Antisecretory Effect Research Articles

Mapping the effect of the antisecretory factor on GABAA receptor α1 and α6 subunits in cerebellar granule cells in vitro

The Antisecretory Factor (AF) is a protein that can reduce intestinal hypersecretion and various inflammation disorders in vivo. Discovered in many mammalian tissues and plasma, its mechanism of action remains unknown. Interestingly, its induction has been found to counteract vertigo in patients with Méniere's disease. This suggests an inherent ability to control body balance and posture, an activity that may play a role in cerebellar function. Therefore, it may be worthwhile to investigate whether this activity can inhibit neuronal cells involved in cerebellar circuitries and its potential action on enteric nervous system ganglia, which could explain its antisecretory effect in the intestine.Previously, we studied the role of AF on GABAA receptors in cerebellar granule cells, taking advantage of electrophysiology and evaluating the effects of the administration of AF-16, an AF peptide. Treatment with AF-16 increased GABAA receptor responses, especially those containing the α6 subunit. Here, we performed immunofluorescence experiments by staining α1 and α6 subunits before and after incubation with AF-16, analyzed super-resolved images comparing pre- and post-treatment maps and critically examined these experimental results with our previous electrophysiological data to shed light on the mechanisms of action of AF protein on GABAA receptor subpopulations, specifically the "fast" receptors of αn β2/3 γ2 composition that contain either the α1 or the α6 subunit.The results indicate that the α6 subunit is redistributed, with a decrease in neurites and an increase in soma. Conversely, the α1 subunit shows opposite results, with an increase in neurites and a decrease in soma.

Protective effect of Phlogacanthus thyrsiflorus Nees against experimentally induced gastric mucosal lesions in rats: Experimental evidence from biochemical and histological analysis

Phlogacanthus thyrsiflorus Nees (Acanthaceae) is traditionally used in the North East Himalayan region to treat stomach issues, including gastritis. This study aimed to investigate the gastroprotective effect of 70% aqueous ethanol extract of Phlogacanthus thyrsiflorus flowers (PTE), standardized by HPTLC and LC-MS/MS, and to establish its possible mechanisms. The gastroprotective effect of PTE, at doses of 200 and 400 mg/kg body weight, was evaluated using both physical (pylorus ligation, PL; cold restraint stress, CRS) and chemical (ethanol, EtOH) ulcerogens-induced gastric ulcers in Wistar rats. Animals were randomly divided into control, ulcer control, positive control and PTE-treated groups, with PTE administered orally twice daily for 5 days. The protective effect of PTE was assessed through various gastric ulcer parameters, including gastric pH, gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant markers, and gastric histopathology. HPTLC and LC-MS/MS confirmed the presence of gallic acid, naringenin, β-sitosterol and ascorbic acid in PTE. The active components of PTE showed significant dose-dependent inhibition of ulcer index, with reductions of 28.59-50.03% in PL, 27.69-53.23% in EtOH and 31.14-57.53% in CRS models (P< 0.01). Additionally, PTE at 400 mg/kg significantly increased gastric pH by 23.41%, mucus content by 33.69%, and NP-SH levels by 37.24%. PTE also demonstrated significant antioxidant potential and histopathological studies confirmed its protective effect. The study suggests that the anti-ulcer effect of PTE may be attributed to its ability to preserve adhered gastric mucus, exhibit antisecretory effects, and scavenge free radicals.

The effect of rabeprazole on the secretory and motor function of the gastrointestinal tract

Parietal cell proton pump inhibitors (PPIs) have become firmly established in clinician practice. When discussing the features of their action, as a rule, researchers focus on their antisecretory effect. In the available literature, we found only a single report on the effect of PPIs on the motor-evacuation function of the gastrointestinal tract (GIT). We have found that the PPI rabeprazole not only has an antisecretory effect, but also normalizes the motor-evacuation function of all parts of the gastrointestinal tract. In this regard, it can be used in patients with gastric hypersecretion in functional gastrointestinal disorders (FGID) with impaired motor-evacuation function. Aim. To study the effect of the antisecretory drug rabeprazole on the state of gastrointestinal motility in patients suffering from FGID of the gastrointestinal tract and overlap syndrome (overlap syndrome) with functional dyspepsia (FD) with gastric hypersecretion and irritable bowel syndrome (IBS). Material and methods. We examined 30 patients suffering from FGID of the gastrointestinal tract and cross syndrome - FD with gastric hypersecretion and IBS. To relieve clinical symptoms of FD, the drug rabeprazole 20 mg was prescribed once a day for 14 days. Before and after the start of treatment, patients were examined with VAS and SF-36 tests, intragastric pH-metry and peripheral electrogastroenterocolography (EGECG) were performed. Results. In all 30 patients with FGID of the gastrointestinal tract with FD and overlap syndrome with IBS, gastric hypersecretion was eliminated within 3 hours after taking 20 mg of rabeprazole. 2 weeks after the start of treatment, abdominal pain and heartburn were completely eliminated in 28 (93.3%) patients. In all (100%) patients with FGID of the gastrointestinal tract with gastric hypersecretion and overlap syndrome, after two weeks of treatment, sour belching disappeared, and nausea disappeared in 23 (77%) patients. Rabeprazole therapy in the examined individuals was accompanied by a marked improvement in the quality of life in all assessed SF-36 parameters. 2 weeks after starting rabeprazole, in patients with FGID of the gastrointestinal tract and overlap syndrome of FD and IBS, the frequency of bowel movements and stool quality were normalized, and according to the results of EGECG, the relative myoelectric activity (P(i)/PS) of the gastrointestinal tract and the rhythmicity coefficient (Kritm) were normalized. Conclusion. Rabeprazole quickly neutralizes gastric secretion and helps eliminate symptoms of FD. It also has a beneficial effect on the motor-evacuation function of all parts of the gastrointestinal tract, normalizing the frequency of bowel movements, stool quality and myoelectric activity of all parts of the gastrointestinal tract according to EGECG. Rabeprazole can be used in patients with FGID with FD with gastric hypersecretion and overlap syndrome with IBS.

Potential of Anti-Secretory and Cytoprotective Effect from Azadiradione as GERD Prevention

Gastroesophageal Reflux Disease (GERD) is a pathological state due to stomach reflux within the esophagus, which causes necrosis of esophageal mucosa, resulting in erosions, ulcers, and other complications. GERD is still a growing global issue with 783.95 million cases worldwide in 2019. Although PPIs were used as medications to treat GERD, there were refractions and adverse effects to the patients. Azadiradione, terpenoids that can be found in A. indica and various plants, has potential as alternative H+/K+ ATPase inhibitor sources with its anti-secretory and cytoprotective activity. Some studies explain that there is also adverse effects of azadiradione. Further research are needed to determine alternative sources, safety dosage, usage duration, side effects, also drug-food or drug-drug interaction of azadiradione.

Somatostatin receptor 1 (SSTR1) expression as a potential predictive biomarker for response to androgen receptor signaling inhibitor (ARSI) therapy in metastatic castration-resistant prostate cancer (mCRPC).

180 Background: Overcoming ARSI resistance is an unmet need for mCRPC patients. Known resistance mechanisms include genetic alterations augmenting androgen receptor (AR) function (e.g., amplifications of the AR gene and its enhancer and AR mutations) and treatment-emergent evolution from an AR-driven to an AR-indifferent phenotype such as small cell neuroendocrine prostate cancer. Other mechanisms remain unexplored. Methods: To phenotype ARSI-resistant prostate cancer, we compared the RNA-seq profiles of paired metastatic biopsies from 31 mCRPC patients obtained before the initiation of first-line abiraterone or enzalutamide, and upon radiographic progression. The patient samples were obtained from two independent cohorts, the Stand Up To Cancer/Prostate Cancer Foundation (SU2C/PCF) West Coast Prostate Cancer Dream Team (WCDT) and a multi-institutional cohort from the Netherlands sequenced through the Hartwig Medical Foundation. We first evaluated RNA-seq data to identify the most differentially expressed genes and then performed survival analysis in the retrospective WCDT cohort (n=115, including 54 ARSI-naïve and 61 ARSI-experienced tumors) to assess the association between gene expression and overall survival, defined as the time interval from biopsy to death from any cause. Results: In the analysis of paired RNA-seq data from 31 mCRPC patients, SSTR1 was identified as the most significantly altered gene; SSTR1 expression was consistently decreased in post-treatment, ARSI-resistant tumors (log2[fold change]=-2.5, p=1.08×10-16). SSTR1 encodes somatostatin receptor 1, a G-protein coupled receptor that, when activated by the endogenous peptide hormone somatostatin or exogenous somatostatin analogues, mediates anti-proliferative, anti-migratory, and anti-secretory effects on target cells. Retrospective analysis in the 115 WCDT patients demonstrated that low SSTR1 expression was associated with worse overall survival ( p=0.047); ARSI treatment improved survival for patients with SSTR1-high (≥ median) tumors (HR=0.29, p=0.0002) more significantly than those with SSTR1-low (&lt; median) tumors (HR=0.67, p=0.17), with an interaction ( SSTR1 expression * ARSI treatment) towards statistical significance ( p=0.0598). A differential survival benefit of ARSI therapy with respect to SSTR1 expression was observed only among the 61 ARSI-experienced patients. Conclusions: SSTR1 expression is a potential predictive biomarker for response to ARSI in mCRPC, with higher SSTR1 expression predicting better response. This observation could be explained by an anti-tumor effect of SSTR1 signaling. Further work is warranted to prospectively validate these findings and to investigate SSTR1 as an actionable drug target to overcome ARSI resistance.

Anti H. pylori, anti-secretory and gastroprotective effects of Thymus vulgaris on ethanol-induced gastric ulcer in Sprague Dawley rats.

The objectives of the present study were to evaluate the acute toxicity, gastroprotective, therapeutic, anti-inflammatory and anti H. pylori activities of T. vulgaris total plant extract against ethanol-induced gastric ulcers in Sprague Dawley rats. Animals were divided into five groups i.e G-1 (Normal Control), Group 2 (ulcer control) were administered orally with 0.5% Carboxymethylcellulose (CMC), Group 3 (omeprazole treated) was administered orally with 20 mg/kg of omeprazole and Groups 4 and 5 (Low dose and High dose of the extract) were administered orally with 250, and 500 mg/ kg of Thymus vulgaris extract, respectively. After 1 hour, the normal group was orally administered with 0.5% CMC (5 ml/kg), whereas absolute alcohol (5ml/ kg) was orally administered to the ulcer control group, omeprazole group, and experimental groups. Stomachs were examined macroscopically and microscopically. Grossly, rats pre-treated with T. vulgaris demonstrated significantly decreased ulcer area and an increase in mucus secretion and pH of gastric content compared with the ulcer control group. Microscopy of gastric mucosa in the ulcer control group showed severe damage to gastric mucosa with edema and leukocytes infiltration of the submucosal layer. However, rats pretreated with omeprazole or Thyme vulgaris exhibited a mild to moderate disruption of the surface epithelium and lower level of edema and leukocyte infiltration of the submucosal layer. The T. vulgaris extract caused up-regulation of Hsp70 protein, down-regulation of Bax protein, and intense periodic acid Schiff uptake of the glandular portion of the stomach. Gastric mucosal homogenate of rats pre-treated with T. vulgaris exhibited significantly increased superoxide dismutase (SOD) and catalase (CAT) activities while malondialdehyde (MDA) level was significantly decreased. Based on the results showed in this study, Thymus vulgaris extract can be proposed as the safe medicinal plants for use and it has considerable gastroprotective potential via stomach epithelium protection against gastric ulcers and stomach lesions.

Toxicological impact of rabeprazole and evaluation of toxic effects on the plant-based eukaryotic test models

Background: Rabeprazole (RPZ), a widely used proton pump inhibitor, is known to have toxic effects on human beings. Objective: To evaluate the current understanding of its toxicological effects on humans and animals, a literature and laboratory-based study was conducted. Methods: A comprehensive search of published literature was conducted in various databases up until April 2020, using specific keywords. Additionally, toxic effects of RPZ-Na (0.025-0.4 mM) were evaluated on Allium cepa, Allium sativum and Cicer arietinum at different exposure times using CuSO4 as a reference standard. Results: The literature review revealed that RPZ has a wide range of side effects including nausea, vomiting, diarrhea, headache, rhinitis, myalgia, pharyngitis, abdominal pain, dyspepsia, and eye disorders. Chronic exposure to RPZ has also been associated with significant biochemical and hematological alterations, as well as various toxicological effects such as hypergastrinemia, hyperplasia, atrophy of gastric glands, gastric anti-secretory effect, and hypochlorhydria. The laboratory analysis showed that RPZ-Na concentration-dependently inhibited root length of A. cepa and A. sativum, as well as shoot and root lengths of C. arietinum. Conclusions: This study highlights the toxicological impacts of RPZ and its formulations on human and animals. Results suggest that RPZ-Na has a concentration-dependent toxic effect on A. cepa, A. sativum, and C. arietinum. Therefore, it is important to take adequate precautions during its long-term use.

From biology to clinical practice: antiproliferative effects of somatostatin analogs in neuroendocrine neoplasms.

Somatostatin analogs (SSA), specifically octreotide and lanreotide, have demonstrated antiproliferative effects in patients with neuroendocrine tumors (NET), a group of rare malignancies of diverse origin and presentation. A prominent feature of NET cells is the expression of G protein-coupled receptors called somatostatin receptors (SSTR). Although these SSTR are not uniformly present in NET, they can be instrumental in the diagnosis and treatment of NET. Apart from their application in nuclear imaging and radionuclide therapy, SSA have proven invaluable in the treatment of hormonal syndromes associated with certain NET (antisecretory effects of SSA), but it took more than two decades to convincingly demonstrate the antiproliferative effects of SSA in metastatic NET with the two pivotal studies PROMID and CLARINET. The current review summarizes three decades of SSA treatment and provides an overview of the clinical trial landscape for SSA monotherapy and combination therapy, including clinical implications and quality of life aspects, as well as ongoing fields of research.

Эффективность и безопасность пантопразола в лечении пациентов с кислотозависимыми заболеваниями в России: многоцентровое наблюдательное исследование

The aim – evaluate the clinical effect and adherence to pantoprazole (Nolpaza®) therapy in patients with acid-dependent diseases in real clinical practice. Pantoprazole occupies a special place among various representatives of proton pump inhibitors (PPI) due to the peculiarities of its pharmacokinetics and pharmacodynamics. Thus, the area under the curve (AUC), correlating with the severity of acid-suppressive effect, is significantly higher for pantoprazole than for other PPIs. In addition, pantoprazole has a longer-lasting antisecretory effect because it is the only PPI that binds to both cysteine 813 and deep-lying cysteine 822. Of all PPIs, pantoprazole least blocks the CYP2C19 isoenzyme involved in multidrug metabolism, ensuring minimal drug interactions. Material and methods. Data collection for further analysis was performed using specially designed electronic individual registration cards of two groups of patients: the first – patients with gastroesophageal reflux disease (GERD), receiving therapy with Nolpaza®; the second – patients with peptic ulcer disease (PU) / erosive gastritis and patients with an indication for Helicobacter pylori eradication, receiving therapy with Nolpaza® as part of the eradication therapy regimen. Conclusion. According to the results of the conducted study it was possible to evaluate the clinical effect and tolerability of Nolpaza® therapy using the data of more than 14 thousand patients with GERD, gastritis, duodenitis, gastric and duodenal ulcer, drug-induced gastropathy, 98% of whom had gastrointestinal complaints before the beginning of treatment, while by the end of therapy the complaints remained in full in less than 1% of patients. The results of esophagogastroduodenoscopy at the end of therapy with Nolpaza® confirmed positive dynamics in 99.8% of cases, and the vast majority of patients achieved complete endoscopic remission. Positive dynamics was also observed in the majority of patients who were tested for H. pylori infection. The efficacy of eradication therapy with Nolpaza® amounted to 88.2%. The study provided a high assessment of patient adherence throughout the follow-up period.

Gastric Ulcer Mechanism, Protection and Treatment from Natural Sources

Gastric acid secretions are main cause for formation of gastric ulcers that are attributed by Helicobacter pylori infection and extensive use of NSAIDs (non-steroidal anti-inflammatory drugs). These contributors facilitate the initiation of cellular and molecular signalling pathways in our body that give rise to formation of gastric ulcer. Generally, gastric ulcer results in minute to deep invading of gastric mucosal linings which may produce harmful symptoms in our body. Non-infectious gastric ulcers are another problem related with gastro-intestinal disorders that mainly caused because of poor daily activities including alcohol consumption, oxidative stress, mental stress and low consumption in healthy food intake. Stress plays a crucial role in the formation gastric ulceration due to its effect on the generation of ROS (reactive oxygen species) and RNS (reactive nitrogen species).Gastric cancer is found common in severe ulceration and gastric lesions. This type of cancer mainly attributed by untreated gastric ulcer and other related infected and inflammatory conditions. They all increase the worldwide incidence of morbidity and mortality rates. Therefore, a novel approach towards research and development has been must to categorise these complications. Natural agents with adaptogenic and antioxidant properties are useful in this situation. Some of the herbal extracts have been used from ancient times due to their cytoprotective, anti-inflammatory and antioxidant effects. New approaches are still on progress to obtain a potential phytopharmaceutical and natural agent to treat these disorders. It has been reported anti-secretory effects of herbal preparations give rise to protective action in the cure of gastric ulcers. We try to explain mechanisms involve in this complication and important pharmacological activity of natural extracts to counter act these symptoms in our review.

Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas

Cyclic nucleotide elevation in intestinal epithelial cells is the key pathology causing intestinal fluid loss in secretory diarrheas such as cholera. Current secretory diarrhea treatment is primarily supportive, and oral rehydration solution is the mainstay of cholera treatment. There is an unmet need for safe, simple and effective diarrhea treatments. By promoting cAMP hydrolysis, extracellular calcium-sensing receptor (CaSR) is a regulator of intestinal fluid transport. We studied the antidiarrheal mechanisms of FDA-approved CaSR activator cinacalcet and tested its efficacy in clinically relevant human cell, mouse and intestinal organoid models of secretory diarrhea. By using selective inhibitors, we found that cAMP agonists-induced secretory short-circuit currents (Isc) in human intestinal T84 cells are mediated by collective actions of apical membrane cystic fibrosis transmembrane conductance regulator (CFTR) and Clc-2 Cl− channels, and basolateral membrane K+ channels. 30 μM cinacalcet pretreatment inhibited all 3 components of forskolin and cholera toxin-induced secretory Isc by ∼75%. In mouse jejunal mucosa, cinacalcet inhibited forskolin-induced secretory Isc by ∼60% in wild type mice, with no antisecretory effect in intestinal epithelia-specific Casr knockout mice (Casr-flox; Vil1-cre). In suckling mouse model of cholera induced by oral cholera toxin, single dose (30 mg/kg) oral cinacalcet treatment reduced intestinal fluid accumulation by ∼55% at 20 hours. Lastly, cinacalcet inhibited forskolin-induced secretory Isc by ∼75% in human colonic and ileal organoids. Our findings suggest that CaSR activator cinacalcet has antidiarrheal efficacy in distinct human cell, organoid and mouse models of secretory diarrhea. Considering its excellent clinical safety profile, cinacalcet can be repurposed as a treatment for cyclic nucleotide-mediated secretory diarrheas including cholera.

Crucial role of carbon monoxide as a regulator of diarrhea caused by cholera toxin: Evidence of direct interaction with toxin

The present study evaluated the role of heme oxygenase 1 (HO-1)/carbon monoxide (CO) pathway in the cholera toxin-induced diarrhea and its possible action mechanism. The pharmacological modulation with CORM-2 (a CO donor) or Hemin (a HO-1 inducer) decreased the intestinal fluid secretion and Cl− efflux, altered by cholera toxin. In contrast, ZnPP (a HO-1 inhibitor) reversed the antisecretory effect of Hemin and potentiated cholera toxin-induced intestinal secretion. Moreover, CORM-2 also prevented the alteration of intestinal epithelial architecture and local vascular permeability promoted by cholera toxin. The intestinal absorption was not altered by any of the pharmacological modulators. Cholera toxin inoculation also increased HO-1 immunoreactivity and bilirubin levels, a possible protective physiological response. Finally, using fluorometric technique, ELISA assay and molecular docking simulations, we show evidence that CO directly interacts with cholera toxin, forming a complex that affects its binding to GM1 receptor, which help explain the antisecretory effect. Thus, CO is an essential molecule for protection against choleric diarrhea and suggests its use as a possible therapeutic tool.

Newer, Older, and Alternative Agents for the Eradication of Helicobacter pylori Infection: A Narrative Review.

Although discovered 40 years ago, Helicobacter pylori infection is still raising diagnostic and therapeutic problems today. The infection is currently managed based on statements in several guidelines, but implementing them in practice is a long process. Increasing antibiotic resistance and weak compliance of the patients limit the efficacy of eradication regimens, leaving much room for improvement. Third-generation proton pump inhibitors have added little to the results of the first two generations. Potassium-competitive acid blockers have a stronger and longer inhibitory action of acid secretion, increasing the intragastric pH. They obtained superior results in eradication when compared to proton pump inhibitors. Instead of innovative antibiotics, derivatives of existing antimicrobials were developed; some new fluoroquinolones and nitazoxanide seem promising in practice, but they are not recommended by the guidelines. Carbonic anhydrase inhibitors have both anti-secretory and bactericidal effects, and some researchers are expecting their revival in the treatment of infection. Capsules containing components of the eradication regimens have obtained excellent results, but are of limited availability. Probiotics, if containing bacteria with anti-Helicobacter pylori activity, may be useful, increasing the rates of eradication and lowering the prevalence and severity of the side effects.

How to Make the Right Choice of Proton Pump Inhibitor for Patients with Gastroesophageal Reflux Disease?

Аim: to analyze the main pharmacokinetic properties of proton pump inhibitors (PPIs) and their significance in the treatment of gastroesophageal reflux disease (GERD).Key points. Pantoprazole has a high bioavailability, the absolute bioavailability of pantoprazole at a dose of 40 mg is 77 % from the first dose and does not change with repeated use. Pantoprazole shows a faster onset of action than omeprazole. Simultaneous food intake does not change the bioavailability of pantoprazole. Suppression of hydrochloric acid production while taking pantoprazole accompanies by the achievement of endoscopic remission of GERD by day 28 in 91 % of patients with reflux esophagitis and by day 56 in all patients in the PANSTAR studies. Pantoprazole has little effect on CYP2C19 compared to other PPIs, minimizing the risk of drug-drug interactions. Pantoprazole is the most pH-selective PPI, which determines the specificity of action only in the parietal cells of the stomach and the greatest safety of long-term use in patients with comorbid pathology.Conclusion. PPIs form the basis of the therapy of acid-dependent diseases, and, in particular, gastroesophageal reflux disease. Pantoprazole is distinguished from other PPIs by its persistent high bioavailability, long-term antisecretory effect, and very low affinity for cytochrome P450.

Antiulcer activity of hydroalcoholic extract of Bombacopsis glabra (Pasq.) A. Robyns. Leaves (Bombacaceae) in rat

The purpose of this study was to investigate the activity of the hydroalcoholic extract ofBombacopsis glabra leaves in rat. The mucoprotector effect of B. glabra leaves hydroalcoholic extract was studied by evaluating its ability to protect the mucosa from aggression of repeated oral administration of indomethacin at a dose of 30 mg/kg while pylorus ligature was used to study its anti-secretory effect. The results show that hydroalcoholic extract of the leaves of B. glabra, at doses 300 and 600mg/kg, decrease the surface area of lesions induced by indomethacin from 6.2 observed in the control group animals to 2.51 and 1.19 0.073 mm² respectively, in the treated animals (p 0.05). The extract decreases gastric acidity by increasing the pH of the gastric content from 1.7 0.03 of the control animals to 2.27 3.59 0.11 of the animals that received the extract at dose 300 and 600mg/kg respectively (p&lt;0.05). These results show that the hydroalcoholic extract of B. glabra leaves possesses an anti-secretory effect and acts as a mucoprotector, and therefore has an antiulcer activity. The alkaloids, flavonoids, tannins, or polysaccharides in the extract could be responsible for this activity.

Probiotic Properties of Saccharomycetes (Review)

The purpose of the review is to summarize and analyze information on the molecular genetic basis and methods for studying the probiotic activity of Saccharomycetes fungi, the mechanisms of their physiological action, and their application in biotechnology. The relevance of research in this area is confirmed by the dynamics of the growth of publications. The effectiveness of Saccharomyces boulardii in the treatment and prevention of diarrhea of various etiologies, relapses of C. difficile infection, side effects of H. pylori infection therapy has been established with a high level of evidence. Genetic, cytological, cultural and biochemical features of S. boulardii determine their probiotic activity. Other Saccharomyces strains with probiotic potential are most often isolated from national fermented plant and dairy products. A unified methodology for studying the probiotic properties of yeast has not yet been created; clinical trials involving people are needed to confirm their status. Promising probiotics are strains of the species S. cerevisiae and K. marxianus, which have an international safety status. Possible mechanisms of physiological action of Saccharomycetes include antimicrobial and antitoxic, trophic, antisecretory and anti-inflammatory effects. Some of the mechanisms of yeast probiotic action differ from those of bacteria, and not all of them are yet understood. Saccharomycetes probiotics can be used to improve the biological value, quality and safety of food products.

Mechanistic insights of Cucumis melo L. seeds for gastrointestinal muscle spasms through calcium signaling pathway–related gene regulation networks in WGCNA and in vitro, in vivo studies

BackgroundIn addition to the nutritional benefits of Cucumis melo L., herbalists in Pakistan and India employ seeds to treat various ailments. This study aimed to determine the regulatory role of C. melo seeds in calcium-mediated smooth muscle contraction. MethodsWe identified and quantified the phytochemicals of C. melo with LC ESI–MS/MS and HPLC, then conducted in vitro and in vivo tests to confirm the involvement in smooth muscle relaxation. Then, diarrhea-predominant irritable bowel syndrome gene datasets from NCBI GEO were acquired, DEGs and WGCNA followed by functional enrichment analysis. Next, molecular docking of key genes was performed. ResultsThe quantification of C. melo seeds revealed concentrations of rutin, kaempferol, and quercetin were 702.38 μg/g, 686.29 μg/g, and 658.41 μg/g, respectively. In vitro experiments revealed that C. melo seeds had a dose-dependent relaxant effect for potassium chloride (80 mM)–induced spastic contraction and exhibited calcium antagonistic response in calcium dose-response curves. In in vivo studies, Cm.EtOH exhibited antidiarrheal, antiperistaltic, and antisecretory effects. The functional enrichment of WGCNA and DEGs IBS-associated pathogenic genes, including those involved in calcium-mediated signaling, MAPK cascade, and inflammatory responses. MAPK1 and PIK3CG were identified as key genes with greater binding affinity with rutin, quercitrin, and kaempferol in molecular docking. ConclusionsThe bronchodilator and antidiarrheal effects of C. melo were produced by altering the regulatory genes of calcium-mediated smooth contraction.

Super-resolution 3D maps to study the antisecretory factor's effects on different GABAa receptor subunits in rat cerebellar granule cells in vitro.

The Antisecretory Factor (AF) is an endogenous protein that inhibits intestinal hypersecretion and various inflammation disorders in vivo. AF has been detected in many mammalian tissues and plasma, but its mechanisms of action are essentially unknown. Previously, we studied the pharmacological action of the AF on GABAA receptors in cerebellar granule cells, comparing the electrophysiological response evoked by two-photon mediated release of caged GABA compounds before and after the administration of AF-16, a 16 amino acids long peptide obtained from the amino-terminal end of the AF protein. After the treatment with AF-16, we observed an increase in the GABAA receptor responses, particularly in those containing the α6 subunit. To figure out the interactions of AF with GABAA receptors in the same cellular model (cerebellar granule cells), we combined immunofluorescence subunits’ staining with confocal and super-resolution microscopy. In particular, we took advantage of an innovative imaging technique that combines stimulated emission depletion (STED) with fluorescence lifetime microscopy (FLIM) to collect super-resolution 3D maps of different subunits distributed on the neuron cell membrane. We explored different approaches to analyze super-resolution fluorescence images obtained by labeling α1 and α6 subunits before and after 1-hour incubation with AF-16. Comparing pre- and post-treatment maps, we found differences in how different subunit populations respond to AF treatment. We critically analyzed these new experimental findings with our previous electrophysiological data to widen the knowledge of the mechanisms of interaction between GABAA receptor subunits and AF protein.

Piperine as potential therapy of post-weaning porcine diarrheas: an in vitro study using a porcine duodenal enteroid model

Post-weaning diarrhea in piglets is a major problem, resulting in a significant loss in pig production. This study aimed to investigate the effects of piperine, an alkaloid abundantly found in black peppers, on biological activities related to the pathogenesis of post-weaning diarrhea using a porcine duodenal enteroid model, a newly established intestinal stem cell-derived in vitro model recapitulating physiology of porcine small intestinal epithelia. Porcine duodenal enteroid models were treated with disease-relevant pathological inducers with or without piperine (8 μg/mL and/or 20 μg/mL) before measurements of oxidative stress, mRNA, and protein expression of proinflammatory cytokines, nuclear factor-kappa B (NF-κB) nuclear translocation, barrier leakage, and fluid secretion. We found that piperine (20 μg/mL) inhibited H2O2-induced oxidative stress, TNF-α-induced mRNA, and protein expression of proinflammatory cytokines without affecting NF-κB nuclear translocation, and prevented TNF-α-induced barrier leakage in porcine duodenal enteroid monolayers. Importantly, piperine inhibited fluid secretion induced by both forskolin and heat-stable toxins (STa) in a three-dimensional model of porcine duodenal enteroids. Collectively, piperine possesses both anti-inflammatory and anti-secretory effects in porcine enteroid models. Further research and development of piperine may provide novel interventions for the treatment of post-weaning porcine diarrhea.

Toxicology of rabeprazole: a literature survey and an in silico study

Rabeprazole (RPZ), a widely used gastric proton pump inhibitor, is evidently toxic to humans. This study aims to sketch a current scenario of its toxicological impacts on humans or other animals on the basis of database reports. Additionally, an in silico study has also been performed to integrate its toxicological prospects as observed in databases. For this, an up-to-date (till March 2023) search was made in a number of databases to obtain the published literature with the specific keywords. Findings suggest that RPZ has many side effects, including nausea, vomiting, diarrhea, headache, rhinitis, myalgia, pharyngitis, abdominal pain, dyspepsia, eye disorders, and so on. Chronic exposure to RPZ causes some important biochemical and hematological alterations and exerts a number of toxicological effects (e.g., hypergastrinaemia, hyperplasia, atrophy of the gastric glands, gastric anti-secretory effect, hypochlorhydria) in humans. The in silico study suggests that RPZ has hepatotoxic and carcinogenic effects. Its AMES toxicity may lead to mutagenicity in humans. In conclusion, RPZ and its formulations have many toxicological impacts on humans and other animals. Adequate precautions should be taken during its long-term use.