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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]

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.

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.

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.

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]

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.)

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., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Functional bowel disorders (FBD) have a major potential to degrade the standards of public life. Juniperus oxycedrus L. (J. oxycedrus) (Cupressaceae) has been described as a plant used in traditional medicine as an antidiarrheal medication. The present study is the first to obtain information on the antispasmodic and antidiarrheic effects of J. oxycedrus aqueous extract through in vitro and in vivo studies. An aqueous extract of J. oxycedrus (AEJO) was extracted by decoctioning air-dried aerial sections of the plant. Antispasmodic activity was tested in an isolated jejunum segment of rats exposed to cumulative doses of drogue extract. The antidiarrheic activity was tested using diarrhea caused by castor oil, a transit study of the small intestine, and castor oil-induced enteropooling assays in mice. In the jejunum of rats, the AEJO (0.1, 0.3 and 1 mg/ml) diminished the maximum tone induced by low K + (25 mM), while it exhibited a weak inhibitory effect on high K + (75 mM) with an IC 50 =0.49 ± 0.01 mg/ml and IC 50 =2.65 ± 0.16 mg/ml, respectively. In the contractions induced by CCh (10 -6 M), AEJO diminished the maximum tone, similar to that induced by low K + (25 mM). with an IC 50 =0.45 ± 0.02 mg/ml. The inhibitory effect of AEJO on low K + induced contractions was significantly diminished in the presence of glibenclamide (GB) (0.3 µM) and 4-aminopyrimidine (4-AP) (100 µM), with IC 50 values of 1.84 ± 0.09 mg/ml. and 1.63 ± 0.16 mg/ml, respectively). The demonstrated inhibitory effect was similar to that produced by a non-competitive antagonist acting on cholinergic receptors and calcium channels. In castor oil-induced diarrhea in mice, AEJO (100, 200, and 400 mg/kg) caused an extension of the latency time, a reduced defecation frequency, and a decrease in the amount of wet feces compared to the untreated group (distilled water). Moreover, it showed a significant anti-motility effect and reduced the amount of fluid accumulated in the intestinal lumen at all tested doses. These findings support the conventional use of Juniperus oxycedrus L. as a remedy for gastrointestinal diseases.