Antiulcer Agent Research Articles

Synthesis, Structure and Gastric H<sup>+</sup>/K<sup>+</sup>-ATPase Inhibitory Activities of Bisabolonalone Hydrazone Carboxamides

Five novel bisabolonalone hydrazone carboxamides were synthesized as potential anti-ulcer agents. Their structures were characterized by NMR, IR and ESI-MS. All of the compounds possessed the better H+/K+-ATPase inhibitory activity than the commercial omeprazole with the IC50 of 18~68 μM in vitro. These compounds could be potentially use for the treatment of ulcer related diseases.

Synthesis and <i>In Vitro</i> Anti-Ulcer Effect of Bisabolangelone Oxime Ether Derivatives

Four bisabolangelone oxime ether derivatives were synthesized and separated as potential anti-ulcer agents. Their structures were characterized by NMR, IR and ESI-MS. Preliminarily H+/K+-ATPase activity evaluation indicated that all the target oxime ethers exhibited the better H+/K+-ATPase inhibitory activities than the commercial omeprazole with the IC50of 17~46 μM. These compounds might be used as potential anti-ulcer agents in the treatment of acid-related diseases.

Synthesis and Structure Elucidation of Novel Oxime Ether Type H/K+-ATPase Inhibitors

Six 6,6-dimethyl-2-phenyl-6,7-dihydrobenzofuran-4(5H)-one oxime derivatives were synthesized, characterized and evaluated as potential anti-ulcer agents. Most of the target compounds exhibited better H+/K+-ATPase inhibitory activity than commercial revaprazan, and both of the two O-propyl oxime ethers displayed the most potent activities with IC50˰̵̱̼͆̓ͅ˰̵̼̓̓˰̸̱̈́̾˰́̀˰μ̝˾ These compounds could be potentially used for the treatment of ulcer disease.

Synthesis and <i>In Vitro</i> Anti-Ulcer Effect of Triazolo-Methyl Tetrahydrobenzofuran Oxime Ether Derivatives

The triazolo-methyl tetrahydrobenzofuran oxime ether isomers were prepared through Cu (II)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction in a high-yielding three-step reaction sequence under mild conditions. All of the intermediates and target compounds were characterized by NMR, IR, ESI-MS and elemental analysis. The in vitro anti-ulcer activity evaluation indicated the (Z)-oxime isomer of triazolo-methyl tetrahydrobenzofuran oxime ether exhibited most potent H+/K+-ATPase inhibitory effect with the IC50˰̵̱̼͆ͅ˰̶̿˰̅˾́̅˰μ̝˾ These compounds could be potentially used as anti-ulcer agents for the treatment of acid related diseases.

English

Non Steroidal anti-inflammatory Drugs (NSAIDs) are most commonly prescribed drugs constituting more than 20% of all drug prescriptions. Prescription pattern study of NSAID was conducted in Medicine OPD of a rural teaching hospital with the objective of analyzing prescribing trend of NSAIDs, to evaluate co-prescription of Gastro-protective agents (GPAs) with NSAIDs and to determine number of prescribed NSAIDs falling within Drug utilization (DU) 90% segment. Overall 200 NSAID prescriptions were analysed. Prevalence of NSAID prescription was 25.71%. Paracetamol (36%) was the commonest drug prescribed. In general non-selective NSAIDs were more commonly prescribed (79.5%) and selective COX-2 inhibitors were least prescribed (1%). High prevalence of nimesulide prescription (19.5%) was a significant finding. Co-prescription of GPAs was high (61%). Four drugs (paracetamol, diclofenac, nimesulide and aceclofenac) fall within DU90% segment. In general prescription pattern requires further rationalization of NSAID usage as more number of drugs constitutes DU90% segment. KEY WORD: Prescription pattern, NSAID, DU90%, GPAs co-prescription. INTRODUCTION: The treatment of pain and inflammation is an important area of therapeutics. Over the past two decades, non steroidal anti-inflammatory drugs (NSAIDs) have played a central role in these indications. NSAIDs constitute the largest single group of drugs used worldwide, constituting more than 20% of all drug prescriptions 1 . In India over 400 formulations of NSAIDs are marketed, resulting in wide spread exposure of patients to this class of drugs and its adverse effects 2 . For all these reasons, studies that evaluate the pattern, extent and frequency of NSAID prescriptions are valuable. The demonstration of two unique isoforms of cyclooxygenase (designated as COX-1 and COX- 2) has led to a greater understanding of the mechanisms of action of NSAIDs and their toxicity 3 . The beneficial anti-inflammatory effect of the NSAIDs had been attributed to inhibition of COX-2, while the gastrointestinal (GI), renal and anti-platelet adverse effects were attributed to COX-1 inhibition 4 . Prescription pattern of NSAID changed frequently over a period of time. With the introduction of the selective COX-2 inhibitors, it has been suggested that they may be more cost-effective because of their improved GI tolerability and a reduction in concomitant prescription of antiulcer agents. This has led to an increase of almost 50% in the total number of NSAID prescriptions dispensed, with COX-2 drugs accounting for two thirds of this increase 3 . Before withdrawal of Rofecoxib, the prescriptions of COX-2 selective inhibitors had accounted for 37% of the total NSAID prescriptions dispensed. After its withdrawal in 2004, following the emergence of evidence of increased cardiovascular morbidity in the APPROVe (Adenomatous Polyp Prevention on Vioxx) study, COX-2 inhibitors represented less than 16% of the

Synthesis, molecular docking and kinetic properties of β-hydroxy-β-phenylpropionyl-hydroxamic acids as Helicobacter pylori urease inhibitors

Inhibition of urease results in Helicobacter pylori growth arrest in the stomach, promoting urease as promising targets for gastrointestinal ulcer therapy. Twenty hybrid derivatives of flavonoid scaffold and hydroxamic acid, β-hydroxy-β-phenylpropionylhydroxamic acids, were therefore synthesized and evaluated against H. pylori urease. Biological evaluation of these compounds showed improved urease inhibition exhibiting micromolar to mid-nanomolar IC50 values. Most importantly, 3-(3-chlorophenyl)-3-hydroxypropionyl-hydroxamic acid (6g) exhibited high potency with IC50 of 0.083 ± 0.004 μM and Ki of 0.014 ± 0.003 μM, indicating that 6g is an excellent candidate to develop novel antiulcer agent. A mixture of competitive and uncompetitive mechanism was putatively proposed to understand the inconsistency between the crystallographic and kinetic studies for the first time, which is supported by our molecular docking studies.

Antimicrobial activity and cytotoxicity of triterpenes isolated from leaves of Maytenus undata (Celastraceae)

BackgroundPlants of the genus Maytenus belong to the family Celastraceae and are widely used in folk medicine as anti-tumour, anti-asthmatic, analgesic, anti-inflammatory, antimicrobial and anti-ulcer agents, and as a treatment for stomach problems. The aim of this study was to isolate and identify active compounds with antifungal activity from Maytenus undata after a preliminary study highlighted promising activity in crude extracts.MethodsSequential extracts of M. undata leaves prepared using hexane, dichloromethane (DCM), acetone and methanol (MeOH) were tested for activity against Cryptococcus neoformans, a fungal organism implicated in opportunistic infections. Bioassay-guided fractionation of the hexane extract using C. neoformans as test organism was carried out to isolate antifungal compounds. The cytotoxicity of compounds isolated in sufficient quantities was evaluated using a tetrazolium-based colorimetric cellular assay (MTT) and a haemagglutination assay (HA).ResultsThe hexane extract was most active with an MIC of 20 μg/ml against C. neoformans. The triterpene compounds friedelin (1), epifriedelanol (2), taraxerol (3), 3-oxo-11α-methoxyolean-12-ene-30-oic acid (4), 3-oxo-11α-hydroxyolean-12-ene-30-oic acid (5) and 3,11-dihydroxyolean-12-ene-30-oic acid (6) were isolated. Compound 6 was isolated for the first time from a plant species. The antimicrobial activity of compounds 1, 3, 5 and 6 was determined against a range of bacteria and fungi implicated in opportunistic and nosocomial infections. Compounds 5 and 6 were the most active against all the tested microorganisms with MIC values ranging between 24 and 63 μg/ml, except against Staphylococcus aureus which was relatively resistant. Compounds 1 and 3 had a low toxicity with an LC50 > 200 μg/ml towards Vero cells in the MTT assay. Compounds 5 and 6 were toxic with LC50 values of 6.03±0.02 and 2.98±0.01 μg/ml, respectively. Compounds 1 and 3 similarly were not toxic to the red blood cells (RBCs) but compounds 5 and 6 were toxic, showing HA titer values of 1.33 and 0.67 respectively.ConclusionsCompounds 5 and 6 were the most active but were also relatively cytotoxic to monkey kidney cells and red blood cells, while the other isolated compounds were less active and less cytotoxic.

Protective effect of ethyl acetate fraction of Acacia ferruginea DC. against ethanol-induced gastric ulcer in rats

Ethnopharmacological relevanceIn traditional systems of medicine, stem bark of Acacia ferruginea DC. is used for the treatment of itching, leucoderma, ulcers, stomatitis and diseases of the blood. In the present study, we determined antioxidant and anti-ulcerogenic activities of Acacia ferruginea stem bark. Materials and methodsAcetone extract and its sub-fractions of Acacia ferruginea stem bark were subjected to assess their antioxidant potential using various in vitro systems such as DPPH•, ABTS•+ scavenging, FRAP and phosphomolybdenum reduction activities. Based on the antioxidant potential, the ethyl acetate fraction was used to evaluate the protective effect of ethanol-induced gastric damage in rat model. Enzyme activities such as superoxide dismutase, glutathione, catalase and lipid peroxidation were also determined in the stomach tissues. ResultsEthyl acetate fraction (AFE) of Acacia ferruginea stem bark registered higher antioxidant and free radical scavenging activities than the crude acetone extract and other fractions. In addition, AFE exhibited that the IC50 values of DPPH (2.5µg/ml) and ABTS (1.8µg/ml) were lower when compared to the standard quercetin (12.4µg/ml and 4.7µg/ml, respectively). In ethanol induced gastric ulcer, administration of AFE at doses of 10mg/kg, 50mg/kg and 100mg/kg body weight prior to ethanol ingestion significantly protected the stomach ulceration. Consequently significant changes were observed in enzyme activities such as SOD, CAT, GSH and LPO in the stomach tissues when compared with ethanol control group. ConclusionIt is concluded that the ethyl acetate fraction of Acacia ferruginea stem bark possessed higher antioxidant and anti-ulcerogenic activities. Based on the results, we suggest that Acacia ferruginea stem bark has potential to provide a therapeutic approach to ethanol mediated ulcer as an effective anti-ulcer agent.

The prevalence and incidence of medicinal cannabis on prescription in The Netherlands

A growing number of countries are providing pharmaceutical grade cannabis to chronically ill patients. However, little published data is known about the extent of medicinal cannabis use and the characteristics of patients using cannabis on doctor's prescription. This study describes a retrospective database study of The Netherlands. Complete dispensing histories were obtained of all patients with at least one medicinal cannabis prescription gathered at pharmacies in The Netherlands in the period 2003-2010. Data revealed prevalence and incidence of use of prescription cannabis as well as characteristics of patients using different cannabis varieties. Five thousand five hundred forty patients were identified. After an initial incidence of about 6/100,000 inhabitants/year in 2003 and 2004, the incidence remained stable at 3/100,000/year in 2005-2010. The prevalence rate ranged from 5 to 8 per 100,000 inhabitants. Virtually all patients used some form of prescription medication in the 6months preceding start of cannabis use, most particularly psycholeptics (45.5%), analgesics (44.3%), anti-ulcer agents (35.9%) and NSAIDs (30.7%). We found no significant association between use of medication of common indications for cannabis (pain, HIV/AIDS, cancer, nausea, glaucoma) and variety of cannabis used. This is the first nationwide study into the extent of prescription of medicinal cannabis. Although the cannabis varieties studied are believed to possess different therapeutic effects based on their different content of tetrahydrocannabinol (THC) and cannabidiol (CBD), no differences in choice of variety was found associated with indication.

Chemical constituents and anti‐ulcerogenic potential of the scales of Cynara scolymus (artichoke) heads

Cynara scolymus L. (Asteraseae) (artichoke) is commonly eaten as a vegetable; its leaves are frequently used in folk medicine in the treatment of hepatitis, hyperlipidaemia, obesity and dyspeptic disorders. The purpose of this study is to determine the chemical composition of the volatile oil and alcoholic extract of artichoke head scales. In addition, the role of the methanol extract as an anti-ulcer agent against ethanol-induced gastric ulcer in rats was evaluated. Six flavonoids and one phenolic acid were obtained from the methanol extract. Also, 37 compounds were identified in the volatile oil, the majority including mono- and sesquiterpenes. The artichoke extracts (200 and 400 mg kg(-1)) significantly (P < 0.05) reduced the ulcer index (55.33% and 72.14% inhibition). Histopathological examination of rat stomachs demonstrated that artichoke induced an increase in gastric mucus production, and a reduction of the depth and severity of mucosal lesions. Artichoke dose-dependently reduced the elevated ethanol gastric malonylaldehyde, and reduced glutathione levels and catalase activity. These results suggest that the head scales of artichoke possess potential anti-ulcer activity. The present paper describes the identification of volatile oil for the first time along with the isolation and identification of the constituents of the methanol extract. Moreover, the high anti-ulcerogenic potential of scales of C. scolymus heads was established here for the first time.

Protective effects of the aqueous extract of &lt;i&gt;Nymphaea lotus&lt;/i&gt; L. (Nymphaeaceae) against ethanol-induced gastric ulcers

Effects of the aqueous extract of Nymphaea lotus were investigated on ethanol induced gastric lesions in rats. The extract (250, 500, 1000 mg/kg) significantly (P 5000 mg/kg. These results shows that aqueous extract of Nymphaea lotus contains active ingredients with a therapeutic potential against gastric ulcers, and thus authenticate the use of Nymphaea lotus as an antiulcer agent in traditional medicine. Keywords : Nymphaeae lotus, ethanol-induced gastric ulcers, gastroprotection,

Análisis de la prescripción de medicamentos en una comunidad geriátrica Argentina

Although polypharmacy may be justified in elderly patients with multiple diseases, it may be dangerous, especially when it includes potentially inappropriate medications (PIM). To identify inappropriate medication and factors associated with the most relevant prescriptions among older people. Cross-sectional observational analysis of drugs prescribed during the first trimester of 2010 to 179 older adults aged 77 ± 8 years (98 women), living in a geriatric reference hospital in Argentina. The use of potentially inappropriate medications (PIM) in elderly patients was analyzed using Beers Criteria updated to 2012. The mean number of drugs prescribed per individual was 6.1 ± 2.7. The most commonly used drugs were anti-ulcer agents (58.1%), agents acting on the renin-angiotensin system (54.2%), antithrombotic medications (50.8%) and benzodiazepines (50.8 %). The use of antacids and anti-ulcer agents, psychotropic drugs and PIM was significantly higher among patients using six or more drugs daily, compared to the less medicated group (odds ratio (OR) = 6.8, 95% confidence intervals (CI) 3.5-13.2; OR=15.0, 95%CI 5.9-38.4; OR=5.0; 95%IC 2.6-9.8, respectively). Thirty one percent of participants using non-steroidal anti-inflammatory drugs, were not receiving medications for gastric protection. One to four drugs included in the Beers list were prescribed to 66% of participants. Despite the high prevalence of use of antacids and anti-ulcer agents, these drugs were not prescribed to a significant proportion of patients using non-steroidal anti-inflammatory drugs. Strategies to optimize pharmacotherapy in the elderly population are urgently required.

Identification of Novel Amino Acid Derived CCK-2R Antagonists As Potential Antiulcer Agent: Homology Modeling, Design, Synthesis, and Pharmacology

The present study revisited the three-dimensional (3D) homology model of CCK-2R using human A(2a) adenosine receptor and the resolved NMR based structure of the third extracellular loop of the CCK-2R as templates. Further in order to identify novel antiulcer agents, rational designing have been performed utilizing the substructure of a well-known CCK-2R antagonist benzotript as a lead molecule and submitted to the combined docking and simulation studies. This led to the understanding of the essential structure requirement as well as variation of binding mode among conformational isomers of small molecule CCK-2R antagonists. In the next step, preparation of each configurational isomer of these molecules was carried out and submitted for their in vitro activity followed by in vivo screening into antiulcer rat model. The biological screening of these compounds has not only validated the developed homology model of CCK-2R but also led to the identification of highly potent CCK-2R antagonist 6a as an orally active and safe candidate molecule having better antiulcer properties than the well-known drug benzotript.

Synthesis and H&lt;sup&gt;+&lt;/sup&gt;/K&lt;sup&gt;+&lt;/sup&gt;-ATPase Inhibitory Activity of 2-Phenyl-6,7-Dihydrobenzofuran-4(5H)-one Oxime Ether Derivatives

Three pairs of 2-phenyl-6,7-dihydrobenzofuran-4(5H)-one oxime and corresponding oxime ether isomers were synthesized and separated as potential anti-ulcer agent. Their structures were characterized by NMR, IR, ESI-MS and elemental analysis. Preliminarily H+/K+-ATPase activity evaluation indicated that all the target compounds had a better inhibitory effect than the commercial omeprazole with the IC50 of 2.0~30.0 μM.

Anti-ulcer activity of NS-EA 51 – A fraction of Nigella sativa seed, in histamine plus pylorus-ligated and hypothermia plus restrain stressed rat models

BackgroundIn spite of all recent advancements, the complete cure of gastric ulcer disease has awaited, to be explored. Earlier we reported the potent anti-secretary and anti-ulcer activities of ethanol extract and a fraction of Nigella sativa, seed (NS) in indomethacin-induced gastric ulcers-models. Therefore, anti-ulcer activity of purified fraction of NS (NS-EA 51) in different experimental gastric ulcer-models was evaluated in the present study. MethodsAnti-ulcer activity of NS-EA 51 was evaluated in histamine plus pylorus ligation (PL) and hypothermia-restrained stress, rats (adult male albino; weighing 180–220 g). Changes in the gastric secretion volume, pH, acid-output, pepsin activity, mucus secretion and ulcer indices were observed in histamine plus PL rats. Effects on gastric mucus secretion and ulcer indices were also evaluated in the hypothermic-restrain stressed models. ResultsNS-EA 51 antagonized histaminic effects on gastric juice volume, pH, acid-output, lesion formation and pepsin activities. Fraction also inhibited gastric ulcer formation induced by hypothermic-restrained stress in this study. But it did not show any significant change in the gastric mucus secretion in above models. The anti-ulcer effects of NS-EA 51 found comparable to the Famotidine, a reference anti-ulcer agent. ConclusionNS-EA 51 fraction isolated from NS may prove an effective anti-ulcer tool.

Synthesis and biological evaluation of novel condensed pyrimidinylmethylsulfinylbenzimidazoles as antiulcer agent

Current therapies to treat gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and other acid-related diseases either prevent stimulation of the parietal cell (H2-receptor antagonists) or inhibit gastric H+/K+-ATPase (proton pump inhibitors). The inhibition of acid production by proton pump inhibitors (PPI’s) provides more effective relief of symptoms and healing. A series of novel 4-substituted-2-(1H-benzimidazol-2-yl)methylsulfinylpyrimidines were synthesized as target compounds and antiulcer activity was done using parameters like total acidity, pH, and total gastric acid volume by pylorus ligation method on Wistar rats. Three different dose levels were employed for testings. The target compounds 4-substituted-2-(1H-benzimidazol-2-yl)methylsulfinylpyrimidines were effective for ulcer treatment and among them compounds 10c, 10d, 8b, and 8c exhibited potent antisecretory activity. Overall, compounds 10c, 10d, 8b, and 8c can be looked upon as potential leads for further development and investigations.

Anti-ulcerogenic activity of the root bark extract of the African laburnum “Cassia sieberiana” and its effect on the anti-oxidant defence system in rats

BackgroundDespite the widespread use of roots of Cassia sieberiana in managing several health conditions including gastric ulcer disease, there is little scientific data to support the rational phytotherapeutics as an anti-ulcer agent. This paper reports an evaluation of the in vivo anti-oxidant properties of an aqueous root bark extract of C. sieberiana in experimental gastric ulcer rats in a bid to elucidate its mechanism of action.MethodsFisher 344 (F344) rats received pretreatment of C. sieberiana root bark extract (500, 750, and 1000 mg/kg body wt.) for 7 days after which there was induction of gastric injury with absolute ethanol. The mean ulcer index (MUI) was calculated and serum total anti-oxidant level determined. Gastric mucosal tissues were prepared and the activity level of the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and myeloperoxidase (MPO) were measured together with the level of lipid hydroperoxides (LPO). Statistical difference between treatment groups was analysed using one-way analysis of variance (ANOVA) followed by Dunnett’s post hoc t test. Statistical significance was calculated at P< 0.05.ResultsThe administration of ethanol triggered severe acute gastric ulcer and pretreatment with C. sieberiana root bark extract significantly and dose dependently protected against this effect. The root bark extract also dose dependently and significantly inhibited the ethanol induced decrease in activity levels of the enzymes SOD, CAT and GPx. The extract also inhibited the ethanol-induced decrease in level of serum total anti-oxidant capacity. The increase in ethanol-induced LPO level and MPO activity were also significantly and dose-dependently inhibited by the root bark extract.ConclusionsThe gastro-cytoprotective effect, inhibition of decrease in activity of gastric anti-oxidant enzymes and MPO as well as the inhibition of gastric LPO level suggests that one of the anti-ulcer mechanisms of C. sieberiana is the anti-oxidant property.

Seasonal Monitoring of Cardiovascular and Antiulcer Agents' Concentrations in Stream Waters Encompassing a Capital City.

Nowadays monitoring pharmaceutical residues from surface waters is a widespread analytical task. Most of the studies are conducted from river waters or sewage treatment plants and mainly in Western Europe or North America. Such studies are seldom published from Eastern Europe, especially from stream waters, even though the prescription and consumption patterns of drugs as well as wastewater treatment procedures are very dissimilar. In Hungary the active substance of the most often prescribed drugs are cardiovascular and antiulcer agents. Hence in our study compounds belonging to these two groups were seasonally monitored in two main streams encompassing the Buda side of the Hungarian capital city and flowing into the Danube. To obtain data on the occurrence, fate, and seasonal variation of the compounds, samples were taken from altogether eleven points located near wastewater treatment plants and confluences. The results gave no identifiable pattern in the seasonal variation of concentrations but the contribution of the tributaries and wastewater treatment plants could be followed as expected. From the runoff corrected estuary concentrations the annual contribution of these streams to pharmaceutical pollution of the Danube could be estimated to be in excess of 1 kilogram for atenolol, famotidine, metoprolol, ranitidine, and sotalol.

Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157

Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, stable in human gastric juice, with no toxicity being reported. Recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and antiplatelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Robert’s cytoprotection and BPC 157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAIDs use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (μg, ng/kg) in parenteral or peroral regimens. Keywords: NSAIDs-gastrointestinal tract lesions, NSAIDs-liver lesions, NSAIDs-brain lesions, aspirin-prolonged bleeding/ thrombocytopenia, stable gastric pentadecapeptide BPC 157, counteraction, antidote against NSAIDs, clinical trials, inflammatory bowel disease, anticoagulants

Toxicity by NSAIDs. Counteraction by Stable Gastric Pentadecapeptide BPC 157

Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, stable in human gastric juice, with no toxicity being reported. Recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and antiplatelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Robert's cytoprotection and BPC 157 beneficial effects on NSAIDs mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAIDs use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAIDs antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAIDs prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (μg, ng/kg) in parenteral or peroral regimens.