Antisecretory Effect Research Articles

Ameliorative effects of ribes rubrum oil against gastric ulcers caused by indomethacin in experimental models

The objective of this study was to assess the anti-inflammatory effects of ribes rubrum oil at three different doses (5, 10 and 15 ml/kg b.w/day) in adult male albino rats with indomethacin-induced stomach ulcers (IND). Forty rats (135 ± 5 g) categorized into 5 groups (n = 8), for 45 days. Group (1) normal control, thirty-two rats were gavaged IND as single oral dose (30 mg/Kg b.w) resulted in gastric ulcer, then distributed to four groups, group (2) IND-intoxicated control, Groups 3, 4 and 5 were administrated ribes rubrum oil at levels of (5, 10 & 15 ml/kg b.w) respectively. Administrated levels of ribes rubrum oil found to have remarkable elevation in food conversion efficiency in experimental rats, gastric juice pH, in compared to the drunken control group, gastric prostaglandin E2 and gastric cytochrome P450 reductase levels were lower. The levels of pro-inflammatory cytokines NO, TNF-, and IL-1 were dramatically reduced, which was related with an increase in blood hemoglobin (Hb), packed cell volume (PCV), and red blood cells (RBCs)in ulcerogenic rats compared to intoxicated control. Data showed that, the main components of ribes rubrum oil are β-Pinene, γ-linolenic and Linalool oxide levels (25.9%, 23.10% and 10.5%, respectively) for their antioxidant activity. Findings showed that administrate ribes rubrum oil at dose 15 ml/kg followed by 10 ml/kg had the best results against ulcerogenic rats. In conclusion, the outcomes are consistent with the concept that ribes rubrum oil had a gastroprotective and antisecretory effects against gastric ulcer that may be attributed to the antioxidant properties of the oil that ameliorates the damage occur in gastric of rats.

Antisecretory Effect of the Combination of Pegagan (Centella Asiatica) and Sambiloto (Andrographis paniculata) Leaves Ethanol Extracts on Pyloric Ligation-Induced Gastric Ulcer in Rats

a peer-reviewed, open access online international journal which publishes original research papers. The journal welcomes submission from scholars and experts for possible publication from all over the world. The scope of the journal includes: Pharmaceutical research, chemistry and biochemistry of naturally occurring compounds, biological evaluation of crude extracts, ethnomedicine, traditional and complementary medicine, ethnopharmacology, biomedical research, Biotechnology, Evaluation of natural substances of land and sea and of plants, microbes and animals, pharmacognosy, bioavailability, clinical, pharmacological, toxicological studies and pharmacokinetics of phytochemicals, Isolation and characterization of compounds, structure elucidation, synthesis and experimental biosynthesis of natural Product as well as developments of methods in these areas are welcomed in the journal.

Propolis and Its Gastroprotective Effects on NSAID-Induced Gastric Ulcer Disease: A Systematic Review

Gastric ulcer disease induced by the consumption of NSAIDs is a major public health problem. The therapy used for its treatment causes adverse effects in the patient. Propolis is a natural product that has been used for the treatments of different diseases around the world. Nevertheless, there is little information about the activity of propolis in gastric ulcers caused by treatment with NSAIDs. Therefore, this review evaluates and compares the gastroprotective potential of propolis and its function against NSAID-induced gastric ulcers, for which a systematic search was carried out in the PubMed and ScienceDirect databases. The main criteria were articles that report the gastroprotective activity of propolis against the damage produced by NSAIDs in the gastric mucosa. Gastroprotection was related to the antioxidant, antisecretory, and cytoprotective effects, as well as the phenolic compounds present in the chemical composition of propolis. However, most of the studies used different doses of NSAIDs and propolis and evaluated different parameters. Propolis has proven to be a good alternative for the treatment of gastric ulcer disease. However, future studies should be carried out to identify the compounds responsible for these effects and to determine their potential use in people.

Количественный анализ скорости антисекреторного эффекта комбинированного ингибитора протонной помпы Эзолонг

Актуальность. Лечение кислотозависимых заболеваний является актуальной проблемой современной гастроэнтерологии, что обусловлено широким распространением этой группы нозологий в структуре заболеваний желудочно-кишечного тракта. Ведущее место в лечении этих заболеваний занимают ингибиторы протонной помпы. Критериями их выбора является время начала действия, выраженность и длительность кислотосупрессии, устойчивость эффекта в течение суток, наличие различных дозировок препарата. Именно поэтому в последние годы предпочтение отдается комбинированным препаратам. Сейчас в Украине используется новое поколение комбинированных средств, представителем которых является Эзолонг. Это лекарственное средство, которое кроме высококачественного эзомепразола (в дозировке 20 или 40 мг) содержит еще и антацид в виде натрия гидрокарбоната (1080 мг). Именно это сочетание делает данный препарат уникальным. Цель: определить скорость воздействия комбинированного препарата Эзолонг (эзомепразол 40 мг + натрия гидрокарбонат 1080 мг) на состояние желудочной кислотопродукции и степень ее ингибирования при использовании разовой дозы препарата. Материалы и методы. Под наблюдение было взято 20 пациентов с различными формами хронического гастродуоденита. Уровень кислотопродукции оценивался с помощью внутрижелудочного рН-мониторинга с применением ацидографа АГ-1. Далее больные получали разовую дозу Эзолонга (40 мг) и находились под наблюдением в течение 3 часов. Результаты. Проанализировав скорость антисекреторного действия разовой дозы Эзолонга, выявили, что у большинства больных (95 %) прием данного препарата приводит к повышению уровня интрагастрального рН до гипоацидных цифр (от 3,0 до 7,8), у некоторых пациентов отмечаются даже анацидные значения рН. Доказано, что для Эзолонга характерно быстрое начало действия (в среднем 6 минут) и достоверное повышение рН до выраженной гипо­ацидности. Выводы. Прием Эзолонга обеспечивает активное, мощное и длительное подавление желудочной кислотопродукции, является эффективным и безопасным при лечении кислотозависимых заболеваний.

Herbal Medicines in the Treatment of Dyspepsia: An Overview

This review focuses on the efficacy of herbal medicines for managing dyspepsia in humans and animals. Searches were conducted on the PubMed, Science Direct, and Medline databases, for publications in the last 3 years. In each database, the search terms used consisted of the 2 key terms describing the disorder and subtypes plus each of the terms relating to the therapy. The key terms used were "natural product" and "medicinal plant" in a cross-over with "dyspepsia" and "functional dyspepsia" (i.e., gastroprotection, Helicobacter pylori infection, prokinetic). We included all human and animal studies on the effects of herbal medicines reporting the key outcome of dyspepsia symptoms. Preclinical studies using critically validated models showed that most medicinal plants with gastroprotective action had antioxidant, anti-inflammatory, anti-apoptotic, and antisecretory effects. Moreover, several species displayed anti Helicobacter pylori and prokinetic efficacy. The data availability of controlled clinical studies is currently minimal. The use of different methodologies and the minimal number of patients raise doubts about the effects of these preparations. Only adequate clinical trials with scientifically validated methods can determine whether different herbal medicines can be used as viable alternatives to the conventional pharmacological treatments used to control dyspepsia symptoms.

β-eudesmol but not atractylodin exerts an inhibitory effect on CFTR-mediated chloride transport in human intestinal epithelial cells

Oriental herbal medicine with the two bioactive constituents, β-eudesmol (BE) and atractylodin (AT), has been used as a remedy for gastrointestinal disorders. There was no scientific evidence reporting their antidiarrheal effect and underpinning mechanisms. Therefore, we aimed to investigate the anti-secretory activity of these two compounds in vitro. The inhibitory effect of BE and AT on cAMP-induced Cl- secretion was evaluated by Ussing chamber in human intestinal epithelial (T84) cells. Short-circuit current (ISC) and apical Cl- current (ICl-) were measured after adding indirect and direct cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activator. MTT assay was used to determine cellular cytotoxicity. Protein-ligand interaction was investigated by in silico molecular docking analysis. BE, but not AT concentration-dependently (IC50 of ~1.05 µM) reduced cAMP-mediated, CFTRinh-172 inhibitable Cl− secretion as determined by transepithelial ISC across a monolayer of T84 cells. Potency of CFTR-mediated ICl- inhibition by BE did not change with the use of different CFTR activators suggesting a direct blockage of the channel active site(s). Pretreatment with BE completely prevented cAMP-induced ICl-. Furthermore, BE at concentrations up to 200 µM (24 h) had no effect on T84 cell viability. In silico studies indicated that BE could best dock onto dephosphorylated structure of CFTR at ATP-binding pockets in nucleotide-binding domain (NBD) 2 region. These findings provide the first evidence for the anti-secretory effect of BE involving inhibition of CFTR function. BE represents a promising candidate for the therapeutic or prophylactic intervention of diarrhea resulted from intestinal hypersecretion of Cl-

Mechanism of preservation of the intestinal mucosa architecture and NF-κB/PGE2 reduction by hydrogen sulfide on cholera toxin-induced diarrhea in mice

AimsInvestigate the involvement of Hydrogen sulfide (H2S) in inflammatory parameters and intestinal morphology caused by cholera toxin (CT) in mice. Main methodsMice were subjected to the procedure of inducing diarrhea by CT in the isolated intestinal loop model. The intestinal loops were inoculated with H2S donor molecules (NaHS and GYY 4137) or saline and CT. To study the role of EP2 and EP4 prostaglandin E2 (PGE2) receptors in the H2S antisecretory effect, PAG (DL-propargylglycine - inhibitor of cystathionine-γ-lyase (CSE)), PF-04418948 (EP2 antagonist) and ONO-AE3-208 (EP4 antagonist) were used. The intestinal loops were evaluated for intestinal secretion, relation of the depth of villi and intestinal crypts, and real-time PCR for the mRNA of the CXCL2, IL-6, NOS-2, IL-17, NF-κB1, NF-κBIA, SLC6A4 and IFN-γ genes. Key findingsH2S restored the villus/crypt depth ratio caused by CT. NaHS and GYY 4137 increased the expression of NF-κB1 and for the NF-κBIA gene, only GYY 4137 increased the expression of this gene. The increased expression of NF-κB inhibitors, NF-κB1 and NF-κBIA by H2S indicates a possible decrease in NF-κB activity. The pretreatment with PAG reversed the protective effect of PF-04418948 and ONO-AE3-208, indicating that H2S probably decreases PGE2 because in the presence of antagonists of this pathway, PAG promotes intestinal secretion. SignificanceOur results point to a protective activity of H2S against CT for promoting a protection of villus and crypt intestine morphology and also that its mechanism occurs at least in part due to decreasing the activity of NF-κB and PGE2.

Evaluation of antidiarrheal effect of combination of Salam Leaves (Syzygiumpolyanthum) and Jackfruit Leaves (Artocarpus heterophyllus Lam.) infusum in rats induced by castor oil


 Backround: Diarrhoea is a condition characterised by watery, loose stools that occurs more than three times daily. In Indonesian traditional medicine, salam leaves and jackfruit leaves have been used as herbal treatments for many conditions, including as antidiarrheal medicines. 
 Aims: The aim of this experimental study was to evaluate the antidiarrheal effect of a combination of Salam leaves and jackfruit leaves infusum induced by castor oil in rats. 
 Method: The rats were divided into nine groups, where the negative control group was given CMC 1 %, the positive control group was given tannins, and five test groups were given the infusum with five comparisons of each dose administered orally. Castor oil was used as a stimulant of diarrhoea. 
 Results: The results show that with all combinations of salam leaves: jackfruit leaves have antidiarrheal effects with decreased frequency of defecation, faeces consistency, and faeces weight at ratios of 1:1, 1:2, 1:3, 2:1, and 3:1 compared to the negative control (p < 0.05). Phytochemical test of the infusum indicated positive tannins. The antidiarrheal effect of both infusums might be due to the presence of tannins, which have anti-secretory effect in the intestinal lumen. 
 Conclusions: The treatment with combination of salam leaves and jackfruit leaves infusum in rats induced by Castor oil has an antidiarrheal effect. The best result is a mixture of salam infusum: jackfruit infusum with 3:1 ratio.

Evaluation of In Vivo Antiulcer Activity of Hydro-Methanol Extract and Solvent Fractions of the Stem Bark of Ficus thonningii (Moraceae) on Rodent Models.

Introduction The stem bark of Ficus thonningii is used by Ethiopian traditional healers and the community for the treatment of peptic ulcer disease. Thus, the current study was aimed at evaluating the antiulcer effect of hydro-methanol extract and solvent fractions of F. thonningii. Methods The stem bark of F. thonningii was collected and shed dried. Then, the stem bark was extracted by 80% hydro-methanol solvents and dried. The part of the dried hydro-methanol extract was further fractionated with n-hexane, chloroform, and distilled water. Dose-dependent pylorus ligation, curative indomethacin-induced, and time-dependent ethanol-induced ulcer models were evaluated for the hydro-methanol extract and solvent fractions. Statistical analysis was done by using the Statistical Package for the Social Sciences (SPSS) version 24. The analyses were carried out using one-way analysis of variance (ANOVA), followed by Tukey's multiple comparison tests. The result was considered significant when p < 0.05. Results The extract of F. thonningii showed a significant (p < 0.001) reduction in total acidity at all the tested doses (100, 200, and 400 mg/kg). All the tested doses of the hydro-methanol extract significantly reduced the gastric volume as compared to the vehicle (NC) (p < 0.01). The gastric pH was significantly (p < 0.05) increased by 200 and 400 mg/kg. Similarly, 200 mg/kg and 400 mg/kg significantly (p < 0.05) lowered gastric ulceration as compared to the NC. The hydro-methanol extract and aqueous fractions of F. thonningii at 200 mg/kg showed significant (p < 0.05) reduction in the ulcer index on a repeated dose of the hydro-methanol and solvent fractions. Ulcer healing effect on indomethacin-induced ulcer was not significant (p > 0.05) for all tested doses of the hydro-methanol extract. Conclusion The study demonstrated that the stem bark of F. thonningii has a potential antiulcer activity that might be due to antisecretory or cytoprotective effects.

Effects of CYP2C19 Polymorphism on Metabolism and Effectiveness of Proton Pump Inhibitors: A Review of Clinical and Laboratory Studies

Introduction: Establishing the reasons for the decrease in the effectiveness of anti-Helicobacter pylori therapy and proton pump inhibitors in the treatment of acid-dependent diseases is an urgent task due to high prevalence of these disorders undermining population health. Our objective was to conduct a literature review to assess the influence of the genetic polymorphism of cytochrome P-450 CYP2C19 on the eradication rate of Helicobacter pylori and the metabolism of proton pump inhibitors, to evaluate the effectiveness of their use, and to determine possible ways of overcoming refractoriness to these drugs in the clinic. Materials and methods: We analyzed published studies found in domestic (eLibrary, CyberLeninka.ru) and international (PubMed, Cochrane Library) databases. Results: We revealed a genetic polymorphism CYP2C19 of cytochrome P-450, according to which different types of drug metabolism were identified: fast, intermediate, slow, and ultrafast. The relationship of this polymorphism with biotransformation of proton pump inhibitors was then analyzed. In Russia, the predominance of fast and intermediate metabolism in individuals of the Caucasian race decreases the efficacy of acid-suppressive therapy and the Helicobacter pylori eradication rate. Correction of the daily dose and frequency of drug administration are necessary to increase the antisecretory effect of proton pump inhibitors. Discussion: The dependence of proton pump inhibitor biotransformation on the CYP2C19 polymorphism determines the differences between patients with different types of metabolism in the effectiveness of these drugs, the success of anti-Helicobacter pylori treatment, and clinical outcomes. Pharmacogenetic testing is useful for predicting the response to proton pump inhibitors, the likelihood of developing adverse events, and the possibility of personalized prescriptions in patients with acid-related diseases. Conclusion: Genetic testing of cytochrome CYP2C19 helps optimize the use of proton pump inhibitors, overcome refractoriness, and improve the quality of treatment of acid-dependent diseases and the overall Helicobacter pylori eradication rate.

Tablet of Spondias mombin L. Developed from Nebulized Extract Prevents Gastric Ulcers in Mice via Cytoprotective and Antisecretory Effects.

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.

Effects of Cola anomala (K. Schum.) water/ethanol pods extract on the inflammation and intestinal secretion in lipopolysaccharide-induced diarrhea

Diarrhea is one of the leading causes of death among children in low and low-middle income countries and the management of this pathology is still a problem in these regions. The water/ethanol extract of the pods of Cola anomala (KEO) has been shown to possess antimicrobial and antidiarrheal effects in Shigella flexneri-induced diarrhea, but whether KEO is active on the toxemic part of this diarrhea is unknown. This study was undertaken to evaluate the effects of KEO on the intestinal secretion and inflammation induced by intraperitoneal administration of lipopolysaccharide (LPS). KEO obtained by maceration in water/ethanol (1:1) was administered orally (25, 50 and 100 mg/kg of body weight) against LPS-induced diarrhea in mice. The mass of feces, the intestinal nitric oxide (NO) and prostaglandin (PGE2) contents as well as myeloperoxidase (MPO) activity were assessed. KEO was also tested on LPS-induced enteropooling in rats. In this experiment, the intestinal fluid and its electrolytes (Na+, K+ and Cl-) contents were determined as well as NO, PGE2, TNF-α and IL-1β levels in the small intestine homogenate. Indomethacin (5 mg/kg) was used as reference drug. KEO significantly (p &lt; 0.001) reduced stools excretion, NO content and MPO activity in intestine but did not affect PGE2 in LPS-induced diarrhea. On the enteropooling model, KEO showed no effect on the intestinal fluid and electrolyte excretion, PGE2, TNF-α and IL-1β contents, but significantly (p &lt; 0.05) reduced the NO production. This study suggests that KEO does not have antisecretory effect, but has anti inflammatory activities. It can be concluded that the anti-toxemic effect of KEO contributes less to its antidiarrheal activity in infectious diarrhea.

TGF-β1/Smad2/3 signaling pathway modulates octreotide antisecretory and antiproliferative effects in pituitary somatotroph tumor cells.

Octreotide (OCT) is used to inhibit hormone secretion and growth in somatotroph tumors, although a significant percentage of patients are resistant. It has also been tested in nonfunctioning (NF) tumors but with poor results, with these outcomes having been associated with SSTR2 levels and impaired signaling. We investigated whether OCT inhibitory effects can be improved by TGF-β1 in functioning and nonfunctioning somatotroph tumor cells. OCT effects on hormone secretion and proliferation were analyzed in the presence of TGF-β1 in WT and SSTR2-overexpressing secreting GH3 and silent somatotroph tumor cells. The mechanism underlying these effects was assessed by studying SSTR and TGFβR signaling pathways mediators. In addition, we analyzed the effects of OCT/TGF-β1 treatment on tumor growth and cell proliferation in vivo. The inhibitory effects of OCT on GH- and PRL-secretion and proliferation were improved in the presence of TGF-β1, as well as by SSTR2 overexpression. The OCT/TGF-β1 treatment induced downregulation of pERK1/2 and pAkt, upregulation of pSmad3, and inhibition of cyclin D1. In vivo experiments showed that OCT in the presence of TGF-β1 blocked tumor volume growth, decreased cell proliferation, and increased tumor necrosis. These results indicate that SSTR2 levels and the stimulation of TGF-β1/TGFβR/Smad2/3 pathway are important for strengthening the antiproliferative and antisecretory effects of OCT.

Gastric H+, K+-ATPase inhibitory effects of the active constituent isolated from Potentilla fulgens roots: An in vivo and in silico molecular docking studies

Background and objectivePotentilla fulgens (Rosaceae) is an edible medicinal herb which is widely used in Indian and Chinese traditional medicine for treating gastric ulcer, diabetes, cancer and diarrhea. Literature reveals that the crude ethanolic extract (EPF) of the plant possessed promising gastroprotective effects in rodents. However, the actual chemical marker with a probable mechanism of action responsible for its anti-secretory efficacy is still left unexplored. Hence, the present investigation was aimed to examine the phytoconstituents responsible for gastric anti-secretory effect incorporating in vivo study supported by in silico molecular docking techniques. MethodsExperimentally, four EPF bioactive fractions were tested viz. chloroform (PFCH), ethylacetate (PFEA), n-butanol (PFBu) and aqueous (PFAq). As per the bioactivity guided assay, the most bioactive fraction (PFEA) was subjected to column chromatography and the isolated component (-) epicatechin (EC) was screened for its effects on gastric ulceration induced by pyloric ligation (PL) and absolute ethanol. Various gastric secretion parameters such as gastric juice volume, pH, H+, K+-ATPase activity and histamine levels were determined. In silico molecular docking study was performed to predict the binding efficacy of EC responsible for the inhibition of H+, K+-ATPase enzyme. ResultsResults from the PL model indicate that PFEA, PFBu and EC showed significant gastroprotective effect (p<0.05) when compared to the ulcer control group with percentage protection of 70.16%, 55.39% and 67.00% respectively. The mechanism of action underlying the anti-secretory effect was attributed to EC (20 mg/kg, p.o.) that showed significant (p<0.05) decrease in gastric juice volume and H+, K+-ATPase activity. In silico studies revealed that EC exhibit promising inhibitory effect (binding energy of −8 kcal/mol) towards H+, K+-ATPase. This may be due to higher number of H-bond interactions (with Asp 137, Val 341, Glu 795 and Leu 811) and π-π stacking (with Tyr 799) with the amino acids of active site of H+, K+-ATPase. ConclusionThus, the present study indicates that the mechanism of gastroprotective activity of EC is attributed towards the potassium competitive acid blocker.

Pharmacological profile and effects of mitotane in adrenocortical carcinoma.

Mitotane is the only adrenolytic drug approved by the Food and Drug Administration for treating adrenocortical carcinoma (ACC). This drug has cytotoxic effects on tumour tissues; it induces cell death and antisecretory effects on adrenal cells by inhibiting the synthesis of adrenocortical steroids, which are involved in the pathogenesis of ACC. However, high doses of mitotane are usually necessary to reach the therapeutic plasma concentration, which may result in several adverse effects. This suggests that important pharmacological processes, such as first pass metabolism, tissue accumulation and extensive time for drug elimination, are associated with mitotane administration. Few studies have reported the pharmacological aspects and therapeutic effects of mitotane. Therefore, the aim of this review was to summarize the chemistry, pharmacokinetics and pharmacodynamics, and therapeutic and toxic effects of mitotane. This review also discusses new perspectives of mitotane formulation that are currently under investigation. Understanding the pharmacological profile of mitotane can improve the monitoring and efficacy of this drug in ACC treatment and can provide useful information for the development of new drugs with specific action against ACC with fewer adverse effects.

Differentiated approach to the choice of PPI in a patient with GERD in the practice of an outpatient (with a clinical case)

Gastroesophageal reflux disease (GERD) is a widespread disease. Despite the fact that different approaches to the treatment and prevention of recurrence of this disease have been developed, the number of patients with GERD, including refractory form of GERD, is only increasing. To date, well studied and described the possible links of the pathogenesis of this disease, which predetermine certain approaches to the treatment of various variants of GERD. Effective drug therapy of GERD includes the appointment of proton pump inhibitors (PPI). However, doctors are often faced with the problem of ineffective use of PPI in patients with GERD or with the so-called refractory form of GERD. The reasons for the ineffectiveness of therapy of PPI can be associated not only with the pathogenetic features of GERD and therapy, but also with the patient himself. Daily pH monitoring allows to determine the cause of the ineffectiveness of the treatment of PPI if the patient complies with all prescriptions. With ineffective acid suppression in the stomach, it is necessary to increase the dose of PPI or replace it. It is important to prescribe both effective and safe means of correcting the symptoms of GERD, and also take into account the possibility of long-term maintenance of remission when using them. These requirements are met by PPI, created in the form of enantiomers, having an improved pharmacokinetic profile. An example of this differentiated approach is dexlansoprazole, a law-converting monoisomer of lansoprazole with double release technology and the ability to maintain the antisecretory effect for a long time, which appeared relatively recently on the Russian pharmaceutical market. The use of this drug is presented in a clinical case.

Antisecretory Effect of Centella Asiatica Leaves Ethanolic Extract against Pyloric Ligation Induced Gastric Ulcers on Rats

Antisecretory Effect of Centella Asiatica Leaves Ethanolic Extract against Pyloric Ligation Induced Gastric Ulcers on Rats

Vonoprazan in the management of erosive oesophagitis and peptic ulcer-induced medication: a systematic review.

IntroductionVonoprazan has been found to promote a better antisecretory effect addressing acid-related diseases’ unmet needs.AimTo assess if vonoprazan effectively treats patients diagnosed with gastroesophageal reflux disease esophagitis or with peptic ulcers induced by chronic use of aspirin or non-steroidal anti-inflammatory drugs.Material and methodsA literature search was conducted (April/2021) using Medline via PubMed, Cochrane library, Lilacs, Scielo, and Centre for Reviews and Dissemination electronic databases.ResultsWe retrieved 55 titles. Of these, 13 met the eligibility criteria and were included in this review. Of these 13 articles, 4 were prospective cohort studies, 1 was a follow-up analysis of a preceding prospective study, 1 was a retrospective cohort study, and 6 were randomized clinical trials.ConclusionsOur findings suggest that vonoprazan was effective and non-inferior to proton pump inhibitors in healing and maintaining healed reflux oesophagitis, leading to faster symptom relief. Vonoprazan may also be considered for preventing aspirin- or non-steroidal anti-inflammatory drug-related peptic ulcer recurrence.

Deprescribing and Optimal Selection of Proton Pump Inhibitors (Contributions of the 26th United Russian Gastroenterology Week)

Aim. Presentation of the Forum “Deprescribing and optimal selection of proton pump inhibitors” held in Moscow on 29 September 2020 during the 26th United Russian Gastroenterology Week.Key points. The Forum was aimed at discussing issues associated with improving the proton pump inhibitor (PPIs) therapy in treatment and prevention of acid-related diseases and upper gastrointestinal tract (GIT) disorders induced by non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelet medications. Deprescribing is considered to be an effective strategy of a motivated reduction of the PPI dosage, duration of therapy and the patient’s transfer from a regular to on-demand intake regimen. The choice of PPI may condition an optimal therapy for acid-related diseases.Conclusion. PPIs prevail in therapies for acid-related diseases and NSAID-induced upper GIT lesions. PPI deprescribing should be a strategy of choice if medically indicated. A non-enzymatic metabolism, high acid suppression, stable antisecretory effect from day 1 of therapy and cytoprotective action justify the application of rabeprazole (Pariet®) for optimising therapies for acid-related diseases and implementing the deprescribing strategy.

Safety, Tolerability and Pharmacokinetics of Single Ascending and Multiple Oral Doses of Tegoprazan in Healthy Chinese Subjects

Tegoprazan is one of the potassium-competitive acid blockers (P-CABs). It exhibits its anti-secretory effects by competitively and reversibly blocking the availability of K+ of the H+, K+-ATPase. This study was designed to investigate the safety and pharmacokinetics of tegoprazan in healthy Chinese subjects. Thirty-eight healthy Chinese subjects were recruited in this randomized, single-center, double-blind, placebo-controlled study, with a single ascending dose of 50, 100, 200 mg and a multiple dose of 100 mg for 10 days. The plasma concentration of tegoprazan was determined by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetics were evaluated via non-compartmental and compartmental model analysis. Safety was assessed by physical examinations, vital signs, clinical laboratory tests, and electrocardiograms. No serious adverse event was observed in this study. After single-dose administration (50, 100 and 200 mg), tegoprazan was rapidly absorbed with a median maximum measure plasma concentration (Tmax) at 0.5h and declined with a terminal (elimination) half-life (t1/2) of 3.87-4.57h. The maximum measured plasma concentration (Cmax) for tegoprazan was 813.80, 1494.60 and 2829.00 ng/mL. Meanwhile, the correspondingarea under the concentration-time curve (AUC)from time zero to infinity (AUC0-inf)was 2761.00, 5980.05 and 11,044.72 ng∙h/mL in 50, 100, 200 mg group, respectively. Dose-dependent increase was observed in the value of Cmax and AUC after administration of tegoprazan 50 to 200 mg. The two-compartment model well described the pharmacokinetic profile of tegoprazan. In the steady state, no accumulation was found after repeated administration at the 100-mg dose level. No experimental differences were found based on gender. Tegoprazan was well tolerated in the dose range of 50-200 mg in single- and 100 mginmultiple-dose studies. Tegoprazan shows dose linearity with oral administration after a single dose of 50 to 200 mg and less drug accumulation after 10 days of continuous administration in 100 mg.