manfaat terapeutik untuk terapi dispesia fungsional. 18,19,20 Berdasarkan berbagai penelitian yang menunjukkan efikasi kombinasi minyak daun mint dan minyak jintan terhadap dispepsia fungsional maka, penulis bertujuan mengintegrasikan dan menyimpulkan hal-hal yang diketahui dalam area penelitian tersebut untuk dilakukan kajian pustaka untuk mendapatkan informasi secara komprehensif mengenai khasiat apa saja yang terkandung dalam minyak daun mint dan minyak jintan sebagai potensi obat herbal yang digunakan untuk mengobati pasien dispepsia fungsional. ...
ABSTRAK Pendahuluan: Dispepsia fungsional mempengaruhi lebih dari 20% populasi umum. Gejala-gejala dispepsia fungsional sering dikaitkan dengan gangguan kualitas hidup pasien. Hingga saat ini, pengobatan dispepsia fungsional masih kontroversial. Oleh karena itu, perlu adanya review mengenai terapi alternatif lain yang salah satunya dapat berasal dari tanaman herbal. Pembahasan: Hasil literature review menunjukkan terapi kombinasi minyak peppermint dan minyak jintan memiliki aktivitas sinergis karena minyak peppermint memiliki sifat spasmolitik dan minyak jintan berperan dalam peningkatan tonus otot polos sehingga efektif untuk menghilangkan rasa sakit dan rasa tidak nyaman pada pasien dengan dispepsia fungsional. Simpulan: Pengembangan penelitian lebih lanjut dengan skala yang lebih besar dan berjangka panjang diperlukan untuk mengevaluasi efektivitas dari terapi herbal ini. Kata Kunci: dispepsia fungsional, minyak daun mint, minyak jintan, pengobatan herbal Tinjauan Pustaka ABSTRACT Background: Functional dyspepsia affects> 20% of the general population. The symptoms of functional dyspepsia are often associated with impaired quality of life of the patient. Until now, the treatment of functional dyspepsia is still controversial. Therefore, there needs to be a review of other alternative therapies, such as traditional medicine. Methods: This paper uses a literature review method. The journals used in literature reviews are obtained through search engines such as Google Scholar, PubMed, and Science Direct. The journals used are in Indonesian and English. Discussion: The literature review shows that combination therapy of peppermint oil and caraway oil has synergistic activity because peppermint oil has spasmolytic properties and caraway oil plays a role in increasing smooth muscle tone so that it is effective in relieving pain and discomfort in patients with functional dyspepsia. Conclusion: Further research development with a larger scale and long term is needed to evaluate the effectiveness of this herbal therapy.
... In various basic science studies as well as in human pharmacological studies, a spasmolytic action on smooth muscle was demonstrated for peppermint oil due to its calcium-antagonistic properties, while caraway oil shows antimeteoric and choleretic effects and decreases the muscular tone [18,19,20,21,22,23]. Moreover, peppermint oil has shown choleretic [24] and direct analgesic properties through inhibition of voltage-gated sodium channels [25,26] and activation of the cold receptor TRPM8 [27]. ...
Background Menthacarin was shown to be effective and safe in clinical trials in patients with functional dyspepsia (FD). Long-term treatment results have not been reported yet.
Methods An open-label, 11-month follow-up (FU) was offered to FD patients who had undergone treatment with Menthacarin (1 gastro-resistant capsule b.i.d. vs. placebo (PL)) in a 4-week, double-blind, clinical trial. During FU, all patients (former verum and PL) were treated with 1 gastro-resistant capsule Menthacarin b.i.d. Main outcomes were the changes in pain intensity and severity of sensation of pressure, heaviness, and fullness from original baseline and global improvement.
Results 70 patients were included in the analyses (former Menthacarin group: 36, former PL group: 34). At the end of the PL-controlled study phase, all 3 main efficacy variables were statistically significantly improved in the Menthacarin group compared to PL. In the FU phase, former PL patients started to improve under Menthacarin treatment towards the outcomes seen in the former Menthacarin group (alignment at approximately 6 months), while former Menthacarin patients showed sustained or even continuously improved outcomes by month 12. At study end, more than 90% of patients were “much or very much improved" in both groups. Menthacarin treatment was well tolerated.
Conclusions The favorable effects seen in the FU period suggest that Menthacarin is a valuable treatment option in FD patients who require symptomatic treatment also in the longer term for up to 12 months.
... Nane ve kimyon uçucu yağlarının kombinasyonu, bağırsakta antispazmodik olarak kullanılır ve safra kesesi üzerinde rahatlatıcı etkiye sahiptir. 5,6 Kimyon uçucu yağı safra kesesinin kasılmasını engelleyerek safra kesesi hacmini %90 artırırken, Rosmarinus officinalis'in (biberiye) intravenöz infüzyonu hayvanlarda salgılanan safra hacmini iki katına çıkarmıştır. Biberiye ayrıca gaz giderici olarak ve hepatobiliyer sekresyonu uyarmak için kullanılır. ...
Essential oil is a dense essence and a mixture of terpenoid and non-terpenoid hydrocarbon substances produced by plants, animals, and microorganisms. Essential oils are used in skin diseases, insomnia, stress, headache, dyspeptic complaints, bacterial, viral, and fungal infections, the treatment of cancer, and for increasing concentration during the learning process. Besides their antibacterial, antifungal, anticholinergic, and antioxidant effects, many scientific studies have recently studied their effects
on the nervous system, urinary system infections, immune system, digestive system, and respiratory system. Aromatherapy aims to achieve emotional, physical, and spiritual balance by using the essential oils therapeutically. The safe and scientific-based administration of the aromatherapy methods by the healthcare professionals in a clinic would ensure that the individuals, who are increasingly interested in complementary therapies in modern society, could produce customized solutions and activate the self-healing power of their bodies, and that the human beings, whose essence is the nature, could surrender themselves as a whole together with their body, soul and mind, to the essential resource bearing the secrets of nature. In this part, diseases of the digestive system, which have a high prevalence in the population and negatively affect the health of individuals and their quality of life, will be presented along with the essential oils used and relevant studies.
... Wichtl (1994) reported that caraway promotes gastric secretion, stimulates appetite, and is used as a remedy for colic, loss of appetite and digestive disorders. Caraway oil inhibited the motor activities of SMC of the gallbladder, stomach, trachea and ileum (Boskabady et al., 2003;Micklefield et al., 2003). It is beneficial effect in relieving gastrointestinal symptoms associated with dyspepsia was reported (Al-Essa et al., 2010). ...
Since ancient times, the medicinal properties of plant material improve the quality of life. Medicinal plants and foods may provide phytotherapy a new dimension and enable their application to treat and prevention of diseases with the advantage of reducing chemical drugs. Historically, caraway, Chinese chives and cassia have enjoyed a rich tradition of use for flavouring, and medicinal purposes, because of wide range of secondary metabolites with potent antibacterial, antioxidant, antimicrobial, anti-inflammatory, anticancer and other tremendous benefits. In many countries, medicinal plants are widely used as functional foods and daily supplements with the aim of promoting public health and both preventing and curing diseases. The main characteristics, components, active substance and important pharmacological and health benefits of caraway, Chinese chives and cassia was reviewed.
... This spasmolytic action may partly explain the clinical benefit of peppermint oil. 5 In the stomach of healthy volunteers, peppermint oil decreased motility index in the fasting but not fed state but had no effect on gastric sensitivity to distension, basal muscle tone, or fundus accommodation. 6 Spasmolytic effects also occurred in the duodenum of healthy volunteers after application of peppermint and caraway oils at doses present in Menthacarin ® . 7 Data on the effects of caraway oil or its constituents on muscle activity in the intestine are not available. ...
Background
Herbal medicinal products with a broad activity spectrum may be promising alternatives to treat functional gastrointestinal disorders (FGD). Menthacarin® is a drug with a fixed combination of peppermint and caraway oils, which is clinically used to treat FGD‐associated symptoms.
Materials
We studied the effects of peppermint and caraway oils on contractile and secretory activity in 255 human small and large intestinal preparations derived from surgical resections (73 patients). Motility was recorded in circular smooth muscle strips and secretion with the Ussing chamber‐voltage clamp technique. Electrical field stimulation evoked nerve induced contractile responses.
Key Results
Peppermint and caraway oil concentrations dependently inhibited muscle contractility as indicated by sustained muscle relaxation and decrease in phasic contractility. These effects occurred in small and large intestinal preparations with IC50 values ranging between 17 and 90 µg/mL for peppermint oil and between 7 and 127 µg/mL for caraway oil. Neither peppermint nor caraway oil influenced the nerve evoked contractile response. The inhibition of contractile activity, but not the muscle relaxation, was prevented by the L‐type calcium channel activator Bay K8644 but not by the neurotoxin tetrodotoxin. Both peppermint oil and caraway oil increased epithelial secretion, which remained in tetrodotoxin.
Conclusion & Interference
The findings revealed a strong muscle inhibitory and pro‐secretory action of peppermint and caraway oils at clinically relevant concentrations. Both actions were nerve‐independent. The inhibition of contractility was mediated by inhibition of L‐type calcium channels. The effects on muscle and epithelial activity may contribute to the beneficial effects observed in patients with FGD.
... 48 Manometry and/or barostat studies have identified the following peppermint oil effects: decreased intragastric pressure, decreased gastric motility index, no effect on gastric accommodation. [49][50][51] In healthy volunteers, peppermint oil taken orally did not affect epigastric symptoms or satiation though there was decreased appetite (vs placebo) during the fasting period. 50 The effect of peppermint oil on gastric emptying has been evaluated with mixed results. ...
Background:
Peppermint oil has been used for centuries as a treatment for gastrointestinal ailments. It has been shown to have several effects on gastrointestinal physiology relevant to clinical care and management.
Aim:
To review the literature on peppermint oil regarding its metabolism, effects on gastrointestinal physiology, clinical use and efficacy, and safety.
Methods:
We performed a PubMed literature search using the following terms individually or in combination: peppermint, peppermint oil, pharmacokinetics, menthol, oesophagus, stomach, small intestine, gallbladder, colon, transit, dyspepsia, nausea, abdominal pain, and irritable bowel syndrome. Full manuscripts evaluating peppermint oil that were published through 15 July 2017 were reviewed. When evaluating therapeutic indications, only randomised clinical trials were included. References from selected manuscripts were used if relevant.
Results:
It appears that peppermint oil may have several mechanisms of action including: smooth muscle relaxation (via calcium channel blockade or direct enteric nervous system effects); visceral sensitivity modulation (via transient receptor potential cation channels); anti-microbial effects; anti-inflammatory activity; modulation of psychosocial distress. Peppermint oil has been found to affect oesophageal, gastric, small bowel, gall-bladder, and colonic physiology. It has been used to facilitate completion of colonoscopy and endoscopic retrograde cholangiopancreatography. Placebo controlled studies support its use in irritable bowel syndrome, functional dyspepsia, childhood functional abdominal pain, and post-operative nausea. Few adverse effects have been reported in peppermint oil trials.
Conclusion:
Peppermint oil is a natural product which affects physiology throughout the gastrointestinal tract, has been used successfully for several clinical disorders, and appears to have a good safety profile.
... Human clinical studies, experimental in vivo studies with laboratory animals as well as ex vivo and in vitro studies were included as well. To avoid the [143,[190][191][192] 34 [142,193] 35 [145] 36 [194] 37 [195] 38 [196,197] 39 [141] 40 [198] 41 [199] 42 [199] 43 [200] 44 [201] 45 [202] [175,185,203,204] 46 [205][206][207][208] 47 [209,210] 48 [189] 49 [176,[211][212][213][214][215][216] 50 [217] 51 [214] 52 [88,205,218] 53 [219] 54 [220] 55 [86,87,221,222] 56 [223] 57 [52,118,175,[224][225][226][227][228][229][230][231][232][233][234][235][236][237] 58 [238,239] 59 [240] 60 [241] 61 [242,243] 62 [244] 63 [245] 64 [244,246] 65 [247] 66 [248] 67 [249] 68 [175,250,251] 69 [252,253] 70 [251,254] 71 [255] 72 [53] 73 [256] 74 [257] 75 [258] 76 [259] 77 [180,[260][261][262] 78 [263] 79 [264] 80 [175,211,233,237,265] 81 [252] 82 [266][267][268] 83 [267,268] 84 [269] 85 [270] 86 [269] 87 [268] 88 [271] 89 [272] 90 [52, 118-120, 175, 176, 226, 250, 252, 273] 91 [274] 92 [113,275,276] 93 [277,278] 94 [279] 95 [280] 96 [191,281] 97 [185,282] 98 [145] 99 [283,284] risk of source selection bias, multiple types of sources were used initially: standard textbooks, peer-reviewed publications, a governmental report, and personal com- munications with experts. The risk of introducing data- base bias was reduced by using two different and independent databases and by using the Mesh Terms function of PubMed. ...
Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity is known for diarrhoea and for respiratory diseases in calves and piglets. Despite a highly diverse etiology and pathophysiology of these multifactorial diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants may bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs '. Regarding the plurality of medicinal plants, the aim of a systematic review was to identify the most promising medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases in calves and piglets. Based on nine initial sources including standard textbooks and European ethno-veterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20,000 peer-reviewed articles published in the last 20 years. This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L, Mentha x piperita L. and Salvia officinalis L; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L) KUNTZE and Glycyrrhiza glabra L. were identified as efficient candidates for modulation of the immune system and inflammation. Several medicinal plants bear a potential for novel treatment strategies for young livestock. The findings of this review provide a basis on plant selection for future studies.
... Human clinical studies, experimental in vivo studies with laboratory animals as well as ex vivo and in vitro studies were included as well. To avoid the [143,[190][191][192] 34 [142,193] 35 [145] 36 [194] 37 [195] 38 [196,197] 39 [141] 40 [198] 41 [199] 42 [199] 43 [200] 44 [201] 45 [202] [175,185,203,204] 46 [205][206][207][208] 47 [209,210] 48 [189] 49 [176,[211][212][213][214][215][216] 50 [217] 51 [214] 52 [88,205,218] 53 [219] 54 [220] 55 [86,87,221,222] 56 [223] 57 [52,118,175,[224][225][226][227][228][229][230][231][232][233][234][235][236][237] 58 [238,239] 59 [240] 60 [241] 61 [242,243] 62 [244] 63 [245] 64 [244,246] 65 [247] 66 [248] 67 [249] 68 [175,250,251] 69 [252,253] 70 [251,254] 71 [255] 72 [53] 73 [256] 74 [257] 75 [258] 76 [259] 77 [180,[260][261][262] 78 [263] 79 [264] 80 [175,211,233,237,265] 81 [252] 82 [266][267][268] 83 [267,268] 84 [269] 85 [270] 86 [269] 87 [268] 88 [271] 89 [272] 90 [52, 118-120, 175, 176, 226, 250, 252, 273] 91 [274] 92 [113,275,276] 93 [277,278] 94 [279] 95 [280] 96 [191,281] 97 [185,282] 98 [145] 99 [283,284] risk of source selection bias, multiple types of sources were used initially: standard textbooks, peer-reviewed publications, a governmental report, and personal com- munications with experts. The risk of introducing data- base bias was reduced by using two different and independent databases and by using the Mesh Terms function of PubMed. ...
... To avoid the Assessment = conclusion of a reference on a hypothesized effect; b reference = trial x plant species x indication; c particularly unspecified or infectious diarrhea and gastrointestinal spasms + = reference proves evidently the hypothesized effect; ? = reference shows uncertain hypothesized effect; o = reference does not prove evidently the hypothesized effect 1 [147, 148] [143,[190][191][192]34 [142, 193] 35 [145] 36 [194] 37 [195] 38 [196, 197] 39 [141] 40 [198] 41 [199] 42 [199] 43 [200] 44 [201] 45 [202] [175, 185, 203, 204] 46 [205][206][207][208]47 [209, 210] 48 [189] 49 [176,[211][212][213][214][215][216]50 [217] 51 [214] 52 [88, 205, 218] 53 [219] 54 [220] 55 [86, 87, 221, 222] 56 [223] 57 [52, 118, 175,[224][225][226][227][228][229][230][231][232][233][234][235][236][237]58 [238, 239] 59 [240] 60 [241] 61 [242, 243] 62 [244] 63 [245] 64 [244, 246] 65 [247] 66 [248] 67 [249] 68 [175, 250, 251] 69 [252, 253] 70 [251, 254] 71 [255] 72 [53] 73 [256] 74 [257] 75 [258] 76 [259] 77 [180,[260][261][262]78 [263] 79 [264] 80 [175, 211, 233, 237, 265] 81 [252] 82 [266][267][268]83 [267, 268] 84 [269] 85 [270] 86 [269] 87 [268] 88 [271] 89 [272] 90[52, 118–120, 175, 176, 226, 250, 252, 273] 91 [274] 92 [113, 275, 276] 93 [277, 278] 94 [279] 95 [280] 96 [191, 281] 97 [185, 282] 98 [145] 99 [283, 284] 100 [285] 101 [259] 102 [286] 103 [287] Sum of assessments in vitro 9 0 0 0 0 0 8 0 0 15 0 0 0 0 0 0 0 0 0 0 1 2 0 0 0 0 0 0 0 0 in vivo + clinical 2 0 0 0 0 1 2 0 1 2 0 0 2 0 0 7 0 0 2 0 0 2 0 0 1 0 0 4 0 2 a Assessment = conclusion of a reference on a hypothesized effect; b reference = trial x plant species x indication; + = reference proves evidently the hypothesized effect; ? = reference shows uncertain hypothesized effect; o = reference does not prove evidently the hypothesized effect 1 [288, 289] 2 [290] 3 [291] 4 [292] risk of source selection bias, multiple types of sources were used initially: standard textbooks, peer-reviewed publications, a governmental report, and personal communications with experts. ...
Background:
Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35 %; piglets ≤ 50 %) and for respiratory diseases (calves ≤ 80 %; piglets ≤ 40 %). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs'. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets.
Results:
Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20'000 peer-reviewed articles published in the last 20 years (1994-2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation.
Conclusions:
Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies.
... To avoid the Assessment = conclusion of a reference on a hypothesized effect; b reference = trial x plant species x indication; c particularly unspecified or infectious diarrhea and gastrointestinal spasms + = reference proves evidently the hypothesized effect; ? = reference shows uncertain hypothesized effect; o = reference does not prove evidently the hypothesized effect 1 [147, 148] [143,[190][191][192]34 [142, 193] 35 [145] 36 [194] 37 [195] 38 [196, 197] 39 [141] 40 [198] 41 [199] 42 [199] 43 [200] 44 [201] 45 [202] [175, 185, 203, 204] 46 [205][206][207][208]47 [209, 210] 48 [189] 49 [176,[211][212][213][214][215][216]50 [217] 51 [214] 52 [88, 205, 218] 53 [219] 54 [220] 55 [86, 87, 221, 222] 56 [223] 57 [52, 118, 175,[224][225][226][227][228][229][230][231][232][233][234][235][236][237]58 [238, 239] 59 [240] 60 [241] 61 [242, 243] 62 [244] 63 [245] 64 [244, 246] 65 [247] 66 [248] 67 [249] 68 [175, 250, 251] 69 [252, 253] 70 [251, 254] 71 [255] 72 [53] 73 [256] 74 [257] 75 [258] 76 [259] 77 [180,[260][261][262]78 [263] 79 [264] 80 [175, 211, 233, 237, 265] 81 [252] 82 [266][267][268]83 [267, 268] 84 [269] 85 [270] 86 [269] 87 [268] 88 [271] 89 [272] 90[52, 118–120, 175, 176, 226, 250, 252, 273] 91 [274] 92 [113, 275, 276] 93 [277, 278] 94 [279] 95 [280] 96 [191, 281] 97 [185, 282] 98 [145] 99 [283, 284] 100 [285] 101 [259] 102 [286] 103 [287] 104 [286] Sum of assessments in vitro 9 0 0 0 0 0 8 0 0 15 0 0 0 0 0 0 0 0 0 0 1 2 0 0 0 0 0 0 0 0 in vivo + clinical 2 0 0 0 0 1 2 0 1 2 0 0 2 0 0 7 0 0 2 0 0 2 0 0 1 0 0 4 0 2 a Assessment = conclusion of a reference on a hypothesized effect; b reference = trial x plant species x indication; + = reference proves evidently the hypothesized effect; ? = reference shows uncertain hypothesized effect; o = reference does not prove evidently the hypothesized effect 1 [288, 289] 2 [290] 3 [291] 4 [292] risk of source selection bias, multiple types of sources were used initially: standard textbooks, peer-reviewed publications, a governmental report, and personal communications with experts. ...
... Since peppermint oil is assumed to be less effective on other gastrointestinal conditions, the accidental recruitment of people with symptoms of IBS caused by other conditions might have been responsible for such inconsistencies (Alam et al., 2013). Micklefield et al. showed that a mixture of cumin and mint was effective on relaxing the smooth muscles of the intestine and reducing the symptoms of functional dyspepsia (Micklefield, Jung, Greving, & May, 2003). Spirling and Daniels suggested that taking mint after meals could decrease gastrointestinal reactions and relieve the symptoms of dyspepsia (such as flatulence, belching, and abdominal distention) and colon spasms (Spirling & Daniels, 2001). ...
CONTEXT: Gastrointestinal problems are common after Cesarean section. During the past three decades, there has been an increasing trend in the use of herbal plants in the treatment of various medical conditions.AIMS: This study aimed to compare the effects of cumin, peppermint with magnesium hydroxide (milk of magnesia; MOM) on gastrointestinal complications of Caesarean section.SETTINGS & DESIGN: This randomized double-blind controlled trial was conducted in the Gynecology and Obstetrics Department of Imam Hospital (affiliated to Mazandaran University of Medical Sciences, Sari, Iran) during November 2013-August 2014. The project was approved by the Research Ethics Committee of Islamic Azad Medical University, Sari Branch (Iran).MATERIAL & METHODS: A total of 83 patients undergoing non-emergency Cesarean delivery in Imam Hospital were randomly selected. Patients with underlying diseases, history of gastrointestinal problems, fever, intestinal adhesion, longer-than-usual Cesarean section, and lack of cooperation were excluded. The subjects were informed about the study objectives and procedure and asked to provide written informed consent. They were then randomly assigned into three groups of cumin, peppermint, MOM. Gastrointestinal complications were assessed 20, 40, 60, and 120 minutes after drug administration.STATISTICAL ANALYSIS USED: The collected data were analyzed using Fisher’s exact and chi-square tests in SPSS for Windows 18.0.RESULTS: There was no significant difference between three groups according to incidence of gastrointestinal side effects after Cesarean section at the mentioned intervals.CONCLUSIONS: Cumin and peppermint were as effective as MOM.
... Also, Inoue et al. (2002) and Satsu et al. (2004) reported anti allergic effects of this herb. Furthermore, previous studies have been shown anti-inflammatory, analgesic and antispasmodic effects of M. piperita (Atta & Alkofahi, 1998; Göbel et al., 1995, 1996 Juergens et al., 1998; Asao et al., 2003; Hiki et al., 2003; Micklefield et al., 2003). Also Tate et al. (1997) reported anti nausea effect of this herb. ...
... Micklefield et al. (2000) also found a decreased number of duodenal contractions and contraction amplitudes in six patients measured with a manometer after the administration of a capsule containing 90 mg peppermint oil plus 50 mg caraway oil. In a follow up study of 24 patients, a capsule containing 90 mg of peppermint oil alone was also able to reduce significantly the frequency and duration of duodenal contractions and the duration of contractions in the gastric corpus, producing smooth-muscle relaxation in the stomach and duodenum (Micklefield et al., 2003). Abdominal pain and dyspepsia have been found to respond well to treatment with either peppermint leaves (Table 1 ) or oil. ...
Peppermint (Mentha piperita L.) is one of the most widely consumed single ingredient herbal teas, or tisanes. Peppermint tea, brewed from the plant leaves, and the essential oil of peppermint are used in traditional medicines. Evidence-based research regarding the bioactivity of this herb is reviewed. The phenolic constituents of the leaves include rosmarinic acid and several flavonoids, primarily eriocitrin, luteolin and hesperidin. The main volatile components of the essential oil are menthol and menthone. In vitro, peppermint has significant antimicrobial and antiviral activities, strong antioxidant and antitumor actions, and some antiallergenic potential. Animal model studies demonstrate a relaxation effect on gastrointestinal (GI) tissue, analgesic and anesthetic effects in the central and peripheral nervous system, immunomodulating actions and chemopreventive potential. Human studies on the GI, respiratory tract and analgesic effects of peppermint oil and its constituents have been reported. Several clinical trials examining the effects of peppermint oil on irritable bowel syndrome (IBS) symptoms have been conducted. However, human studies of peppermint leaf are limited and clinical trials of peppermint tea are absent. Adverse reactions to peppermint tea have not been reported, although caution has been urged for peppermint oil therapy in patients with GI reflux, hiatal hernia or kidney stones.
... Also, Inoue et al. (2002) and Satsu et al. (2004) reported anti allergic effects of this herb. Furthermore, previous studies have been shown anti-inflammatory, analgesic and antispasmodic effects of M. piperita (Atta & Alkofahi, 1998;Göbel et al., 1995Göbel et al., , 1996Juergens et al., 1998;Asao et al., 2003;Hiki et al., 2003;Micklefield et al., 2003). Also Tate et al. (1997) reported anti nausea effect of this herb. ...
... Mint essential oils are also known to possess psychoactive actions (Umezu et al., 2001). Peppermint oil can be efficiently used in replacement of the synthetic drugs to reduce hyperperistaltic state in patient's stomach during endoscopy treatment (Asao et al., 2003;Micklefield et al., 2003). Mentha oils are enriched in monoterpenes and are being used in food, cosmetics and pharmaceutical industry (Bhat et al., 2002). ...
... Also, Inoue et al. (2002) and Satsu et al. (2004) reported anti allergic effects of this herb. Furthermore, previous studies have been shown anti-inflammatory, analgesic and antispasmodic effects of M. piperita (Atta & Alkofahi, 1998;Göbel et al., 1995Göbel et al., , 1996Juergens et al., 1998;Asao et al., 2003;Hiki et al., 2003;Micklefield et al., 2003). Also Tate et al. (1997) reported anti nausea effect of this herb. ...
Mentha piperita (Labiatae), commonly known as peppermint is a native Iranian herb which is used in folk medicine for various purposes. This study was carried out to reveal the teratogenic effect of Mentha piperita on mice fetuses. In this experimental study, pregnant Balb/c mice divided to four groups. Case group received 600 (treatment I) and 1200 (treatment 11) mg/kg/day the hydroalcoholic extract of Mentha piperita during 6-15 of gestational days and one control group received normal saline during GD6-GD15 by gavages and other control group did not receive any matter during 6-15 of gestational days. Mice sacrificed at GD18 and embryos were collected. Macroscopic observation was done by stereomicroscope. 20 fetuses of each group were stained by Alizarin red-S and Alcian blue staining method. The Mean weight of fetuses decreased in treatment groups rather than control (P<0.05) but CRL there was no significant difference between treatments and controls groups. In the treatment I (600 mg/kg/day) and treatment 11 (1200 mg/kg/day), normal saline and control group, no gross congenital malformations were observed in fetuses. Treated fetuses also had no delayed bone ossification as determined by Alizarin red-S and Alcian blue staining method. This study showed that the hydroalcoholic extract of Mentha piperita (600 and 1200 mg/kg/day) has no teratogenic effect in mice fetuses if used continuously during embryonic period.
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.
Introduction
Functional dyspepsia (FD) is a prevalent, but frequently overlooked and/or under diagnosed disorder of gut-brain interaction (DGBI). Functional dyspepsia frequently co-exists with other DGBIs, and persistent symptoms have a significant impact on patients’ quality of life. A variety of therapies (e.g. diet, probiotics, antibiotics, acid suppressants, neuromodulators, prokinetics) are employed to treat the multiple symptoms of FD, although none are uniformly effective.
Areas covered
This review covers currently available therapies for the treatment of FD in addition to novel and emerging therapies that may change the treatment paradigm in the near future. PubMed, Embase and the Cochrane data bank were searched from 1990 to October 2022 for relevant articles.
Expert opinion
Dietary intervention, eradication of H. pylori, and/or a trial of acid suppression are reasonable initial treatment options for patients with FD. Neuromodulators and fundic accommodation agents are underemployed and should be used more routinely by healthcare providers, especially for patients with moderate-severe symptoms. Alternative therapies, such as cognitive behavioral therapy and hypnotherapy, are gaining recognition as safe and effective treatments for FD and can be used alone or in combination with medications. Virtual reality has the potential to significantly improve global FD symptoms.
Nutritional ingredients, including various fibers, herbs, and botanicals, have been historically used for various ailments. Their enduring appeal is predicated on the desire both for more natural approaches to health and to mitigate potential side effects of more mainstream treatments. Their use in individuals experiencing upper gastrointestinal (GI) complaints is of particular interest in the scientific space as well as the consumer market but requires review to better understand their potential effectiveness. The aim of this paper is to review the published scientific literature on nutritional ingredients for the management of upper GI complaints. We selected nutritional ingredients on the basis of mentions within the published literature and familiarity with recurrent components of consumer products currently marketed. A predefined literature search was conducted in Embase, Medline, Derwent drug file, ToXfile, and PubMed databases with specific nutritional ingredients and search terms related to upper GI health along with a manual search for each ingredient. Of our literature search, 16 human clinical studies including nine ingredients met our inclusion criteria and were assessed in this review. Products of interest within these studies subsumed the categories of botanicals, including fiber and combinations, and non-botanical extracts. Although there are a few ingredients with robust scientific evidence, such as ginger and a combination of peppermint and caraway oil, there are others, such as melatonin and marine alginate, with moderate evidence, and still others with limited scientific substantiation, such as galactomannan, fenugreek, and zinc-l-carnosine. Importantly, the paucity of high-quality data for the majority of the ingredients analyzed herein suggests ample opportunity for further study. In particular, trials with appropriate controls examining dose–response using standardized extracts and testing for specific benefits would yield precise and effective data to aid those with upper GI symptoms and conditions.
Background
Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in‐depth review of this is timely.
Aims/Purpose
To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia.
Methods
We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated.
Results
We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well‐defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation.
Conclusions
We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation.
Introduction
According to Rome IV, functional dyspepsia is diagnosed with presence of dyspepsia in the absence of organic or metabolic causes. FD caused by several factors such as impaired gastric accommodation and hypersensitivity to gastric distention. Several studies have reported effectiveness of herbal medicine on FD. This article, thus, reviews Persian herbal medicine in FD.
Method
Electronic databases including Pubmed, Scopus, Cochrain, Embase, Web of science and Ovid were searched so as to find clinical articles related to dyspepsia and herbal medicine by July 2019. Our search strategies were traditional medicine, complementary and alternative medicine, herb, plant, and dyspepsia. We excluded all articles except Persian clinical trials.
Results
We found 34 clinical trials with 15 herbs and 4 compound herbal remedies like Asparagus racemosus, Brassica oleracea, Cynara scolymus, Ocimum basilicum, Mentha longifolia, Mentha pulegium, Mentha piperata, Pimpinella anisum, Nigella sativa, Mastic gum, Curcuma longa, Pistatio atlantica, Glycyrrhiza glabra, Solanum tuberosum and Zingiber officinale and compound remedies of Rosa damascene & Crocus sativus, Trachyspermum copticom & Apium graveolence, Carum carvi & Mentha pipperata, Gingiber officinalis & Cynara scolymus are effective in functional dyspepsia.
Conclusion
Many people use herbal and traditional remedies for treatment of disorders such as gastrointestinal disordersو , especially in Asian countries. Several studies reported the efficacy of herbal medicine in functional dyspepsia. Although their mechanisms are not fully understood, it seems they can modulate GI motility and improve symptoms of FD.
Zusammenfassung
Das ätherische Kümmelöl aus Carum carvi L., Carvi aetheroleum, bestehend überwiegend aus den Terpenen (S)-(+)-Carvon und (R)-(+)-Limonen, wird bei Verdauungsbeschwerden, einhergehend mit Blähungen und Flatulenz, oder sogar bei flatulenzbedingten Koliken angewandt. Überwiegend aktuelle experimentelle Daten geben Hinweise oder bekräftigen die bereits früher postulierten Wirkungen. Zu nennen sind vor allem karminative (entblähende) Wirkungen im Gastrointestinum durch spasmolytische bzw. entkrampfende Eigenschaften, eine mögliche Hemmung der intestinalen Gärungsprozesse durch antimikrobielle (auf pathogene Keime beschränkt) Wirkungen, eine Volumenreduktion durch Hemmung der Schaumbildung von Magen- und Darmsaft und damit eine mögliche Reduktion blähungsbedingter Schmerzen sowie direkte antinozizeptive Eigenschaften. Ergebnisse aus klinischen Untersuchungen und Studien können die Wirkungen z. T. für das Kümmelöl alleine, besser für eine langjährig bewährte Kombination zusammen mit Pfefferminzöl, z. B. in der Anwendung bei typischen Symptomen funktioneller Verdauungsstörungen bestätigen.
Introduction: Functional Dyspepsia (FD), defined as chronic symptoms originating from the gastroduodenal region in absence of readily identifiable organic disease, is one of the most common gastrointestinal disorders. FD is divided into two subgroups: Post-Prandial Distress Syndrome (PDS) or meal-related FD, characterized by postprandial fullness and early satiation, and Epigastric Pain Syndrome (EPS) or meal-unrelated FD, characterized by epigastric pain and burning.
Areas covered: This review summarizes the existing and off-label therapeutic options for FD.
Expert opinion: The identification of mechanisms, the Rome IV classification, the reduction of PDS/EPS overlap and pictograms for symptom identification allow a better diagnosis and a more targeted treatment choice. Acotiamide, a first-in-class prokinetic agent available only in Japan and India, is the only agent of proven efficacy for FD, but clinicians use acid-suppressive therapy, prokinetics, neuromodulators and herbal therapies for treating FD symptoms. New emerging targets are duodenal low-grade inflammation with eosinophils and duodenal or other modified luminal microbiota.
Introduction
Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenum, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Despite its prevalence, therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low grade duodenal inflammation.
Areas covered
This review summarizes recent and ongoing drug development for FD as identified from a literature search was conducted on Pubmed and other sources.
Expert opinion
Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassium-competitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may also be efficacious in PDS. There are emerging data with pro- and antibiotics and several studies with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.
Background
Functional dyspepsia, consisting of epigastric pain syndrome and postprandial distress syndrome, is a prevalent functional gastrointestinal disorder. To date, only limited treatment options are available and conflicting results in terms of efficacy have been reported. Consequently, nonpharmacological treatment options are increasingly being explored for functional dyspepsia.
Aim
To provide an overview of current pharmacological and nonpharmacological treatment options for functional dyspepsia.
Methods
A literature search was conducted on Pubmed and other sources to identify relevant studies.
Results
Acid suppressive therapy reduced symptoms in 30%‐70% of the patients, with higher benefit in epigastric pain syndrome and superior effectiveness for proton pump inhibitors compared to H2‐antagonists. Prokinetic agents, primarily used to treat postprandial distress syndrome, showed variable efficiency: 59%‐81% responder rate for dopamine receptor antagonists, 32%‐91% for serotonin‐4‐receptor agonists and 31%‐80% for muscarinic receptor antagonists. H Pylori eradication, recommended in infected patients, was effective in 24%‐82%. Refractory symptoms are addressed with neuromodulators. However, their efficacy in functional dyspepsia remains incompletely elucidated, available data showing symptom reduction in 27%‐71% of the patients. Regarding herbal agents, peppermint oil reduced symptoms in 66%‐91%, rikkunshito in 29%‐34% and iberogast in 20%‐95%. Lastly, acupuncture, cognitive behavioural therapy and hypnotherapy may help to provide symptom control, but research on their efficacy remains sparse.
Conclusions
None of the available therapies is effective in the majority of patients without being associated with major side effects. Developing new treatment options is challenging due to the heterogeneity of functional dyspepsia, the lack of readily identified target mechanisms and the poor association between pathophysiological disturbances and symptoms.
Background
Anti-cholinergic agents may be used to inhibit duodenal peristalsis, but they may have adverse effects. Shakuyakukanzoto (Shao Yao Gan Cao Tang) has an anti-spasmodic effect and has been used before for oesophagogastroduodenoscopy and colonoscopy. This randomised clinical trial aimed to evaluate the inhibitory effect of Shakuyakukanzoto on duodenal peristalsis, and its usefulness when administered into the duodenum just before endoscopic retrograde cholangiopancreatography (ERCP). Methods
Participants were recruited between June 2008 and December 2010. All were aged ≥18 years and provided written informed consent. Exclusion criteria were: acute pancreatitis, a history of ischemic heart disease, prostatic hypertrophy or glaucoma, and altered/postsurgical upper gastrointestinal anatomy. The recruited participants were randomly assigned to the Shakuyakukanzoto group and control group. Shakuyakukanzoto 100 mg/mL solution or placebo (warm water) was administered directly as a spray into the duodenum during endoscopy. Efficacy was evaluated by observing the extent of duodenal peristalsis and assessing the difficulty of cannulating the common bile duct, the required time (RT) from administration to inhibition of duodenal peristalsis and the stop duration time (DT, the duration for which peristalsis was inhibited). Side effects were evaluated by measuring serum potassium concentration after ERCP. ResultsOf 28 participants, 15 were assigned to the Shakuyakukanzoto group and 13 to the control group. Duodenal peristalsis was inhibited in eight of the 10 eligible participants (80.0%) in the Shakuyakukanzoto group and none (0%) of the nine eligible participants in the control group (P = 0.026). In the Shakuyakukanzoto group, mean RT (±standard deviation) was 76.0 ± 23.9 s and DT was 11.3 ± 4.2 min. No adverse effects were observed in the Shakuyakukanzoto group during or after ERCP. Conclusion
Duodenal peristalsis can be inhibited by spraying Shakuyakukanzoto solution directly into the duodenum.Trial registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000011469
The leaves and the essential oil of peppermint, Mentha × piperita L., have traditionally been used as carminative and antispasmodic herbal drugs. Spasmolytic effects of the essential oil have been demonstrated both in vitro on isolated gut segments and in vivo on healthy volunteers and in gastrointestinal endoscopy. In short-term studies, peppermint oil was revealed to be superior to a placebo in the treatment of irritable bowel syndrome. Due to the lack of well designed and carefully executed long-term studies, the significance of peppermint oil in the treatment of irritable bowel syndrome has not yet been elucidated. Menthol, the main component of peppermint oil, contributes to its spasmolytic effect. In human plasma and urine, mentholglucuronide has been detected as its main metabolite. Aqueous extracts from peppermint leaves show antiulcerogenic and cholagogic effects. In combination with the spasmolytic properties of the essential oil, hydrophilic compounds may contribute to the efficacy of peppermint leaves on spasmodic discomfort in the gastrointestinal and biliary system.
For many, the term “aromatherapy” originally became associated with the concept of the holistic use of essential oils to promote health and well-being. As time has progressed and the psychophysiological effects of essential oils have been explored further, their uses to reduce anxiety and aid sedation have also become associated with the term. This is especially so since the therapy has moved into the field of nursing, where such activities are of obvious benefit to patients in a hospital environment. More importantly, the practice of aromatherapy (in English-speaking countries) is firmly linked to the inhalation of small doses of essential oils and their application to the skin in high dilution as part of an aromatherapy massage.
Danshu capsule (DSC) is a medicinal compound in traditional Chinese medicine (TCM). It is commonly used for the treatment of acute & chronic cholecystitis as well as choleithiasis. To study its choleretic effect, healthy rats were randomly divided into DSC high (DSCH, 900mg/kg), medium (DSCM, 450mg/kg), and low (DSCL, 225mg/kg) group, Xiaoyan Lidan tablet (XYLDT, 750mg/kg), and saline group. The bile was collected for 1h after 20-minute stabilization as the base level, and at 1h, 2h, 3h, and 4h after drug administration, respectively. Bile volume, total cholesterol, and total bile acid were measured at each time point. The results revealed that DSC significantly stimulated bile secretion, decreased total cholesterol level and increased total bile acid level. Therefore, it had choleretic effects. To identify the active components contributing to its choleretic effects, five major constituents which are menthol (39.33mg/kg), menthone (18.02mg/kg), isomenthone (8.18mg/kg), pluegone (3.31mg/kg), and limonene (4.39mg/kg) were tested on our rat model. The results showed that menthol and limonene could promote bile secretion when compared to DSC treatment (p > 0.05); Menthol, menthol and limonene could significantly decrease total cholesterol level (p<0.05 or p<0.01) as well as increase total bile acid level (p<0.05 or p<0.01); Isomenthone, as a isomer of menthone, existed slightly choleretic effects; Pluegone had no obvious role in bile acid efflux. These findings indicated that the choleretic effects of DSC may be attributed mainly to its three major constituents: menthol, menthone and limonene.
Copyright © 2014. Published by Elsevier B.V.
Herbal medications are considered as integral part of complementary and alternative medicine (CAM). CAM is a group of diverse medical and healthcare systems, practices, and products that are not presently considered to be part of conventional medicine. Several studies have reported that between 30 and 40% of the general North American population are currently using, or have used CAM. Furthermore, over 50% of patients which require health care use CAM either alone or in conjunction with conventional medications. Most importantly, almost 20% of the patients that consult a physician are taking herbal medications.
Patients, and in some cases health care providers as well, are not fully aware of the health risks incurred by ingestion of these compounds, either due to their potential adverse effects, or to their pharmacological interactions with other medications prescribed by the physician. This situation is further compounded by the fact that, at least, 60% of the patients taking herbal medications do not disclose this fact to their physician.
This course provides the knowledge and tools, required for the clinician to discuss natural health products with patients and other members of the health care team. It also discusses the need for the physician to actively inquire if the patient is taking herbal medications, and take that into account prior to prescribing new medications.
A brief historical background and an overview of regulatory bodies responsible for overseeing herbal medications are provided. Relevant examples of widely used herbal compounds are presented. Clinically relevant information on commonly used herbal medications regarding therapeutic effectiveness, pharmacological mechanism of action, adverse effects and drug interactions are reviewed based on scientific evidence.
Irritable bowel syndrome is a complex disorder whose pathophysiology involves alterations in the enteric microbiota, visceral hypersensitivity, gut immune/barrier function, hypothalamic-pituitary-adrenal axis regulation, neurotransmitters, stress response, psychological factors, and more. The importance of diet in the management of irritable bowel syndrome has taken center stage in recent times as the literature validates the relationship of certain foods with the provocation of symptoms. Likewise, a number of elimination dietary programs have been successful in alleviating irritable bowel syndrome symptoms. Knowledge of the dietary management strategies for irritable bowel syndrome will help guide nutritionists and healthcare practitioners to deliver optimal outcomes. This tutorial reviews the nutrition management strategies for irritable bowel syndrome.
Symptom relief in functional gastrointestinal disorders (FGID) is frequently sought with complementary and alternative medicine, and various herbal medicine compounds are popular in different parts of the world. Only a few products, however, are standardized and are backed by scientific evidence. This review mainly focuses on mechanistic and clinical data in support of the Japanese traditional compound Rikkunshi-to (RKT) and of STW-5. Their effects on gut sensori-motor function, neurohormonal network, and controlled clinical data in FGID are revised. RKT and STW-5 appear to possess some degree of gastroprokinetic, visceral analgesic properties, and seem to increase the gastric accommodation response. Controlled trials of RKT and STW-5 support at least a modest effect on symptoms of functional dyspepsia and irritable bowel syndrome, with low side effects profile. With the widespread use of herbals and the relative paucity of effective pharmacological options for FGID, rigorous studies to further elucidate pharmacological actions and clinical applications of herbal compounds are a priority.
Herbal treatments have a long standing tradition for a range of gastrointestinal conditions. In contrast, the scientific evidence for the use of herbal preparations is mixed. Available studies are plagued by methodological limitations. For functional gastrointestinal disorders there is evidence for the use of some well characterized preparations. In inflammatory bowel disease (IBD) there are limited placebo controlled trials, other studies use active controls with suboptimal doses of the comparators.
Aside from patchy evidence supporting the use of herbal medicines, it is also of importance to consider that plants and plant extracts contain constituents that may vary depending upon environmental conditions during growth. Variable environmental conditions may affect the composition and the concentration of the active ingredients. In addition, most herbs provide a variable plethora of chemical families with medicinal utility. While these ingredients might be of benefit, the concentration and dose of these constituents needs to be closely monitored. Nevertheless, many herbal preparations are marketed without evidence for stringent adherence to good manufacturing practice (GMP) guidelines. Thus physicians and regulators should be very cautious with the use of these remedies. Appropriate scientific evidence for the claimed clinical benefits should become mandatory. In addition, the standards for production and safety monitoring should comply with established standards for chemically defined products. With these processes in mind the full value of herbal remedies may come to light particularly as the bioactive compounds present in these preparations become recognized.
Menthol, the main active constituent of peppermint oil, exerts gut spasmolytic effects, although its mechanism of action remains unclear. We investigated the effects of menthol on gastric emptying and spontaneous- or evoked- mechanical activity of whole murine stomach. Gastric emptying was calculated after i.p. administration of menthol (50mg/Kg). Responses induced by menthol on gastric intraluminal pressure and evoked-cholinergic contractions were analysed in vitro. Menthol decreased the gastric emptying rate. In vitro, menthol (0.3-30mM) produced a concentration-dependent relaxation of whole stomach, that was significantly reduced by tetrodotoxin or ω-conotoxin GVIA. The gastric relaxant responses were not affected by Nω-nitro-L-arginine methyl ester, inhibitor of nitric oxide-synthase, apamin or [Lys1,Pro2,5,Arg3,4,Tyr6]vasoactive intestinal peptide (VIP)(7-28), a VIP receptor antagonist, but they were significantly antagonized by atropine or guanethidine, a blocker of adrenergic neurotransmission. The joint application of atropine and guanethidine did not produce any additive effects on menthol effects. Phentolamine, an α-adrenoceptor antagonist, but not propranolol, a β-adrenoceptor antagonist, significantly reduced menthol responses and the contemporary administration of both adrenergic antagonists did not produce additive effects. Menthol (1-100μM) produced a reduction of the electrically-evoked cholinergic contractions, which was prevented by guanethidine. Menthol did not affect the contractions induced by carbachol. In conclusion, menthol in mouse, is able to reduce the rate of gastric emptying and to relax the stomach in vitro. The latter effect appears due, almost in part, to neural mechanisms, with involvement of α-adrenoceptors leading to reduction of tonic ongoing release of acetylcholine.
Background:
Menthol reduces intestinal motility in animal studies, an effect that is probably mediated by transient receptor potential channels. Peppermint oil (PO), with menthol as a major constituent, is widely used as a spasmolytic agent in irritable bowel syndrome. In the current study, we investigated the effect of acute PO administration on intragastric pressure (IGP) profiles and gastric sensorimotor functions in health.
Methods:
Healthy volunteers underwent IGP measurement before and during continuous intragastric infusion of a nutrient drink (n = 13), and gastric barostat studies (n = 13). A single capsule of PO (182 mg) or placebo was administered during the studies in a randomized controlled crossover design. Throughout the studies, healthy volunteers scored 11 epigastric symptoms on a visual analogue scale (VAS); satiation was scored on a 6-point Likert scale during intragastric infusion.
Key results:
During fasting, IGP and motility index (MI) of the proximal stomach decreased significantly after PO administration compared with placebo (P < 0.0001 and <0.05, respectively). In contrast, during intragastric infusion of the nutrient drink, no significant differences were detected between PO and placebo in IGP profiles, MI, satiation scores, and epigastric symptoms. The maximum infused volume, gastric compliance or sensitivity to balloon distention did not differ between both treatment arms. However, reduced appetite scores were seen during fasting after PO treatment, as compared with placebo (P = 0.01). Postprandial VAS scores were similar between PO and placebo.
Conclusions & inferences:
Peppermint oil reduces IGP, proximal phasic contractility, and appetite, with negligible effects on gastric sensitivity, tone, accommodation, and nutrient tolerance in health.
The effectiveness of topical peppermint oil added to barium sulphate suspension in relieving colonic muscle spasm during double contrast barium enema examination was assessed in a double blind study. 141 patients were randomized either to a control group (71 patients) examined with standard barium suspension or to the treatment group which received peppermint oil mixed with the barium preparation. No residual spasm was evident in a significant proportion of patients in the treated group (60%) compared with the control group (35%) (p < 0.001). The patients' acceptability of the procedure was good and there were no adverse effects on the overall quality of the examination. In conclusion, the addition of peppermint oil to the barium suspension seems to reduce the incidence of colonic spasm during the examination. The technique is simple, safe, cheap and it may lessen the need for intravenous administration of spasmolytic agents.
An investigation of the mechanism of peppermint oil action was performed using isolated pharmacological preparations from guinea pig large intestine and patch clamp electrophysiology techniques on rabbit jejunum. Peppermint oil relaxed carbachol-contracted guinea pig taenia coli (IC50, 22.1 μg/mL) and inhibited spontaneous activity in the guinea pig colon (IC50, 25.9 μg/mL) and rabbit jejunum (IC50, 15.2 μg/mL). Peppermint oil markedly attenuated contractile responses in the guinea pig taenia coli to acetylcholine, histamine, 5-hydroxytryptamine, and substance P. Peppermint oil reduced contractions evoked by potassium depolarization and calcium contractions evoked in depolarizing Krebs solutions in taenia coli. Potential-dependent calcium currents recorded using the whole cell clamp configuration in rabbit jejunum smooth muscle cells were inhibited by peppermint oil in a concentration-dependent manner. Peppermint oil both reduced peak current amplitude and increased the rate of current decay. The effect of peppermint oil resembled that of the dihydropyridine calcium antagonists. It is concluded that peppermint oil relaxes gastrointestinal smooth muscle by reducing calcium influx.
An investigation of the mechanism of peppermint oil action was performed using isolated pharmacological preparations from guinea pig large intestine and patch clamp electrophysiology techniques on rabbit jejunum. Peppermint oil relaxed carbachol-contracted guinea pig taenia coli (IC50, 22.1 micrograms/mL) and inhibited spontaneous activity in the guinea pig colon (IC50, 25.9 micrograms/mL) and rabbit jejunum (IC50, 15.2 micrograms/mL). Peppermint oil markedly attenuated contractile responses in the guinea pig taenia coli to acetylcholine, histamine, 5-hydroxytryptamine, and substance P. Peppermint oil reduced contractions evoked by potassium depolarization and calcium contractions evoked in depolarizing Krebs solutions in taenia coli. Potential-dependent calcium currents recorded using the whole cell clamp configuration in rabbit jejunum smooth muscle cells were inhibited by peppermint oil in a concentration-dependent manner. Peppermint oil both reduced peak current amplitude and increased the rate of current decay. The effect of peppermint oil resembled that of the dihydropyridine calcium antagonists. It is concluded that peppermint oil relaxes gastrointestinal smooth muscle by reducing calcium influx.
The effects of volatile oils of 22 plants from 11 different families and of some of their constituents on tracheal and ileal smooth muscles were investigated. The results were compared with the relaxant effects of catecholamines and phosphodiesterase inhibitors. All of the oils had relaxant effects on the tracheal smooth muscle, the most potent were angelica root, clove, elecampane root, basil and balm leaves oil. 16 oils inhibited the phasic contractions of the ileal myenteric plexus-longitudinal muscle preparation, the most potent were elecampane root, clove, thyme, balm leaves and angelica root oil. 2 oils (anise and fennel) increased the phasic contractions, and 4 oils (bitter orange, caraway, mace, pepper) produced a marked increase in resting force (i.e. contracture). In regard to the relaxant effects, most of the 16 oils were more potent on the ileal than on the tracheal muscle. However, a small group of 4 oils (angelica root, clove, basil, black caraway) had a higher relaxant effect on the tracheal than on the ileal muscle. This was also found to be the case with eugenol, eugenol acetate and cinnamic aldehyde as well as with isoprenaline and phosphodiesterase inhibitors.
The irritable bowel syndrome and its variants appear to affect about one third of the population, but most sufferers do not see a doctor. Progress in our understanding of this disorder is hampered by imprecise definitions, and the lack of a pathophysiologic marker. There is evidence of abnormal gut motility and myoelectric activity, and a suggestion that nerves and hormones play an important role. Diet, emotions, and infections are undeniable, but variable, contributing factors. While academicians grapple with aetiology it is the physician's duty to precisely and positively diagnose the syndrome, so that he may explain an reassure. The irritable bowel syndrome is a great problem to doctors and patients because of the worry that symptoms might indicate serious pathology such as inflammatory bowel disease or cancer. The short term therapeutic response to placebo is very high and no diet or medication consistently outperforms it. Bran and other bulking agents seem safe and are probably most effective when constipation is present. Peppermint oil shows some promise, and anticholinergics may be tried in persistent postprandial symptoms. It is most important, in this lifelong condition, that the risks of investigation and treatment not exceed those of the disease. As only a minority of irritable bowel syndrome sufferers bring their complaints to a physician it is important to find out why the patient consults. The stressed, the unloved, and the cancer-phobic will have very different needs in diagnosis and in treatment.
Gastroparesis syndrome is a recognized complication of longstanding diabetes mellitus and is attributed to reduced gastric contractility due to ‘autovagotomy’. However, motor abnormalities associated with this syndrome may not be limited to the stomach. To test this hypothesis we have studied the fasting and fed manometric profiles of the proximal small intestine of fourteen patients with the clinical diagnosis of gastroparesis. Abnormal intestinal manometric patterns were observed in twelve out of the fourteen patients. In four patients there was reduced duodenojejunal phasic pressure activity, whereas in nine there were non-propagated long bursts of powerful contractions. Furthermore, while the majority of patients (eleven out of fourteen) exhibited the expected reduction in antral pressure activity and gastric phase III, a small subgroup of three patients exhibited a peculiar continuous 3 min-1 antral contractile activity.
Our findings show that the small intestine is frequently affected in patients with diabetic gastroparesis, and that the motility disorder both in the stomach and the small bowel is not invariably of a ‘paretic’ type. The occurrence of incoordinated intestinal long bursts and continuous antral activity suggests that disturbed sympathetic innervation participates in the aetiopathogenesis of their upper-gut dysfunction.
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.
Menthol-beta-D-glucuronide is a potential prodrug for colonic delivery of the spasmolytic agent menthol. Menthol is the primary constituent of peppermint oil, which is used to treat the irritable bowel syndrome. The chemical stability of menthol-beta-D-glucuronide was assessed at various pHs (1.5, 4.5, 6.0 and 7.4) over a 4 to 24 h period at 37 degrees C. The prodrug was stable, i.e., there was less than 0.1% hydrolysis of the prodrug, at pHs of 4.5, 6.0 and 7.4. At pH 1.5, the prodrug was about 20% hydrolyzed over a 4 h period suggesting the need for an enteric coating to prevent premature hydrolysis in the stomach. The stability of the prodrug was also assessed in luminal contents of the laboratory rat and in human stool samples. These studies were performed at concentrations designed to assess relative velocities of hydrolysis (i.e., substrate concentrations in excess of the Km). The prodrug was stable in luminal contents of the rat stomach, proximal small intestine, and the distal small intestine. The rate of hydrolysis of menthol-beta-D-glucuronide was 6.26 +/- 2.88 nmol min-1 mg-1 and 2.34 +/- 1.22 nmol min-1 mg-1 in luminal contents of the rat cecum and colon, respectively. The hydrolysis rate of menthol-beta-D-glucuronide was lower in human stool samples (0.52 +/- 0.46 nmol min-1 mg-1). The prodrug had a measured log octanol/buffer partition coefficient of -1.61 suggesting it should be poorly absorbed from the lumen of the gastrointestinal tract. The data support the hypothesis that menthol-beta-D-glucuronide is a candidate for the delivery of menthol to the large intestine under in vivo conditions.
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.
The aim of this double-blind crossover study was to evaluate the effects of oral erythromycin (250 mg t.i.d.) on fasting and postprandial gastrointestinal motility and gastrointestinal symptoms in patients with type I diabetes.
Antroduodenal motility was recorded with an ambulatory manometric technique for a 20-h period, including a high-caloric high-fat dinner and a low-caloric low-fat breakfast and a long fasting period, after 2 weeks erythromycin and placebo treatment in 12 patients with type I diabetes. During the manometric study, plasma glucose concentrations were assessed by frequent self-testing. Gastrointestinal symptoms were scored daily to assess the severity of the symptoms (range 0-3).
Oral erythromycin decreased the migrating motor complex cycle length from 118.9 +/- 46.0 to 86.2 +/- 25.3 min (P = 0.03) by shortening phase II from 68.7 +/- 23.5 to 48.5 +/- 19.4 min (P < 0.05). The total number of duodenal phase III increased from 48 to 62 (P = 0.075). However, the degree of antral participation to duodenal phase III did not increase. Erythromycin significantly decreased the duration of the postprandial period after dinner (from 417.0 +/- 137.9 to 348.8 +/- 93.8 min, P = 0.04). During this shorter postprandial period, the number of antral contractions (P < 0.01) and the antral motility index increased (P < 0.03), and early phase III activity at the level of the duodenum was abolished. In diabetic patients with antral hypomotility, after dinner, the mean symptom score improved significantly, from 2.07 +/- 0.86 to 1.52 +/- 0.63 (P = 0.018).
This ambulatory antroduodenal manometric study showed that oral erythromycin (250 mg t.i.d.) improves both fasting and postprandial antroduodenal motor activity after a high-caloric meal in patients with type I diabetes. Furthermore, in diabetic subjects with postprandial antral hypomotility, erythromycin reduces dyspeptic symptoms.
Unlabelled:
Medium-chain triglycerides are known to induce diarrhea, possibly resulting from accelerated intestinal transit. We performed antroduodenal manometry and lactulose hydrogen breath testing simultaneously in eight healthy subjects in order to determine the effects of intraduodenally administered medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) on gastrointestinal motility and small bowel transit time. LCT (15 mmol/hr) induced a fed motor pattern. In contrast, during MCT, in both equimolar (15 mmol/hr; MCT-1) and equicaloric (30 mmol/hr; MCT-2) amounts comparable to LCT, interdigestive motility was preserved but with a significantly (P < 0.05) shorter MMC cycle length (MCT-1, 65 +/- 7 min; MCT-2, 53 +/- 6 min) compared to control (saline infusion; 127 +/- 14 min). Duodenocecal transit time (DCTT) was significantly (P < 0.05) accelerated during administration of MCT (MCT-1, 56 +/- 6 min; MCT-2, 69 +/- 9 min) and was not affected by LCT (105 +/- 13 min) when compared to control (101 +/- 9 min).
In conclusion:
MCT, in contrast to LCT, preserve interdigestive motility with a shorter MMC cycle length and accelerate DCTT.
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.
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.
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.
These results demonstrate the good tolerability and the favourable risk-benefit ratio of PCC for the treatment of functional dyspepsia.
The therapeutic equivalence of a fixed combination preparation consisting of peppermint oil and caraway oil (PCC, Enteroplant) and the prokinetic agent cisapride (CIS, CAS 81098-60-4) was investigated in a four-week randomized controlled double-blind study with planned adaptive interim analysis. The study comprised 120 outpatients with functional dyspepsia. The efficacy was evaluated in 118 patients. Of these, 60 patients received the enteric-coated combination preparation (2 x 1 capsule containing 90 mg peppermint oil +50 mg caraway oil per day) and 58 patients received the reference preparation cisapride (3 x 10 mg/day). The mean reduction of the pain score (primary variable) recorded on a visual analog scale (VAS) during the four-week treatment was 4.62 points with the peppermint oil/caraway oil preparation. This score was comparable with the mean reduction under cisapride (4.60 points) (p = 0.021; test for equivalence). Equivalence was also found in the secondary variable "frequency of pain" with a reduction by 4.65 points under PCC and by 4.16 points under cisapride carried out on an exploratory basis (p = 0.0034). Comparable results were attained with both treatments in the Dyspeptic Discomfort Score which included the other dyspeptic symptoms as well as intestinal and extraintestinal autonomic symptoms, in the prognosis as appraised by the physician and in the CGI scales (Clinical Global Impressions). Corresponding results were also found in Helicobacter pylori-positive patients and patients with initially intense epigastric pain in the two treatment groups. The combination preparation consisting of peppermint oil and caraway, oil appears to be comparable with cisapride and provides an effective means for treatment of functional dyspepsia. Both medications were tolerated well (adverse events were reported in 12 patients of the PCC group and in 14 patients of the CIS group).
The effect of peppermint oil on colonic motility in man
- Duthie HL