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Background: Gomphrena perennis L. is a native plant of South America whose pharmacological properties have not been studied yet. Aim: To evaluate the cardiovascular and intestinal pharmacological effects of Gomphrena perennis L. leaves tincture (GphT) and the mechanisms involved. Experimental procedure: The chromatographic profile of GphT was done. Its ex vivo effects were evaluated by contractile concentration-response curves (CRCs) obtained from the agonist carbachol or calcium found in isolated rat small intestine, as well as in the relaxant CRCs. Cardiac effects were evaluated on isolated rat hearts exposed to ischemia/reperfusion (I/R). Experiments in vivo were performed to evaluate the diuretic activity in conscious rats and the hypotensive effect in anaesthetised rats. Results: Fifteen flavonoids were identified in GphT by HPLC-UV, including diosmin. GphT induced a non-competitive inhibition in both carbachol and calcium CRCs on rat small intestine. The first was not affected by indomethacin. Moreover, GphT, unlike diosmin, relaxed the contracture produced by a high-potassium solution in a dose-dependently way. Neither propranolol nor l-NAME changed it. GphT did not show diuretic activity but induced hypotension insensitive to l-NAME. While GphT perfusion of isolated hearts increased injury consequent to I/R, oral administration was cardioprotective and reversed by l-NAME. However, diosmin did not improve the post-ischemic recovery. Conclusions: This study supports the use of Gomphrena perennis L. tincture as an antispasmodic and hypotensive agent. Moreover, it has been demonstrated to be preventive of post-ischemic cardiac dysfunction. However, diosmin would not be responsible for these effects.

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using plants has grown in significance in recent years. ZnO NPs were synthesized in this work via a chemical precipitation method with Jasminum sambac (JS) leaf extract serving as a capping agent. These NPs were characterized using UV-vis spectroscopy, FT-IR, XRD, SEM, TEM, TGA, and DTA. The results from UV-vis and FT-IR confirmed the band gap energies (3.37 eV and 3.50 eV) and the presence of the following functional groups: CN, OH, C=O, and NH. A spherical structure and an average grain size of 26 nm were confirmed via XRD. The size and surface morphology of the ZnO NPs were confirmed through the use of SEM analysis. According to the TEM images, the ZnO NPs had an average mean size of 26 nm and were spherical in shape. The TGA curve indicated that the weight loss starts at 100 °C, rising to 900 °C, as a result of the evaporation of water molecules. An exothermic peak was seen during the DTA analysis at 480 °C. Effective antibacterial activity was found at 7.32 ± 0.44 mm in Gram-positive bacteria (S. aureus) and at 15.54 ± 0.031 mm in Gram-negative (E. coli) bacteria against the ZnO NPs. Antispasmodic activity: the 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by (78.19%), acetylcholine (at a concentration of 1 µM) by (67.57%), and nicotine (at a concentration of 2 µg/mL) by (84.35%). The antipyretic activity was identified using the specific Shodhan vidhi method, and their anti-inflammatory properties were effectively evaluated with a denaturation test. A 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by 78.19%, acetylcholine (at a concentration of 1 µM) by 67.57%, and nicotine (at a concentration of 2 µg/mL) by 84.35%. These results underscore the sample solution's potential as an effective therapeutic agent, showcasing its notable antispasmodic activity. Among the administered doses, the 150 mg/kg sample dose exhibited the most potent antipyretic effects. The anti-inflammatory activity of the synthesized NPs showed a remarkable inhibition percentage of (97.14 ± 0.005) at higher concentrations (250 µg/mL). Furthermore, a cytotoxic effect was noted when the biologically synthesized ZnO NPs were introduced to treated cells. [ABSTRACT FROM AUTHOR]

Background and Aim: Functional dyspepsia (FD) remains a therapeutic challenge, and the efficacy of antispasmodic agents as adjunctive therapy is not well established. This study aimed to evaluate the efficacy and safety of pinaverium bromide added to omeprazole in treating refractory FD. Methods: We conducted a randomized, placebo‐controlled trial in patients with refractory dyspepsia. Participants were randomly assigned to receive pinaverium (50 mg, 3 times/day, n = 36) or placebo (n = 36) in addition to omeprazole for 8 weeks. The primary endpoint was the responder rate for adequate relief. Secondary outcomes included the Global Overall Symptom Scale (GOSS), quality of life, and safety profile. Results: No statistically significant differences were observed in the adequate relief response rate between the pinaverium bromide and control group at week 2 (58.3% vs. 62.9%, P = 0.697), week 4 (62.9% vs. 78.1%, P = 0.173), week 6 (64.7% vs. 75.0%, P = 0.363), and week 8 (64.7% vs. 75.0%, P = 0.363). Additionally, there were no significant differences observed in the decline of symptom score between the two groups at week 4 (8.4 ± 7.6 vs. 7.7 ± 7.1, P = 0.702) and week 8 (10.9 ± 8.2 vs. 8.4 ± 7.2, P = 0.196). Similarly, there were no significant differences in terms of quality of life between the two groups. Adverse event rates were also comparable between the two groups. Conclusion: Pinaverium bromide was found to be safe in the treatment of refractory dyspepsia, but it did not demonstrate a significant benefit in improving symptoms. [ABSTRACT FROM AUTHOR]

Acute gastrointestinal cramping pain (GICP) is a debilitating condition that affects many people worldwide, significantly reducing their quality of life. As such, prompt treatment is crucial. This article will explore relevant literature from databases such as PubMed, Scopus, Google Scholar, Cochrane Library, and Web of Science. Additionally, we searched ClinicalTrials.gov and the WHO ICTRP database for the latest clinical trials. Consensus dictates that antispasmodics such as hyoscine-N-butyl bromide and mebeverine should be the primary treatment for GICP. If these prove ineffective, patients can switch to an antispasmodic with a different mode of action or add acetaminophen/NSAIDs for more severe cases. Currently, several antispasmodics are undergoing clinical trials, including drotaverine, alverine, pinaverium, otilonium bromide, fenoverine, tiropramide, otilonium bromide, trimebutine, and peppermint oil. Well-designed head-to-head studies are necessary to evaluate current antispasmodics' safety, efficacy, pharmacokinetic, and pharmacoeconomics profiles. Recent studies have shown that fixed-dose combinations of antispasmodics + NSAIDs or two different antispasmodics can improve patient compliance and synergistically reduce GICP. Therefore, it is recommended that the global availability and accessibility of these products be enhanced. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Functional dyspepsia (FD) remains a therapeutic challenge, and the efficacy of antispasmodic agents as adjunctive therapy is not well established. This study aimed to evaluate the efficacy and safety of pinaverium bromide added to omeprazole in treating refractory FD. Methods We conducted a randomized, placebo‐controlled trial in patients with refractory dyspepsia. Participants were randomly assigned to receive pinaverium (50 mg, 3 times/day, n = 36) or placebo (n = 36) in addition to omeprazole for 8 weeks. The primary endpoint was the responder rate for adequate relief. Secondary outcomes included the Global Overall Symptom Scale (GOSS), quality of life, and safety profile. Results No statistically significant differences were observed in the adequate relief response rate between the pinaverium bromide and control group at week 2 (58.3% vs. 62.9%, P = 0.697), week 4 (62.9% vs. 78.1%, P = 0.173), week 6 (64.7% vs. 75.0%, P = 0.363), and week 8 (64.7% vs. 75.0%, P = 0.363). Additionally, there were no significant differences observed in the decline of symptom score between the two groups at week 4 (8.4 ± 7.6 vs. 7.7 ± 7.1, P = 0.702) and week 8 (10.9 ± 8.2 vs. 8.4 ± 7.2, P = 0.196). Similarly, there were no significant differences in terms of quality of life between the two groups. Adverse event rates were also comparable between the two groups. Conclusion Pinaverium bromide was found to be safe in the treatment of refractory dyspepsia, but it did not demonstrate a significant benefit in improving symptoms.

Background: Gastrointestinal problems are among the most common diseases in Morocco people, who frequently use aromatic and medicinal plants to eliminate these problems. Thymus algeriensis is one of these plants widely used to treat gastrointestinal problems. This research aimed to identify the phytochemical compounds present in Thymus algeriensis essential oil (TaEO), assess its acute toxicity, and investigate its potential myorelaxant and antispasmodic effects. Methods: In vitro experiments were conducted on rat and rabbit jejunum using an isotonic transducer and in silico docking calculations were conducted on l-type voltage-gated Ca2+and muscarinic receptor active sites. Results: The GC–MS analysis of TaEO revealed the presence of 11 compounds, with 89.77 % of the compounds identified being oxygenated monoterpenes, among which Thujone dominates the composition with 32.89 %. The administration of TaEO did not produce any observable signs of toxicity or mortality at 1 g/Kg.bw. TaEO exhibit a dose-dependent decrease in the basal contractions of the rabbit jejunum with an IC50 value of 5.66 ± 1.88 µg/mL. In addition, TaEO induced an antispasmodic effect on KCl and CCh-induced contractions in the rat jejunum. The inhibitory effect demonstrated are similar to those produced by a non-competitive antagonist of voltage-dependent calcium channel and cholinergic receptors. These results are boosted by the docking study when we showed that Thujone could bind to the active site of muscarinic receptor and, l-type voltage-gated Ca2+ with a binding energy equal to -59.401 and, -47.441 Kcal/mol respectively. Conclusions: These results provide strong confirmation for the traditional use of Thymus algeriensis in Moroccan as an effective antispasmodic remedy and give a new lead to find a phytomedicament against gastrointestinal problems.

Irritable bowel syndrome (IBS) is a common longstanding condition with a variety of symptoms including constipation, diarrhoea and abdominal cramps or bloating. There are no specific causes of IBS; therefore, symptoms and management are individualised to each patient. Management strategies involve lifestyle advice on diet and exercise, medications and psychological therapies. IBS can be extremely debilitating to patients' quality of life and is usually diagnosed as a process of elimination of other gastrointestinal conditions that can have similar symptoms, such as inflammatory bowel disease. Medications to manage IBS include laxatives, antispasmodics, antimotility agents and neuromodulators, as IBS is believed to be a disorder of the gut--brain axis. [ABSTRACT FROM AUTHOR]

Digestive disorders are common reasons for medical consultations, making natural remedies based on medicinal plants increasingly popular. This study explored the potential benefits of Thymus algeriensis on the motility of the smooth intestinal muscle to address digestive tract disorders. The study focused on an in vitro test using the rat jejunum to evaluate the antispasmodic and relaxant effects of its dichloromethane fraction. The results showed that the dichloromethane fraction caused a significant relaxing effect on spontaneous contraction and an antispasmodic effect on rat jejunum precontracted with carbachol or KCl in a dose-response manner (p ˂ 0.001). The inhibitory activity demonstrated was comparable to those produced by a non-competitive antagonist of voltage-dependent Calcium channel and cholinergic receptors. These findings highlight the potential of Thymus algeriensis dichloromethane fraction to address digestive disorders. [ABSTRACT FROM AUTHOR]

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using plants has grown in significance in recent years. ZnO NPs were synthesized in this work via a chemical precipitation method with Jasminum sambac (JS) leaf extract serving as a capping agent. These NPs were characterized using UV-vis spectroscopy, FT-IR, XRD, SEM, TEM, TGA, and DTA. The results from UV-vis and FT-IR confirmed the band gap energies (3.37 eV and 3.50 eV) and the presence of the following functional groups: CN, OH, C=O, and NH. A spherical structure and an average grain size of 26 nm were confirmed via XRD. The size and surface morphology of the ZnO NPs were confirmed through the use of SEM analysis. According to the TEM images, the ZnO NPs had an average mean size of 26 nm and were spherical in shape. The TGA curve indicated that the weight loss starts at 100 °C, rising to 900 °C, as a result of the evaporation of water molecules. An exothermic peak was seen during the DTA analysis at 480 °C. Effective antibacterial activity was found at 7.32 ± 0.44 mm in Gram-positive bacteria (S. aureus) and at 15.54 ± 0.031 mm in Gram-negative (E. coli) bacteria against the ZnO NPs. Antispasmodic activity: the 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by (78.19%), acetylcholine (at a concentration of 1 µM) by (67.57%), and nicotine (at a concentration of 2 µg/mL) by (84.35%). The antipyretic activity was identified using the specific Shodhan vidhi method, and their anti-inflammatory properties were effectively evaluated with a denaturation test. A 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by 78.19%, acetylcholine (at a concentration of 1 µM) by 67.57%, and nicotine (at a concentration of 2 µg/mL) by 84.35%. These results underscore the sample solution’s potential as an effective therapeutic agent, showcasing its notable antispasmodic activity. Among the administered doses, the 150 mg/kg sample dose exhibited the most potent antipyretic effects. The anti-inflammatory activity of the synthesized NPs showed a remarkable inhibition percentage of (97.14 ± 0.005) at higher concentrations (250 µg/mL). Furthermore, a cytotoxic effect was noted when the biologically synthesized ZnO NPs were introduced to treated cells.

Background: The leaves of Origanum majorana (O. majorana) are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract. Methods: Gas chromatography–mass spectrometry (GC-MS) was used to identify the phytochemicals, and Swiss albino mice were used for an in vivo antidiarrheal assay. Isolated rat ileum was used as an ex vivo assay model to study the possible antispasmodic effect and its mechanism(s). Results: The GC-MS analysis of O. majorana detected the presence of 21 compounds, of which alpha-terpineol was a major constituent. In the antidiarrheal experiment, O. majorana showed a substantial inhibitory effect on diarrheal episodes in mice at an oral dosage of 200 mg/kg, resulting in 40% protection. Furthermore, an oral dosage of 400 mg/kg provided even greater protection, with 80% effectiveness. Similarly, loperamide showed 100% protection at oral doses of 10 mg/kg. O. majorana caused complete inhibition of carbachol (CCh, 1 µM) and high K+ (80 mM)-evoked spasms in isolated ileal tissues by expressing significantly higher potency (p < 0.05) against high K+ compared to CCh, similar to verapamil, a Ca++ antagonist. The verapamil-like predominant Ca++ ion inhibitory action of O. majorana was further confirmed in the ileal tissues that were made Ca++-free by incubating the tissues in a physiological salt solution having ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The preincubation of O. majorana at increasing concentrations (0.3 and 1 mg/mL) shifted towards the right of the CaCl2-mediated concentration-response curves (CRCs) with suppression of the maximum contraction. Similarly, verapamil also caused non-specific suppression of Ca++ CRCs towards the right, as expected. Conclusions: Thus, this study conducted an analysis to determine the chemical constituents of the leaf extract of O. majorana and provided a detailed mechanistic basis for the medicinal use of O. majorana in hyperactive gut motility disorders.

Satureja montana L. (SM) has a long traditional use as a spice and a medicine for various gastrointestinal disorders, including painful spasms and diarrhea. Contrary to conventional drugs, administration of SM and its extracts are considered safe. Previous studies have shown that the essential oils (EOs) of SM from different areas are rich in monoterpenes, sesquiterpenes, diterpens, and phenolic compounds, including flavonoids, tannins, and acids with great composition variability. Determination of composition of EO from Herzegovinian SM done by gas chromatographyflame ionization detection and gas chromatography mass spectrometry (GC-FID and GC/MS, respectively) revealed carvacrol as a primary substance followed by γ-terpinene, p-cymene, and ß-caryophyllene. Ex vivo spasmolitic activity caused by EO was evident in different types of isolated rat ileum function with the most potent effect on spontaneous activity followed by electrical field stimulation and KCl- and CaCl2-induced activity. SMEO produced in vivo antidiarreal activity on castor oil-induced diarrhea in young rats and showed the potential to cause a decrese water content in the feces of adult Wistar rats. This study indicates that effects of SM on the intestinum could be mediated through combination of Kv channel activation and Ca channel blockade, but additional mechanisms might be involved. The results of this study corroborate the traditional use of SM as antispasmodic, antidiarrheal, and antisecretory agents. [ABSTRACT FROM AUTHOR]

Polystichum lonchitis L. is a fern belonging to the family Dryopteridaceae. The present study was conducted to evaluate its pharmacological, antioxidant, and phytochemical properties, and to conduct GC–MS screening of P. lonchitis. The acetic acid-induced writhing test, yeast-induced hyperpyrexia method, carrageenan-induced rat paw edema model, and charcoal meal test model were carried out to assess analgesic, antipyretic, anti-inflammatory, and antispasmodic activity, respectively. DPPH was used as an antioxidant, while the phytochemical screening was conducted using standard scientific methods. Among the pharmacological activities, the most significant effects were observed in the analgesic and anti-inflammatory activities, followed by the antipyretic and antispasmodic activities, at a dose of 450 mg/kg after the 4th hour, compared with 150 mg/kg and 300 mg/kg. For the evaluation of antioxidant activities, the most significant results were detected in the methanolic and aqueous extracts. The detection of flavonoids and phenol occurred most significantly in the methanolic extract, and then in the ethanolic and aqueous extracts. The main compounds detected using GC–MS analysis with a high metabolic rate was -D-Galactopyranoside, which had a metabolic rate of 0.851, and methyl and n-hexadecanoic, which had a metabolic rate of 0.972. Overall, the results suggested that P. lonchitis had a strong potential for pharmacological activities. The suggested assessment provided a way to isolate the bioactive constituents and will help to provide new medicines with fewer side effects. Due to the fern's effectiveness against various diseases, the results provide clear evidence that they also have the potential to cure various diseases. [ABSTRACT FROM AUTHOR]

The present work examined the in vivo antispasmodic and nephroprotective potentials of methanolic extracts obtained from Algerian native propolis and bee pollen. The in vivo antispasmodic activity was assessed by the intraperitoneal injection of acetic acid (1%) which induced long-lasting visceral pain in mice. The renal damage was modelled by intraperitoneal injection of a cisplatin (CP; 10 mg/kg) followed by histopathological changes in kidneys. In addition, the beehive by-products were screened for their bioactive content and in vitro antioxidant activities. The propolis and bee pollen are rich sources of bioactive compounds. The propolis showed the highest antioxidant potencies as evaluated by β-carotene bleaching system (87.16 ± 3.69%), DPPH (176.05 ± 0.20 μg/mL), and FRAP (0.61 ± 0.002 μmol Fe(II)/g) assays. The antispasmodic test revealed that propolis extract (250 mg/kg) significantly inhibited the number of spasms (61.04 ± 3.92%) induced by acetic acid. Based on histopathology examinations, bee pollen extract at 250 mg/kg significantly reduced nephrotoxic effects induced by CP injection. These results provided a good scientific basis for future research on antispasmodic and nephroprotective effects and/or mechanisms of propolis and bee pollen, which confer them a real application in drug discovery. [ABSTRACT FROM AUTHOR]

Background: Medicinal herbs are frequently used for the management of gastrointestinal disorders because they contain various compounds that can potentially amplify the intended therapeutic effects. Cuminaldehyde is a plant-based constituent found in oils derived from botanicals such as cumin, eucalyptus, myrrh, and cassia and is responsible for its health benefits. Despite the utilization of cuminaldehyde for several medicinal properties, there is currently insufficient scientific evidence to support its effectiveness in treating diarrhea. Hence, the present investigation was carried out to evaluate the antidiarrheal and antispasmodic efficacy of cuminaldehyde, with detailed pharmacodynamics explored. Methods: An in vivo antidiarrheal test was conducted in mice following the castor oil-induced diarrhea model, while an isolated small intestine obtained from rats was used to evaluate the detailed mechanism(s) of antispasmodic effects. Results: Cuminaldehyde, at 10 and 20 mg/kg, exhibited 60 and 80% protection in mice from episodic diarrhea compared to the saline control group, whereas this inhibitory effect was significantly reversed in the pretreated mice with glibenclamide, similar to cromakalim, an ATP-dependent K+ channel opener. In the ex vivo experiments conducted in isolated rat tissues, cuminaldehyde reversed the glibenclamide-sensitive low K+ (25 mM)-mediated contractions at significantly higher potency compared to its inhibitory effect against high K+ (80 mM), thus showing predominant involvement of ATP-dependent K+ activation followed by Ca++ channel inhibition. Cromakalim, a standard drug, selectively suppressed the glibenclamide-sensitive low K+-induced contractions, whereas no relaxation was observed against high K+, as expected. Verapamil, a Ca++ channel inhibitor, effectively suppressed both low and high K+-induced contractions with similar potency, as anticipated. At higher concentrations, the inhibitory effect of cuminaldehyde against Ca++ channels was further confirmed when the preincubated ileum tissues with cuminaldehyde (3 and 10 mM) in Ca++ free medium shifted CaCl2-mediated concentration-response curves (CRCs) towards the right with suppression of the maximum peaks, similar to verapamil, a standard Ca++ ion inhibitor. Conclusions: Present findings support the antidiarrheal and antispasmodic potential of cuminaldehyde, possibly by the predominant activation of ATP-dependent K+ channels followed by voltage-gated Ca++ inhibition. However, further in-depth assays are recommended to know the precise mechanism and to elucidate additional unexplored mechanism(s) if involved.

Platanus orientalis is traditionally used to treat diarrhea and spasm. However, studies are lacking on its mechanism of action in diarrhea and spasm. Pharmacological in-vivo activities were performed. In-vitro activities were carried out to explore the underlying mechanism(s) of action in isolated tissue preparations of mice jejunum and ileum. Crude extract of Platanus orientalis, loperamide and verapamil were used. The crude extract provided dose-dependent protection in castor oil diarrhea like verapamil and reduced the intestinal fluid accumulation and charcoal meal transit distance. In-vitro studies produced spasmolytic effect on the spontaneous (EC50 value=0.21mg/mL), high K+ (EC50 value=0.37mg/mL) and carbachol (CCh)-induced contractions 5.35mg/mL (3.88-6.85) respectively. The quiescent ileum responded well to the high K+ and carbachol (CCh)-induced contractions when tested against crude extract. It caused inhibition of the induced contraction with EC50 values of 0.20mg/mL (0.10-0.30) and 3.25mg/mL (2-4.5) respectively and showed potent effect against CCh-induced contractions. Calcium response curves produced a similar effect to verapamil. The crude extract of Platanus orientalis remained safe up to 5g/kg dose. [ABSTRACT FROM AUTHOR]

Background and Aim: Colonoscopy quality, including lesion detectability, is variable, and factors influencing lesion detection are not fully understood. This study investigated lesion detection rates during colonoscopies and the associated factors in the SCREEning of Swedish COlons (SCREESCO) study. Methods: In this cross‐sectional analysis of data from SCREESCO, a large‐scale randomized controlled trial of colorectal cancer screening in the Swedish population aged 60 years, we assessed data of first‐time colonoscopies performed in both colonoscopy and fecal immunochemical test (FIT) arms. Results: This study included 16 552 individuals. The adenoma detection rate was 23.9% and 37.8% in colonoscopy and FIT arms, respectively. Regarding colonoscopy procedures, a withdrawal time ≥ 6 min was associated with higher detection rates of advanced adenomas (adjusted odds ratio [AOR] 2.474, 95% confidence interval [CI] 1.295–4.723), adenomas (2.181, 1.515–3.140), and proximal serrated lesions (pSLs) (1.713, 1.007–2.915). Antispasmodic use was associated with higher detection rates of these lesions and sessile serrated lesions (SSLs) (AOR, 95% CI: 1.523, 1.295–1.791; 1.361, 1.217–1.522; 1.450, 1.247–1.687; and 1.810, 1.512–2.167, respectively). Insertion time > 20 min was related to lower detection rates of adenomas, pSLs, and SSLs (AOR, 95% CI: 0.753, 0.639–0.887; 0.640, 0.495–0.828; and 0.704, 0.518–0.955, respectively). The relationship between a recent period and higher detection rates of pSLs and SSLs was also demonstrated. Conclusion: Lesion detectability in SCREESCO was mostly acceptable with room for improvement. In addition to sufficient withdrawal time, antispasmodic use and acquiring skills enabling short insertion time may improve lesion detection. Trial registration: ClinicalTrials.gov, ID: NCT02078804. [ABSTRACT FROM AUTHOR]

Thyme (Thymus vulgaris L.) is a well-known medicinal plant, the aerial parts of which have long been used internally or externally as a traditional remedy for various diseases. Thyme essential oils have important pharmaceutical applications and are regularly used in the pharmaceutical, food and cosmetic industries. In folk medicine, thyme preparations are used to treat respiratory, digestive, cardiovascular and nervous disorders, as well as to relieve dysmenorrhea. Thymol, a major constituent of Thymus vulgaris essential oil, has been shown to affect skeletal and smooth muscle excitation and contraction. Therefore, the main objective of this study was to evaluate its effect on acetylcholine (ACh)-induced rat intestinal and uterine preparations. Isolated ileum and uterine horn preparations were placed in a 20-ml organ bath containing Tyrode or De Jalon solution and exposed to graded concentrations of ACh (0.036, 0.109, 0.36, 1.09, 3,6, 10.9, and 36 µM) and either 0.02 or 0.2 mM thymol. Additionally, the dose-response relationship of thymol impact on intestinal and uterine contraction was evaluated. Contraction changes were monitored using an isometric transducer. Thymol at the higher dose (0.2 mM) significantly reduced ACh-induced intestinal and uterine contractions. Thus, this study provides new important data on competitive actions between thymol and ACh. In the dose-response study, the IC50 values were calculated as 5.26 mM for the ileum and 5.35mM for the uterus. Our results demonstrated the efficacy of thymol in reducing ileal and uterine smooth muscle contractions, thus supporting the use of thyme in traditional medicine in the treatment of digestive disorders and painful menstrual cramps. [ABSTRACT FROM AUTHOR]

Extracts from Drosera rotundifolia are traditionally used to treat cough symptoms during a common cold. The present study aimed to investigate the impact of extracts from D. rotundifolia and active compounds on the respiratory tract. Tracheal slices of C57BL/6N mice were used ex vivo to examine effects on airway smooth muscle (ASM) and ciliary beat frequency (CBF). Phosphodiesterase (PDE) inhibition assays were carried out to test whether PDE1 or PDE4 are targeted by the active compounds. An ethanol–water extract, as well as an aqueous fraction of this extract, exerted antispasmodic properties against acetylcholine-induced contractions. In addition, contractions induced by 60 mM K+ were abrogated by the aqueous fraction. Effects on ASM could be attributed to the flavonoids quercetin, 2″-O-galloylhyperoside and hyperoside. Moreover, the Drosera extract and the aqueous fraction increased the CBF of murine tracheal slices. Quercetin and 2″-O-galloylhyperoside were identified as active compounds involved in the elevation of CBF. Both compounds inhibited PDE1A and PDE4D. The elevation of CBF was mimicked by the subtype-selective PDE inhibitor rolipram (PDE4) and by 8-methoxymethyl-IBMX. In summary, our study shows, for the first time, that a Drosera extract and its flavonoid compounds increase the CBF of murine airways while antispasmodic effects were transferred to ASM. [ABSTRACT FROM AUTHOR]

The current study aimed to assess the pharmacological potential of Justicia adhatoda by evaluating the presence of biologically active compounds using the gas chromatography-mass spectrometry approach and to undertake biological activities for the effectiveness of the present compounds using standard tests. A total of 21 compounds were identified in the gas chromatography-mass spectrometry analysis of the ethyl acetate fraction in which 14 of the identified compounds are recognized for their pharmacological potential in the literature. In total, four fractions (ethyl acetate, chloroform, n-hexane, and aqueous) were evaluated for pharmacological activities. In carrageenan-induced inflammation, the chloroform fraction exhibited high anti-inflammatory activity (46.51%). Similarly, the analgesic potential of ethyl acetate fraction was the most effective (300 mg/kg) in the acetic acid-induced test. Similarly, in the formalin test, ethyl acetate fraction exhibited maximum inhibition in both early (74.35%) and late phases (88.38). Maximum inhibition of pyrexia (77.98%) was recorded for the ethyl acetate fraction (300 mg/kg). In DPPH assay, the ethyl acetate fraction revealed the highest scavenging potential among other fractions (50 µg/ml resulted in 50.40% and 100 µg/ml resulted in 66.74% scavenging). [ABSTRACT FROM AUTHOR]

Context: Warionia saharae Benthem ex Benth. & Coss has been widely used for gastrointestinal problems in Morocco and Algeria. Aims: To explore the possible mechanism for its use to such ailments in order to rationalize some of these folkloric uses. We investigated the aqueous extract of this plant (AqWs) for antispasmodic activity on isolated rat and rabbit jejunums. Methods: To investigate the contractile activity of isolated jejunum preparations of rat and rabbit we had used in vitro techniques. Jejunums were suspended in tissue baths filled with KHB culture medium (37°C) and connected to force transducers. AqWs (0.1–3 mg/mL) was used with or without carbachol (10-6 M), KCl (25 mM), yohimbine (10-5 M), prazosin (10-5 M), propranolol (10-5 M), hexamethonium (10-4 M), atropine (10-6 M), methylene blue (10-5 M), L-NAME (10-4 M) and nifedipine (10-6 M). Results: AqWs at 0.1–3 mg/mL produced a relaxation on basal rabbit contractions with an IC50 = 1.55 ± 0.06 mg/mL. This effect was reversible and was not affected by pretreatment with the inhibitors of α and β adrenergic receptors yohimbine, prazosin and propranolol. The extract had an antispasmodic activity with an IC50 = 1.25 ± 0.02 mg/mL on rat jejunum precontracted with KCl rich medium (25 mM). This result suggests that the extract had a Ca2+ antagonist effect. This was fortified when pretreatment of the intestine with the extract induced a rightward shift in the Ca2+ concentration-response curves. AqWs exhibited also antispasmodic effect on carbachol (10-6 M)-induced contractions of rat jejunums with an IC50 = 1.53 ± 0.04 mg/mL. The extract at 3 mg/mL on rat jejunums pre-incubated with hexamethonium (10-4 M), atropine (10-6 M), and methylene blue (10-5 M), then contracted by KCl, decreased the maximum contraction but not totally like KCL alone without these inhibitors. For the jejunum pre-incubated with L-NAME (10-4 M), the spasmolytic effect of AqWs was comparable with KCL. Conclusions: These results suggest that the myorelaxant and antispasmodic effects are mediated possibly via Ca2+ antagonist, anticholinergic, and guanylate cyclase mechanisms but not by adrenergic and nitric oxide pathway.

Thyme (Thymus vulgaris L.) is a well-known medicinal plant, the aerial parts of which have long been used internally or externally as a traditional remedy for various diseases. Thyme essential oils have important pharmaceutical applications and are regularly used in the pharmaceutical, food and cosmetic industries. In folk medicine, thyme preparations are used to treat respiratory, digestive, cardiovascular and nervous disorders, as well as to relieve dysmenorrhea. Thymol, a major constituent of Thymus vulgaris essential oil, has been shown to affect skeletal and smooth muscle excitation and contraction. Therefore, the main objective of this study was to evaluate its effect on acetylcholine (ACh)-induced rat intestinal and uterine preparations. Isolated ileum and uterine horn preparations were placed in a 20-ml organ bath containing Tyrode or De Jalon solution and exposed to graded concentrations of ACh (0.036, 0.109, 0.36, 1.09, 3,6, 10.9, and 36 μM) and either 0.02 or 0.2 mM thymol. Additionally, the dose–response relationship of thymol impact on intestinal and uterine contraction was evaluated. Contraction changes were monitored using an isometric transducer. Thymol at the higher dose (0.2 mM) significantly reduced ACh-induced intestinal and uterine contractions. Thus, this study provides new important data on competitive actions between thymol and ACh. In the dose–response study, the IC50 values were calculated as 5.26 mM for the ileum and 5.35 mM for the uterus. Our results demonstrated the efficacy of thymol in reducing ileal and uterine smooth muscle contractions, thus supporting the use of thyme in traditional medicine in the treatment of digestive disorders and painful menstrual cramps.

The current study aimed to assess the pharmacological potential of Justicia adhatoda by evaluating the presence of biologically active compounds using the gas chromatography–mass spectrometry approach and to undertake biological activities for the effectiveness of the present compounds using standard tests. A total of 21 compounds were identified in the gas chromatography–mass spectrometry analysis of the ethyl acetate fraction in which 14 of the identified compounds are recognized for their pharmacological potential in the literature. In total, four fractions (ethyl acetate, chloroform, n-hexane, and aqueous) were evaluated for pharmacological activities. In carrageenan-induced inflammation, the chloroform fraction exhibited high anti-inflammatory activity (46.51%). Similarly, the analgesic potential of ethyl acetate fraction was the most effective (300 mg/kg) in the acetic acid-induced test. Similarly, in the formalin test, ethyl acetate fraction exhibited maximum inhibition in both early (74.35%) and late phases (88.38). Maximum inhibition of pyrexia (77.98%) was recorded for the ethyl acetate fraction (300 mg/kg). In DPPH assay, the ethyl acetate fraction revealed the highest scavenging potential among other fractions (50 μg/ml resulted in 50.40% and 100 μg/ml resulted in 66.74% scavenging).

Irritable bowel syndrome (IBS) is a common disorder of gut–brain interaction associated with significant disease burden. This American Gastroenterological Association guideline is intended to support practitioners in decisions about the use of medications for the pharmacological management of IBS-C and is an update of a prior technical review and guideline. The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The technical review panel prioritized clinical questions and outcomes according to their importance for clinicians and patients and conducted an evidence review of the following agents: tenapanor, plecanatide, linaclotide, tegaserod, lubiprostone, polyethylene glycol laxatives, tricyclic antidepressants, selective serotonin reuptake inhibitors, and antispasmodics. The Guideline Panel reviewed the evidence and used the Evidence-to-Decision Framework to develop recommendations. The panel agreed on 9 recommendations for the management of patients with IBS-C. The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty). [ABSTRACT FROM AUTHOR]

(1) Background: Ocimum basilicum L. is an aromatic medicinal plant of the Lamiaceae family known as sweet basil. It is used in traditional medicine for its beneficial effects on gastrointestinal disorders, inflammation, immune system, pyrexia or cancer among others. Ocimum basilicum (OB) leaf extracts contain many phytochemicals bearing the plant health effects but no reports is available on the potential bioactivity of stem extracts. Our investigation aimed at assessing the differential biological activity between basil leaf and stem to promote this co-product valorization. (2) Method: For this purpose we explored phytochemical composition of both parts of the plant. Antioxidant activity was evaluated through total polyphenol content measure, DPPH and ORAC tests. Anti-inflammatory markers on stimulated macrophages, including NO (nitric oxide), TNFa (tumor necrosis factor alpha), IL-6 (interleukin 6), MCP1 (monocyte attractant protein 1) and PGE-2 (prostaglandin E2), were evaluated. In addition, we investigated OB effects on jejunum smooth muscle contractility. (3) Results: OB extracts from leaves and stems demonstrated a different biological activity profile at the level of both antioxidant, anti-inflammatory and smooth muscle relaxation effects. (4) Conclusion: Taken together our results suggest that Ocimum basilicum extracts from co-product stems, in addition to leaves, may be of interest at the nutrition-health level with specific therapeutic potential. [ABSTRACT FROM AUTHOR]

The present study attempted to evaluate and rationalize the medicinal use of the methanolic extract of the fruits of Balanites aegyptiaca (B. aegyptiaca) in the treatment of hyperactive gut disorders. The in vivo, castor oil-induced diarrhea model in mice was followed to test its antidiarrheal effect. To test the antispasmodic effect and to explore its pharmacodynamic details, isolated small intestines (ileum) obtained from rats were selected to provide physiological conditions for the ex vivo assays. In the in vivo assays, the orally administered extract of B. aegyptiaca protected mice from diarrheal drops with resultant percent inhibitions of 40% and 80% at the respective doses of 200 mg/kg and 400 mg/kg, while the highest protection (100%) was observed with a positive control drug, loperamide, at 10 mg/kg. In the ileum, B. aegyptiaca produced an antispasmodic effect in a concentration-dependent manner by inhibiting the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms with resultant EC50 values of 1.44 mg/mL (1.08–1.78) and 1.27 mg/mL (0.98–1.66), respectively. Papaverine, a known phosphodiesterase enzyme (PDE) inhibitor and blocker of Ca++ channels (CCB), also inhibited both CCh and high K+ induced contractions at comparable EC50 values of 8.72 µM (7.92–9.24) and 8.14 µM (7.62–8.84), respectively. Contrary to the extract and papaverine, verapamil showed distinctly higher potency in regard to inhibiting high K+, compared to CCh-evoked spasms that had EC50 values of 0.16 µM (0.13–0.261) and 2.54 µM (2.28–2.92), respectively. The inhibitory effects of B. aegyptiaca on PDE were further confirmed when the pre-incubated extract shifted the isoprenaline-mediated relaxation curves (CRCs) towards the left, similar to papaverine, whereas the CCB-like effect was confirmed when the pre-incubated tissues with B. aegyptiaca caused deflection in the Ca++ CRCs towards the right, constructed in Ca++ free medium with suppression of the maximum response. Thus, this study provides detailed, mechanistic support for the medicinal use of B. aegyptiaca in the treatment of hyperactive gut disorders. [ABSTRACT FROM AUTHOR]

Apart from the nutritional value, Cucumis sativus L. has also been used in the traditional medicine of Iran, Pakistan, and India. Its seeds are used by herbalists to treat gastrointestinal, respiratory, and urinary problems. However, more investigations are required to explain its mechanisms for treating GI, respiratory, and urinary diseases. Accordingly, the aim of the present work was to investigate the antispasmodic, bronchodilator, and antidiarrheal activities of C. sativus seeds extracts and the underlying mechanisms of action. For this purpose, sequential extracts of C. sativus seeds were prepared in n-hexane, dichloromethane, ethanol, and water. Bioactive compounds in C. sativus seed extracts were identified and quantified by utilizing LC ESI–MS/MS and HPLC. Moreover, network pharmacology and molecular docking were employed to examine the antispasmodic and bronchodilator effects of the bioactive substances in the extracts. In vitro and in vivo experiments were also conducted to validate the mechanistic insights gained from the in silico analysis. Results indicated the presence of kaempferol with a concentration of 813.74 µg/g (highest concentration) in the seed extract of C. sativus, followed by quercetin (713.83 µg/g), narcissin (681.87 µg/g), and orientin (676.19 µg/g). In silico investigations demonstrated that the bioactive chemicals in C. sativus seeds inhibited the expression of the target genes involved in smooth muscle contraction and calcium-mediated signaling. Sequential seed extracts of C. sativus caused a dose-dependent relaxant response for spasmolytic reaction and resulted in a relaxation of K+ (80 mM) spastic contraction. In animal models, C. sativus seed extracts exhibited partial or complete antiperistalsis, antidiarrheal, and antisecretory actions. By modulating the contractile response through calcium-mediated signaling target proteins, C. sativus seeds generated bronchodilator, antispasmodic, and antidiarrheal therapeutic effects. [ABSTRACT FROM AUTHOR]

Purpose: To compare 5 different rectal preparation strategies for prostate MRI. Methods: This 5-arm quality-assurance study evaluated 56 patients per arm (280 patients) including: no preparation, clear-fluids diet (CFD) beginning at 00:00 hours on the day of MRI, Fleet®-enema, enema + CFD, enema + CFD + IV-antispasmodic agent. The study was powered to 0.80 with alpha-error of 0.05. Three blinded radiologists independently evaluated T2-Weighted (T2W) and Diffusion Weighed Imaging (DWI) for: rectal diameter (maximal AP diameter), rectal content (stool, fluid, gas), rectal motion, T2W/DWI image quality, T2W image sharpness and DWI susceptibility artifact using 5-point Likert scales. Overall comparisons were performed using analysis of variance (ANOVA) and Kruskal-Wallis, with pair-wise comparisons using paired t-tests and Wilcoxon sign-rank tests. Results: Rectal diameter and amount of gas were lower in enema compared to non-enema groups (p < 0.001), with smallest diameter and least gas in the enema + CFD + IV-antispasmodic group (p = 0.022-<0.001). T2W image quality and sharpness were highest in the enema + CFD groups (p < 0.001) with no difference comparing enema + CFD with/without IV-antispasmodic (p = 0.064, 0.084). Motion artifact was least in enema + CFD + IV-antispasmodic group compared to all other groups (p < 0.001), followed by the enema + CFD group (p = 0.008-<0.001). DWI image quality was highest (p < 0.001) and DWI susceptibility artifact lowest (p < 0.001) in the enema + CFD groups (p < 0.001) and did not differ comparing enema + CFD with/without anti-spasmodic (p = 0.058-0.202). Conclusions: Use of enema + clear-fluids diet before prostate MRI yields the highest T2W and DWI image quality with the least DWI artifact. IV-antispasmodic use reduces motion on T2W but does not improve image quality on T2W or DWI, or lessen DWI artifact compared to enema + clear-fluids diet. [ABSTRACT FROM AUTHOR]

Hyoscine butylbromide (HBB) is one of the most used antispasmodics in clinical practice. Recent translational consensus has demonstrated a similarity between human colonic motor patterns studied ex vivo and in vivo, suggesting ex vi vo can predict in vivo results. It is unclear whether the mechanism of action of antispasmodics can predict different use in clinical practice. The aim of the present study is to bridge this gap dissecting HBB's role in excitatory and inhibitory neural pathways. Methods: 309 colon samples from 48 patients were studied in muscle bath experiments. HBB was tested on: 1-spontaneous phasic contractions (SPCs); 2-carbachol-induced contractility; electrical field stimulation (EFS)-induced selective stimulation of 3-excitatory and 4-inhibitory pathways and 5- SPCs and EFS-induced contractions enhanced by neostigmine. Atropine, AF-DX116 (M2 blocker) and DAU-5884 (M3 blocker) were used as comparators. In the presence of tetrodotoxin (TTX), HBB and atropine 1 μM reduced SPCs. HBB and atropine concentration-dependently reduced carbachol- and EFS-induced contractions. Inhibitory effects of DAU-5884 on EFS-induced contractions were more potent than of AF-DX116. HBB did not affect the off-response associated to neural inhibitory responses. Neostigmine enhanced both SPCs and EFS-induced contractions. In the presence of TTX and ω-conotoxin (GVIA), neostigmine still enhanced SPCs. Addition of HBB and atropine reduced these responses. This study demonstrates that HBB inhibits neural cholinergic contractions associated to muscarinic (mainly M3) receptors. HBB has a potential role in reducing colonic spasm induced by the release of acetylcholine from enteric motor neurons and from an atypical source including a potential non-neuronal origin. • Hyoscine Butylbromide (HBB) reduced colonic contractions. • The receptor involved in the response is mainly the M3 muscarinic receptor. • Neural-mediated relaxation and its off-contraction were unaffected by HBB. • After neural blockade, HBB reduced contractions enhanced with neostigmine. • HBB reduces spasms of neural and potentially non-neural origin. [ABSTRACT FROM AUTHOR]

Polystichum lonchitis L. is a fern belonging to the family Dryopteridaceae. The present study was conducted to evaluate its pharmacological, antioxidant, and phytochemical properties, and to conduct GC–MS screening of P. lonchitis. The acetic acid-induced writhing test, yeast-induced hyperpyrexia method, carrageenan-induced rat paw edema model, and charcoal meal test model were carried out to assess analgesic, antipyretic, anti-inflammatory, and antispasmodic activity, respectively. DPPH was used as an antioxidant, while the phytochemical screening was conducted using standard scientific methods. Among the pharmacological activities, the most significant effects were observed in the analgesic and anti-inflammatory activities, followed by the antipyretic and antispasmodic activities, at a dose of 450 mg/kg after the 4th hour, compared with 150 mg/kg and 300 mg/kg. For the evaluation of antioxidant activities, the most significant results were detected in the methanolic and aqueous extracts. The detection of flavonoids and phenol occurred most significantly in the methanolic extract, and then in the ethanolic and aqueous extracts. The main compounds detected using GC–MS analysis with a high metabolic rate was 𝛼-D-Galactopyranoside, which had a metabolic rate of 0.851, and methyl and n-hexadecanoic, which had a metabolic rate of 0.972. Overall, the results suggested that P. lonchitis had a strong potential for pharmacological activities. The suggested assessment provided a way to isolate the bioactive constituents and will help to provide new medicines with fewer side effects. Due to the fern’s effectiveness against various diseases, the results provide clear evidence that they also have the potential to cure various diseases.

This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. The phytochemicals were detected using gas chromatography–mass spectrometry (GC–MS) while the in vivo antidiarrheal test was done using Swiss albino mice. To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. GC–MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders. [ABSTRACT FROM AUTHOR]

Background: Caralluma dalzielii N.E. Brown is commonly referred to as "Karan massalanci" in the Northwest Nigeria where it is used in treating several ailments including pain, diarrhea and stomach issues. Objectives: This study was aimed to investigate the antidiarrheal and antioxidant activities of aqueous aerial parts extract of Caralluma dalzielii. Materials and Methods: The aqueous aerial parts extract of Caralluma dalzielii (CDE) (100, 200 and 400 mg/kg) was evaluated for antidiarrheal properties against gastrointestinal motility, castor oil-induced and prostaglandin-E2 (PGE2) enteropooling models in Wistar rats. Its antioxidant properties were studied by determining the total phenolic content (TPC) using Folin-Ciocalteu reagent, its free radical scavenging activity using 1, 1-Diphenyl-2-Picrylhydrazyl (DPPH) and its ferric reducing antioxidant power (FRAP) assays using potassium ferrocyanide ferric chloride methods. Ascorbic acid was used as the reference. Spasmolytic effect was studied in isolated rabbit jejunum preparations in an organ bath experiment using acetylcholine (ACh). Results: CDE significantly (p<0.05) reduced gastrointestinal transit of charcoal meal and the total number of diarrheal feces in the animals. The total phenolic content was determined to be 36.67±3.33 mg GAE/g. IC50 value of 63.44 mg/mL was calculated in DPPH assay. The FRAP value was found to increase as the concentration of the extract increased. CDE inhibited acetylcholine-induced contraction of the rabbit jejunum in a concentration dependent manner with complete inhibition at 20.48 mg/mL of the extract. Conclusion: The extract of Caralluma dalzielii possesses antidiarrheal activities which may be related to its antimotility, antioxidant and antispasmodic properties. [ABSTRACT FROM AUTHOR]

The review article presents current data on functional disorders of the biliary system, taking into account the latest recommendations of experts of the Rome Foundation (Rome Criteria IV, 2016) and the Russian Gastroenterological Association (specialized clinical recommendations, 2018). According to modern concepts, biliary dysfunction is a group of functional disorders of the biliary system caused by motor disorders and increased visceral sensitivity. According to the literature data, the prevalence of functional disorders of GB and OS is 10-15%, and violation of OS function is revealed in 30-40% of patients who underwent cholecystectomy (CE). The presence of biliary pain is an obligatory condition in the diagnosis of functional disorders of GB and OS. Bilirubin and serum transaminases (AST, ALT) levels may increase in biochemical blood analysis in patients with functional OS disorder of biliary type, and pancreatic amylase and lipase in case of functional OS disorder of pancreatic type. Ultrasound examination of abdominal organs is considered to be the priority among instrumental methods. This technique allows to exclude organic lesions of both the GB and visualized ducts, and adjacent organs (GSD, biliary tract, liver and pancreas neoplasms). Magnetic resonance cholangiopancreatography (MRCP) is used as a clarifying method, which allows to visualize the state of biliary ducts throughout. Ultrasonic cholecystography is used to assess the contractile activity of the GB. When duct dilation is detected and/or when liver/pancreatic enzyme levels are elevated in the absence of changes according to MRCP data, it is reasonable to perform an endoscopic ultrasound examination. According to the latest recommendations of the Russian Gastroenterological Association (2018), the foundation of pharmacotherapy for this group of diseases are antispasmodics and ursodeoxycholic acid (UDCA).

Background: Fuchsia magellanica Lam. (Onagraceae) is a native plant of the Andean-Patagonian region, and it is also naturalized in Argentina and other parts of the world. Leaves are used for treating indigestion, stomachache, as sedative, for difficult delivery and as antiemmenagogue. However, up to now the pharmacological basis of such uses were not studied. Purpose: This work evaluates the gastrointestinal, uterine and sedative effects of leaves (L) and flowers (F) tinctures of F. magellanica from wild patagonian (T-Fm-P) and naturalized (T-Fm-BA) plants, as well as the mechanism of action and the flavonoids profile of both plants. Methods: Phytochemical studies were evaluated by using TLC and HPLC methodologies. The ex-vivo effects of T-Fm-BA and T-Fm-P were evaluated on contractile concentration-response curves (CRC) of carbachol (CCh) and calcium (Ca2+) in rat isolated intestinal and uterine tissues. In vivo tests for intestinal transit, elevated cross plus-maze and open-field tests were performed in mice. Results: Wild and cultivated leaves and flowers ethanolic extracts induced antispasmodic effect, as a non-competitive inhibitor of the CCh-CRC in intestine, with IC50 of 272.8 ± 64.3 µg/ml for T-L-Fm-P and 257.4 ± 36 µg/ml for T-L-Fm-BA. A similar effect was obtained in Ca2+-CRC with IC50 of 152.9 ± 29.1 µg/ml and 138.4 ± 48.6 µg/ml respectively. Mice intestinal transit was reduced at oral doses of 73.5 mg/kg of T-L-Fm-P. In uterine tissues, both T-L-Fm reduced the contractions of CCh CRC´s as non-competitive antagonists, with IC50 near those in intestine. The T-L-Fm-BA also inhibited the serotonin CRC´s and contribution of other relaxing mechanisms was investigated. Although extracts didn't show anxiolytic effect in the elevated cross plus-maze test, they reduced the spontaneous activity of mice in the open-field at 32.7 mg/kg T-L-Fm-P and 41.7 mg/kg T-L-Fm-BA. Conclusions: Leaves and flowers ethanolic extracts from wild and cultivated plant F. magellanica showed intestinal and uterine antispasmodic effects, mainly by interfering with Ca2+ influx. In mice, the ethanolic extracts reduced the intestinal transit and showed sedative effect. The effects agree with the presence of flavonoids, such as quercetin and kaempferol. This is the first study which gives experimental support for some of the traditional uses of F. magellanica.

Extracts from Drosera rotundifolia are traditionally used to treat cough symptoms during a common cold. The present study aimed to investigate the impact of extracts from D. rotundifolia and active compounds on the respiratory tract. Tracheal slices of C57BL/6N mice were used ex vivo to examine effects on airway smooth muscle (ASM) and ciliary beat frequency (CBF). Phosphodiesterase (PDE) inhibition assays were carried out to test whether PDE1 or PDE4 are targeted by the active compounds. An ethanol–water extract, as well as an aqueous fraction of this extract, exerted antispasmodic properties against acetylcholine-induced contractions. In addition, contractions induced by 60 mM K+ were abrogated by the aqueous fraction. Effects on ASM could be attributed to the flavonoids quercetin, 2″-O-galloylhyperoside and hyperoside. Moreover, the Drosera extract and the aqueous fraction increased the CBF of murine tracheal slices. Quercetin and 2″-O-galloylhyperoside were identified as active compounds involved in the elevation of CBF. Both compounds inhibited PDE1A and PDE4D. The elevation of CBF was mimicked by the subtype-selective PDE inhibitor rolipram (PDE4) and by 8-methoxymethyl-IBMX. In summary, our study shows, for the first time, that a Drosera extract and its flavonoid compounds increase the CBF of murine airways while antispasmodic effects were transferred to ASM.

Objective: To assess the effectiveness of hyoscine‐N‐butylbromide on the duration of the first stage of labor among nulliparous women. Methods: A randomized double‐blind placebo‐controlled study among 126 nulliparous women admitted in the active phase of labor to a teaching hospital in Sagamu, Nigeria, from January to August 2018. Based on the inclusion criteria, women were recruited and randomized to the study or control group, and given intravenous hyoscine‐N‐butylbromide 20 mg (1 mL) or sterile water (1 mL), respectively, during the active phase. Labor progress and outcomes were compared between the groups. Results: The mean ± SD duration of active phase of first stage of labor was significantly shorter in the hyoscine‐N‐butylbromide group (324.9 ± 134.6 min) than in the control group (392.7 ± 119.6 min) (P = 0.004). The rate of cervical dilatation was 1.4 ± 0.8 cm/h in the hyoscine‐N‐butylbromide group and 1.0 ± 0.5 cm/h in the control group (P = 0.004). There were no significant differences in fetal heart rate, maternal vital signs, or Apgar scores between the two groups. Conclusion: Hyoscine‐N‐butylbromide was found to be effective in shortening the duration of the first stage of labor without adverse outcomes for mother or neonate. The trial was registered with the Pan African Clinical trials Registry (PACTR), protocol number: PACTR201808146688942 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3532). Synopsis: Hyoscine‐N‐butylbromide was found to be effective in reducing the duration of the first stage of labor and had no adverse effects among nulliparous women. [ABSTRACT FROM AUTHOR]

Background: Probiotics and antispasmodics have been tested extensively in the management of symptoms of irritable bowel syndrome (IBS), but they have rarely been evaluated in combination. The objective of this pilot study was to assess the efficacy of treatment with the probiotic formulation i3.1 (Lactobacillus plantarum CECT7484 and CECT7485 and Pediococcus acidilactici CECT7483), with or without the addition of the antispasmodic alverine/simethicone, in improving IBS-related quality of life (QoL) and reducing abdominal pain and diarrhea in patients with IBS. Methods: This was a randomized, placebo-controlled clinical trial with 3 parallel arms (probiotic, probiotic plus antispasmodic, and placebo). Patients with IBS (N = 55) were recruited at the Gastroenterology Department of the Juárez Hospital (México City). QoL was assessed with the IBS-QoL questionnaire, abdominal pain with a visual analog scale, and stool consistency with the Bristol scale. Results: The IBS-QoL rate of response (ITT analysis) was 50.0% for patients in the group with probiotic alone, 68.4% in the group with probiotic plus antispasmodic, and 16.7% in the group with placebo after 6 weeks of treatment (p = 0.005). Response to abdominal pain was reported by 38.9% of patients treated with probiotic, 57.9% with probiotic plus antispasmodic, and 16.7% with placebo (p = 0.035). Regarding stool consistency, a response to treatment was reported by 44.4% of patients treated with probiotic, 57.9% with probiotic plus antispasmodic, and 16.7% with placebo (p = 0.032). Conclusion: The results are consistent with previous studies on the use of the i3.1 probiotic formulation for the management of symptoms in IBS patients, and the addition of an antispasmodic improves its observed effects. [ABSTRACT FROM AUTHOR]

According to the Recommendations of the Scientific society of gastroenterologists of Russia for the diagnosis and treatment of cholelithiasis (GI), GI is a multifactorial disease of the hepatobiliary system and one of the most common diseases of the digestive system. It is known that in the vast majority of cases, GI develops as a result of the complex influence of many risk factors. Thus, the change in the qualitative and quantitative composition of bile, as well as a history of gastrectomy, papillosphincterotomy, the right-hand hemicolectomy, cholesterosis gall bladder, chronic hepatitis, peptic ulcer of the duodenum, duodenostasis contributes to the reduction of the contractile function of the gallbladder and the development of hypertonicity of the sphincter of Oddi. Current understanding of mechanisms of formation of gallstones is based on many studies, which proved that the GSD is a result of destabilized bile-damaged hepatocytes, the subsequent nucleation of crystals of monohydrate of cholesterol crystallization in the mucin matrix on the background of hypomotor dysfunction of the gall bladder. After anamnesis and General clinical examination, the main diagnostic method for suspected gastrointestinal tract is ultrasound (ultrasound). However, differentiation of stone types by ultrasound is generally not possible. The most modern diagnostic method is CT with an assessment of the density of stones on the Hounsfield scale. Today, it is common to distinguish three main types of gallstones found in humans: cholesterol, black and brown pigment stones. Methods of treatment of gastrointestinal tract can be divided into invasive or surgical, minimally invasive and non-invasive. Recommending a patient with gastrointestinal surgery, you should always remember that surgical treatment is the elimination of the consequences of cholelithiasis, and not the treatment of its essence. So, after the successful application of udhc in the early 80-ies of the last century for the dissolution of gallstones, drug litholysis, opened a new era in the treatment of gastrointestinal tract and reduced the amount of indications for surgical treatment.

Apart from the nutritional value, Cucumis sativus L. has also been used in the traditional medicine of Iran, Pakistan, and India. Its seeds are used by herbalists to treat gastrointestinal, respiratory, and urinary problems. However, more investigations are required to explain its mechanisms for treating GI, respiratory, and urinary diseases. Accordingly, the aim of the present work was to investigate the antispasmodic, bronchodilator, and antidiarrheal activities of C. sativus seeds extracts and the underlying mechanisms of action. For this purpose, sequential extracts of C. sativus seeds were prepared in n-hexane, dichloromethane, ethanol, and water. Bioactive compounds in C. sativus seed extracts were identified and quantified by utilizing LC ESI–MS/MS and HPLC. Moreover, network pharmacology and molecular docking were employed to examine the antispasmodic and bronchodilator effects of the bioactive substances in the extracts. In vitro and in vivo experiments were also conducted to validate the mechanistic insights gained from the in silico analysis. Results indicated the presence of kaempferol with a concentration of 813.74 µg/g (highest concentration) in the seed extract of C. sativus, followed by quercetin (713.83 µg/g), narcissin (681.87 µg/g), and orientin (676.19 µg/g). In silico investigations demonstrated that the bioactive chemicals in C. sativus seeds inhibited the expression of the target genes involved in smooth muscle contraction and calcium-mediated signaling. Sequential seed extracts of C. sativus caused a dose-dependent relaxant response for spasmolytic reaction and resulted in a relaxation of K+ (80 mM) spastic contraction. In animal models, C. sativus seed extracts exhibited partial or complete antiperistalsis, antidiarrheal, and antisecretory actions. By modulating the contractile response through calcium-mediated signaling target proteins, C. sativus seeds generated bronchodilator, antispasmodic, and antidiarrheal therapeutic effects.

Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have significant antileishmanial activity with LC50 of Log10 (1.83±0.0026) x10-6mg/ml, potent relaxant activity on rabbits' jejunal preparations with respective EC50 = 1.46±0.15mg/ml for spontaneous activity. For KCl (80mM) induced contractions, EC50=0.26±0.02mg/ml. In CCRCs, the oil produced a right shift as exhibited by verapamil. More, its relaxant activity, which is mediated through calcium channel blocking mechanism, proves a rationale for its traditional use in gut spasm. [ABSTRACT FROM AUTHOR]

The present study attempted to evaluate and rationalize the medicinal use of the methanolic extract of the fruits of Balanites aegyptiaca (B. aegyptiaca) in the treatment of hyperactive gut disorders. The in vivo, castor oil-induced diarrhea model in mice was followed to test its antidiarrheal effect. To test the antispasmodic effect and to explore its pharmacodynamic details, isolated small intestines (ileum) obtained from rats were selected to provide physiological conditions for the ex vivo assays. In the in vivo assays, the orally administered extract of B. aegyptiaca protected mice from diarrheal drops with resultant percent inhibitions of 40% and 80% at the respective doses of 200 mg/kg and 400 mg/kg, while the highest protection (100%) was observed with a positive control drug, loperamide, at 10 mg/kg. In the ileum, B. aegyptiaca produced an antispasmodic effect in a concentration-dependent manner by inhibiting the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms with resultant EC50 values of 1.44 mg/mL (1.08–1.78) and 1.27 mg/mL (0.98–1.66), respectively. Papaverine, a known phosphodiesterase enzyme (PDE) inhibitor and blocker of Ca++ channels (CCB), also inhibited both CCh and high K+ induced contractions at comparable EC50 values of 8.72 µM (7.92–9.24) and 8.14 µM (7.62–8.84), respectively. Contrary to the extract and papaverine, verapamil showed distinctly higher potency in regard to inhibiting high K+, compared to CCh-evoked spasms that had EC50 values of 0.16 µM (0.13–0.261) and 2.54 µM (2.28–2.92), respectively. The inhibitory effects of B. aegyptiaca on PDE were further confirmed when the pre-incubated extract shifted the isoprenaline-mediated relaxation curves (CRCs) towards the left, similar to papaverine, whereas the CCB-like effect was confirmed when the pre-incubated tissues with B. aegyptiaca caused deflection in the Ca++ CRCs towards the right, constructed in Ca++ free medium with suppression of the maximum response. Thus, this study provides detailed, mechanistic support for the medicinal use of B. aegyptiaca in the treatment of hyperactive gut disorders.

This present study evaluated and rationalized the medicinal use of the fruit part of Acacia nilotica methanolic extract. The phytochemicals were detected using gas chromatography–mass spectrometry (GC–MS) while the in vivo antidiarrheal test was done using Swiss albino mice. To determine the details of the mechanism(s) involved in the antispasmodic effect, isolated rat ileum was chosen using different ex vivo assays by maintaining a physiological environment. GC–MS results showed that A. nilotica contained pyrogallol as the major polyphenol present (64.04%) in addition to polysaccharides, polyphenol, amino acid, steroids, fatty acid esters, and triterpenoids. In the antidiarrheal experiment, A. nilotica inhibited diarrheal episodes in mice significantly (p < 0.05) by 40% protection of mice at 200 mg/kg, while 80% protection was observed at 400 mg/kg by the orally administered extract. The highest antidiarrheal effect was observed with loperamide (p < 0.01), used as a control drug. In the ex vivo experiments, A. nilotica inhibited completely in increasing concentrations (0.3 to 10 mg/mL) the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms in ileum tissues at equal potencies (p > 0.05), similar to papaverine, a dual inhibitor of the phosphodiesterase enzyme (PDE) and Ca++ channels. The dual inhibitory-like effects of A. nilotica on PDE and Ca++ were further validated when A. nilotica extract (1 and 3 mg/mL)-pre-incubated ileum tissues potentiated and shifted isoprenaline relaxation curves towards lower doses (leftward), similar to papaverine, thus confirming the PDE inhibitory-like mechanism whereas its CCB-like effect of the extract was confirmed at 3 and 5 mg/mL by non-specific inhibition of CaCl2-mediated concentration response curves towards the right with suppression of the maximum peaks, similar to verapamil, used as standard CCB. Thus, this study characterized the chemical composition and provides mechanistic support for medicinal use of A. nilotica in diarrheal and hyperactive gut motility disorders.

Objective: Papaverine is a topical vasodilator commonly used during microvascular surgery to inhibit undesired vasoconstriction. A previous national shortage of papaverine prompted evaluation of an alternative, effective vasodilator. This study aims to assess the experience of a solution of verapamil and nitroglycerin (VG) as a potential alternative pharmacologic vasodilator. Study Design: Retrospective case series. Setting: Two tertiary academic medical centers. Subjects and Methods: Among 298 patients, 306 consecutive free tissue transfers performed between 2014 and 2017 for head and neck defect reconstruction utilized a VG solution. Patient and flap characteristics, intraoperative patient and flap complications, and postoperative complications were reviewed. Diameter of the cervical recipient artery was measured intraoperatively before and after topical application of the VG solution in a subset of 43 patients (44 flaps). Results: Flaps included fibula, radial forearm, subscapular system, and anterolateral thigh. In total, 3 (0.98%) flaps failed with varied etiology unrelated to the VG solution (venous thrombosis, arterial anastomosis thrombosis, physical damage to the perforator). Specific to topical application of the VG solution, the mean recipient artery diameter increased from 2.1 to 3.1 mm, a 48% increase (P <.01). There were no intraoperative cardiac events or complications attributable to the VG solution. Conclusion: We describe the use of a VG solution for pharmacologic vasodilation during microvascular free tissue transfer. Its use was associated with an acceptable incidence of adverse events, none of which were directly attributable to the VG solution. Apparent and sustained vasodilation was demonstrated. The VG solution represents a safe and efficacious alternative to papaverine in microvascular surgery. [ABSTRACT FROM AUTHOR]

Background: The leaves of Origanum majorana ( O. majorana ) are traditionally renowned for treating diarrhea and gut spasms. This study was therefore planned to evaluate its methanolic extract., Methods: Gas chromatography-mass spectrometry (GC-MS) was used to identify the phytochemicals, and Swiss albino mice were used for an in vivo antidiarrheal assay. Isolated rat ileum was used as an ex vivo assay model to study the possible antispasmodic effect and its mechanism(s)., Results: The GC-MS analysis of O. majorana detected the presence of 21 compounds, of which alpha-terpineol was a major constituent. In the antidiarrheal experiment, O. majorana showed a substantial inhibitory effect on diarrheal episodes in mice at an oral dosage of 200 mg/kg, resulting in 40% protection. Furthermore, an oral dosage of 400 mg/kg provided even greater protection, with 80% effectiveness. Similarly, loperamide showed 100% protection at oral doses of 10 mg/kg. O. majorana caused complete inhibition of carbachol (CCh, 1 µM) and high K+ (80 mM)-evoked spasms in isolated ileal tissues by expressing significantly higher potency ( p < 0.05) against high K+ compared to CCh, similar to verapamil, a Ca++ antagonist. The verapamil-like predominant Ca++ ion inhibitory action of O. majorana was further confirmed in the ileal tissues that were made Ca++-free by incubating the tissues in a physiological salt solution having ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The preincubation of O. majorana at increasing concentrations (0.3 and 1 mg/mL) shifted towards the right of the CaCl2-mediated concentration-response curves (CRCs) with suppression of the maximum contraction. Similarly, verapamil also caused non-specific suppression of Ca++ CRCs towards the right, as expected., Conclusions: Thus, this study conducted an analysis to determine the chemical constituents of the leaf extract of O. majorana and provided a detailed mechanistic basis for the medicinal use of O. majorana in hyperactive gut motility disorders., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Introduction: Zataria multiflora Boiss. is an indigenous herbal plant found in many parts of Iran. This herb is traditionally used as a remedy for treating gastrointestinal disorders including diarrhea. Despite the existence of few pharmacological evidences which support the antispasmodic action of Z. multiflora in vitro, there is no scientific report about therapeutic efficacy of Z. multiflora in animal models. The objective of this research was to investigate the antispasmodic activity of hydroalcoholic and hexane extracts of Z. multiflora on intestinal peristaltic movement as well as assessment of its antidiarrheal action in mice. Methods: Dried leafy branches of Z. multiflora were coarsely powdered and subjected to extraction by ethanol or hexane in a percolator apparatus. Antispasmodic activity of Z. multiflora in vivo was assessed by investigating effect of the extracts on intestinal charcoal meal transit. The antidiarrheal activity of Z. multiflora extracts was evaluated by castor oil and magnesium sulfate‑induced diarrhea. The inhibitory effects of the extracts were compared with the standard drug loperamide. Results: The antispasmodic activity of Z. multiflora (20 & 40 mg/kg) hydroalcoholic and hexane extracts was confirmed by a reduction in the distance traveled by charcoal meal alongside the small intestine. Z. multiflora extracts (20 & 40 mg/kg) also significantly attenuated the castor oil and magnesium sulfate‑induced diarrhea. Loperamide was more efficacious in reducing number of total stools in both models of diarrhea. Conclusion: The obtained results have established a pharmacological evidence for the folkloric use of the Z. multiflora as an antidiarrhoeal and spasmodic agent.