Gastroprotective role of a flavonoid-rich subfraction from Fridericia chica (Bonpl.) L. G. Lohmann: a medicinal plant used in the Amazon region.

Fridericia chica is an Amazonian plant used to treat stomach disorders. However, the pharmacological activity of flavonoids in the extract has yet to be investigated. Therefore, we considered that a flavonoid-rich F. chica subfraction (FRS) has gastroprotective functions. For this, before the induction of gastric ulcers with ethanol or piroxicam, the rats received vehicle (water), omeprazole (30 mg/kg), or FRS (30 mg/kg), and the ulcer area was measured macro and microscopically, and the antisecretory action was investigated in pylorus-ligated rats. In addition, the roles of nitric oxide (NO) and nonprotein sulfhydryl compounds (NP-SH) in the gastroprotective effects of FRS were studied. FRS reduced ethanol- and piroxicam-induced ulcerations by 81% and 77%, respectively, as confirmed histologically. Antioxidant effects were observed for FRS through the maintenance of GSH and LPO levels, and the SOD and CAT activity similar to those found in the nonulcerated group. Moreover, FRS avoided the increase in MPO activity and TNF, IL-6, IL-4 and IL-10 levels. Moreover, mucin staining increased in ulcerated rats receiving FRS, and the pharmacological mechanism gastroprotective seems to involve the NO and NP-SH in addition to antisecretory actions. The chemical study by mass spectrometry confirmed the presence of flavonoids in FRS, and molecular docking studies have shown that these compounds interact with cyclooxygenase-1 and NO synthase. Furthermore, there was no indication that FRS had cytotoxic effects. Our results support the popular use of F. chica, and we conclude that the gastroprotection effect promoted by FRS can be attributed to the combined effect of the flavonoids.

Essential Oils: Chemistry and Pharmacological Activities-Part II.

The importance of essential oils and their components in the industrial sector is attributed to their chemical characteristics and their application in the development of products in the areas of cosmetology, food, and pharmaceuticals. However, the pharmacological properties of this class of natural products have been extensively investigated and indicate their applicability for obtaining new drugs. Therefore, this review discusses the use of these oils as starting materials to synthesize more complex molecules and products with greater commercial value and clinic potential. Furthermore, the antiulcer, cardiovascular, and antidiabetic mechanisms of action are discussed. The main mechanistic aspects of the chemopreventive properties of oils against cancer are also presented. The data highlight essential oils and their derivatives as a strategic chemical group in the search for effective therapeutic agents against various diseases.

Gastroprotective effect of Artemisia absinthium L.: A medicinal plant used in the treatment of digestive disorders.

ETHNOPHARMACOLOGICAL RELEVANCE: Wormwood (Artemisia absinthium L.) is traditionally used for stomach pain and gastric relief. However, its possible gastroprotective effect has not yet been experimentally evaluated. AIM OF THE STUDY: This study evaluated the gastroprotective effect of aqueous extracts obtained through hot and room temperature maceration of A. absinthium aerial parts in rats. MATERIALS AND METHODS: The gastroprotective effect of hot aqueous extract (HAE) and room temperature aqueous extract (RTAE) from A. absinthium aerial parts were evaluated in rats using a model of acute gastric ulcer induced by ethanol p.a. The stomachs were collected to measure the gastric lesion area and histological and biochemical analysis. UHPLC-HRMS/MS analysis was used to determine the chemical profile of the extracts. RESULTS: Eight main peaks in the UHPLC chromatogram were identified in both HAE and RTAE extracts: tuberonic acid glycoside (1), rupicolin (2), 2-hydroxyeupatolide (3), yangabin (4), sesartemin (5), artemetin (6), isoalantodiene (7), and dehydroartemorin (8). For RTAE, a higher diversity of sesquiterpene lactones was observed. The groups treated with RTAE at 3%, 10%, and 30% presented a gastroprotective effect, reducing the lesion area by 64.68%, 53.71%, and 90.04%, respectively, when compared with the vehicle (VEH)-treated group. On the other hand, the groups treated with HAE at 3%, 10%, and 30% presented values of lesion areas higher than those of the VEH group. Changes in the submucosa layer, inflammatory process with edema, cellular infiltration, and mucin depletion were detected in the gastric mucosa exposed to ethanol, which was fully prevented by RTAE treatment. Neither HAE nor RTAE could increase the reduced glutathione levels in the injured gastric tissue, but RTAE (30%) reduced the formation of lipid hydroperoxides. When the rats were pre-treated with NEM (a chelator of non-protein thiols) or L-NAME (non-selective nitric oxide synthase inhibitor), the RTAE lost the ability to protect the gastric mucosa. CONCLUSIONS: This study corroborates the ethnopharmacological use of this specie to treat gastric disorders revealing the gastroprotective effect of the room-temperature aqueous extract of A. absinthium aerial parts. Its mode of action may involve the ability of the infusion to maintain the gastric mucosal barrier integrity.

Application of Heterocycles as an Alternative for the Discovery of New Anti-ulcer Compounds: A Mini-Review.

A peptic ulcer is a lesion located in the esophagus, stomach, and upper intestine, caused by an imbalance between acid secretion and the release of protective mucus. This pathology is prevalent in approximately 14% of the world population and is commonly treated with proton pump inhibitors and type 2 histaminergic receptor antagonists, however, these drugs present concerning side effects that may lead to gastric cancer. In this sense, this research aimed to present the main heterocyclics studied in recent years. The screening method for the choice of articles was based on the selection of publications between 2000 and 2021 present in the Science Direct, Web of Science, Capes, and Scielo databases, by using the descriptors ''new derivatives'', "heterocyclics" "antiulcerogenic", "gastroprotective" and "antisecretor". This research showed that the most used rings in the development of anti-ulcer drugs were benzimidazole, quinazoline, thiazole, and thiadiazole. The results also portray several types of modern in silico, in vitro and in vivo assays, as well as the investigation of different mechanisms of action, with emphasis on proton pump inhibition, type 2 histaminergic receptor blockers, potassium competitive acid blockers, type E prostaglandin agonism, anti-secretory activity and anti-oxidant action. Additionally, the review evidenced the presence of the nitrogen atom in the heterocyclic ring as a determinant of the potential of the compound. This research suggests new alternatives for the treatment of gastric lesions, which may be more potent and cause fewer side effects than the currently used, and tend to evolve into more advanced studies in the coming years.

Análise da utilização de inibidores de bomba de prótons em pacientes internados em um hospital universitário do interior de São Paulo / Analysis of the use of proton pump inhibitors in patients admitted to a university hospital in interior of São Paulo

Introdução: A crença de que o uso de Inibidores de Bomba de Prótons (IBPs) apresenta baixo risco de toxicidade, resultou em um aumento significativo na sua prescrição em nível mundial, esse fator juntamente com a baixa divulgação de orientações, têm contribuído para o aumento das indicações desnecessárias de inibidores de bomba de prótons em nível hospitalar, principalmente para profilaxia. Objetivo: Analisar a utilização dos inibidores de bomba de prótons em pacientes internados nas enfermarias de clínica médica de um Hospital Universitário, visando avaliar suas indicações, tempo de uso, efeitos adversos e impacto financeiro gerado pelo uso inadequado. Métodos: Foram analisados prontuários de pacientes que estiveram internados nas enfermarias de clínica médica do Hospital Municipal Universitário de Taubaté (HMUT) durante os meses de maio a julho de 2020. As indicações adequadas do uso de inibidores de bomba de prótons foram baseadas em diretrizes internacionais do American Journal of Gastroenterology e do American Society of Health-System Pharmacy. Resultados: Identificamos que 297 pacientes (79,6%) usaram inibidores de bomba de prótons em algum momento da internação. O uso desse medicamento foi adequadamente prescrito em 49,8% dos casos. Foi encontrado maior prevalência de pneumonia e diarreia nos pacientes que fizeram uso de inibidores de bomba de prótons a longo prazo. O custo anual associado as prescrições indevidas foram de R$24.736,40. Conclusão: Observamos alta prevalência de indicações incorretas dos inibidores de bomba de prótons em ambiente hospitalar, ocasionando gasto desnecessário e possíveis complicações. Faz-se necessário, portanto, elaboração de novos protocolos e maior rigidez nas indicações desses medicamentos no Hospital Municipal Universitário de Taubaté.

Introduction: The belief that the use of Proton Pump Inhibitors (PPIs) presents a low risk of toxicity, resulted in a significant increase in its prescription worldwide, this factor combined with the low disclosure of guidelines, have contributed to the increase in unnecessary indications of at the hospital level, especially for prophylaxis. Objective: To analyze the use of proton pump inhibitors in patients hospitalized in the medical clinic wards of a University Hospital, in order to evaluate their indications, time of use, adverse effects and financial impact generated by inadequate use. Methods: Medical records of patients who were admitted at the Municipal University Hospital of Taubaté during the months of May to July 2020 were analyzed. The appropriate indications for the use of proton pump inhibitors were based on the international guidelines of the American Journal of Gastroenterology and the American Society of Health-System Pharmacy. Results: We identified that 297 patients (79.6%) used proton pump inhibitors at some point in hospitalization. The use of this drug was adequately prescribed in 49.8% of the cases. A higher prevalence of pneumonia and diarrhea was found in patients who used proton pump inhibitors in the long term. The annual cost associated with undue prescriptions was R$24,736.40. Conclusion: We observed a high prevalence of incorrect indications of proton pump inhibitors s in the hospital environment, causing unnecessary expenses and possible complications. It is necessary, therefore, the elaboration of new protocols and greater rigidity in the indications of these drugs at the Municipal University Hospital of Taubaté.

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology.

Mulinane- and azorellane-type diterpenoids have unique tricyclic fused five-, six-, and seven-membered systems and a wide range of biological properties, including antimicrobial, antiprotozoal, spermicidal, gastroprotective, and anti-inflammatory, among others. These secondary metabolites are exclusive constituents of medicinal plants belonging to the Azorella, Laretia, and Mulinum genera. In the last 30 years, more than 95 mulinanes and azorellanes have been reported, 49 of them being natural products, 4 synthetics, and the rest semisynthetic and biotransformed derivatives. This systematic review highlights the biosynthetic origin, the chemistry, and the pharmacological activities of this remarkably interesting group of diterpenoids.

Chemical profile and gastroprotective effect of Jatropha elliptica (Pohl) Oken roots.

Jatropha elliptica (Pohl) Oken (Euphorbiaceae) roots are used in folk medicine to treat gastric ulcers. The purpose of this work was to evaluate the gastroprotective activity of ethanol extract (JER) and hexane fraction (ERH) of J. elliptica roots in mice, as well as to analyze the acute toxicity of the extract and identify the potential active compounds. No signs of toxicity were observed in JER. In both acidified ethanol and indometacin-induced gastric ulcer models, all doses tested of JER and ERH significantly reduced gastric lesions. Dereplication of JER was performed by HPLC-DAD-ESI-MS/MS and resulted in the annotation of compounds fraxetin, propacin, jatrophone and jatropholones A and B. GC-MS analysis of ERH revealed the diterpenes jatrophone, jatropholone A and jatropholone B as the major components. The chemical study of this fraction has led to the isolation of these compounds, in addition to the sequiterpene cyperenoic acid and the diterpene 2ß-hydroxyjatrophone, both reported for the first time in J. elliptica. The isolated compounds were tested against L929 cells and only cyperenoic acid and the mixture of jatropholones A and B did not show toxicity, being then selected as good candidates for bioassays using acidified ethanol-induced gastric ulcer model. Cyperenoic acid significantly decreased gastric lesions and preserved gastric mucus layer. The mixture of jatropholones A and B caused a smaller reduction of gastric lesions, without preservation of the gastric mucus layer. The study showed that J. elliptica roots present gastroprotective activity in mice, without causing acute toxic effects. The activity is related, at least in part, to the occurrence of terpenes, mainly the sesquiterpene cyperenoic acid.

Adesão a um protocolo de profilaxia de úlcera de estresse em pacientes críticos: estudo de coorte prospectiva / Adherence to a stress ulcer prophylaxis protocol by critically ill patients: a prospective cohort study

RESUMO Objetivo: Avaliar a adesão ao protocolo de profilaxia de úlcera de estresse em pacientes críticos de um hospital universitário terciário. Métodos: Neste estudo de coorte prospectiva, incluímos todos os pacientes adultos admitidos às unidades de terapia intensiva clínica e cirúrgica de um hospital terciário acadêmico. Nosso único critério de exclusão foi a presença de sangramento gastrointestinal alto quando da admissão à unidade de terapia intensiva. Colhemos as variáveis basais e indicações de profilaxia de úlcera de estresse, segundo o protocolo institucional, assim como o uso de profilaxia. Nosso desfecho primário foi a adesão ao protocolo de profilaxia de úlcera de estresse. Os desfechos secundários foram uso apropriado da profilaxia de úlcera de estresse, incidência de sangramento gastrointestinal superior e fatores associados com o uso apropriado da profilaxia de úlcera de estresse. Resultados: Foram incluídos 234 pacientes no período compreendido entre 2 de julho e 31 de julho de 2018. Os pacientes tinham idade de 52 ± 20 anos, sendo 125 (53%) deles cirúrgicos, e o SAPS 3 médio foi de 52 ± 20. No seguimento longitudinal, foram estudados 1.499 pacientes-dias; 1.069 pacientes-dias tiveram indicação de profilaxia de úlcera de estresse, e 777 pacientes-dias tiveram uso profilático (73% de adesão ao protocolo de profilaxia de úlcera de estresse). Dentre os 430 pacientes-dias sem indicações de profilaxia de úlcera de estresse, 242 envolveram profilaxia (56% de uso impróprio de profilaxia de úlcera de estresse). O total de uso apropriado de profilaxia de úlcera de estresse foi de 64%. Fatores associados com prescrição adequada de profilaxia de úlcera de estresse foram ventilação mecânica, com RC 2,13 (IC95% 1,64 - 2,75), e coagulopatia, com RC 2,77 (IC95% 1,66 - 4,60). A incidência de sangramento do trato gastrointestinal superior foi de 12,8%. Conclusão: A adesão ao protocolo de profilaxia de úlcera de estresse foi baixa, e o uso inadequado de profilaxia de úlcera de estresse foi frequente nesta coorte de pacientes críticos.

ABSTRACT Objective: To evaluate adherence to the stress ulcer prophylaxis protocol in critically ill patients at a tertiary university hospital. Methods: In this prospective cohort study, we included all adult patients admitted to the medical and surgical intensive care units of an academic tertiary hospital. Our sole exclusion criterion was upper gastrointestinal bleeding at intensive care unit admission. We collected baseline variables and stress ulcer prophylaxis indications according to the institutional protocol and use of prophylaxis. Our primary outcome was adherence to the stress ulcer prophylaxis protocol. Secondary outcomes were appropriate use of stress ulcer prophylaxis, upper gastrointestinal bleeding incidence and factors associated with appropriate use of stress ulcer prophylaxis. Results: Two hundred thirty-four patients were enrolled from July 2nd through July 31st, 2018. Patients were 52 ± 20 years old, 125 (53%) were surgical patients, and the mean SAPS 3 was 52 ± 20. In the longitudinal follow-up, 1499 patient-days were studied; 1069 patient-days had stress ulcer prophylaxis indications, and 777 patient-days contained prophylaxis use (73% stress ulcer prophylaxis protocol adherence). Of the 430 patient-days without stress ulcer prophylaxis indications, 242 involved prophylaxis (56% inappropriate stress ulcer prophylaxis use). The overall appropriate use of stress ulcer prophylaxis was 64%. Factors associated with proper stress ulcer prophylaxis prescription were mechanical ventilation OR 2.13 (95%CI 1.64 - 2.75) and coagulopathy OR 2.77 (95%CI 1.66 - 4.60). The upper gastrointestinal bleeding incidence was 12.8%. Conclusion: Adherence to the stress ulcer prophylaxis protocol was low and inappropriate use of stress ulcer prophylaxis was frequent in this cohort of critically ill patients.

Systematic Analysis of Monoterpenes: Advances and Challenges in the Treatment of Peptic Ulcer Diseases.

Peptic ulcer disease (PUD) is a multifactorial and complex disease caused by an imbalance of protective and aggressive factors (endogenous and exogenous). Despite advances in recent years, it is still responsible for substantial mortality and triggering clinical problems. Over the last decades, the understanding of PUD has changed a lot with the discovery of Helicobacter pylori infection. However, this disease continues to be a challenge due to side-effects, incidence of relapse from use of various anti-ulcer medicines, and the rapid appearance of antimicrobial resistance with current H. pylori therapies. Consequently, there is the need to identify more effective and safe anti-ulcer agents. The search for new therapies with natural products is a viable alternative and has been encouraged. The literature reports the importance of monoterpenes based on the extensive pharmacological action of this class, including wound healing and anti-ulcerogenic agents. In the present study, 20 monoterpenes with anti-ulcerogenic properties were evaluated by assessing recent in vitro and in vivo studies. Here, we review the anti-ulcer effects of monoterpenes against ulcerogenic factors such as ethanol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori, highlighting challenges in the field.

Perfil sociodemográfico e clínico de idosos usuários crônicos de omeprazol na rede básica de saúde / Sociodemographic and clinical profile of elderly people chronic users of omeprazole attending the basic health network / Perfil sociodemográfico y clínico de los ancianos usuarios crônicos de omeprazol em la red básica de salud

Objetivo: Descrever o perfil sociodemográfico e clínico de idosos usuários crônicos de omeprazol. Método: Trata-se de um estudo transversal com usuários com idade superior a 60 anos, que retiraram o omeprazol na Farmácia Pública de Panambi/RS. Resultados: Participaram da pesquisa sessenta idosos, com idade média de 67,90 ±5,6 anos. Duas interações graves foram identificadas envolvendo citalopram e clopidogrel. Observou-se a presença nas prescrições de medicamentos que tem a sua absorção alterada pelo uso concomitante com o omeprazol como captopril (25%) e enalapril (16,7%). Conclusão: Dessa forma, evidenciou-se uma população suscetível a riscos que necessita de acompanhamento farmacêutico

Objective: To describe the sociodemographic and clinical profile of elderly chronic omeprazole users. Method: This is a cross-sectional study. Patients aged 60, from the Public Pharmacy of the city of Panambi / RS. Results: A total of 60 elderly chronic omeprazole users participated in the study with an average of 67.90 ± 5.6 years of age. Two serious interactions were identified involving citalopram and clopidogrel. There was the presence in the prescription of drugs that have their absorption altered by concomitant use of omeprazole as captopril (25%) and enalapril (16.7%). Conclusion: Thus, we highlight that there is a population susceptible to risks that needs pharmaceutical monitoring

Objetivo: Describir el perfil sociodemográfico y clínico de los ancianos usuarios crónicos de omeprazol. Método: Es un estudio transversal descriptivo cuantitativo. Participaron en el estudio pacientes con edad igual o mayor de 60 años, usuarios crónicos de omeprazol, y que acudieron al medicamento en la Farmacia Publica de la cuidad de Panambi/RS. Resultados: Participaron de la investigación 60 ancianos 51,7% del sexo femenino, con edad media de 67,90 ±5,6 años, 81,7% relataran alguna comorbilidad, siendo la más prevalente la hipertensión arterial sistémica (61,7%). Los medicamentos que actúan en el tracto alimentar y metabólico fueron los más frecuentes. Se identificaron dos graves interacciones relacionado al citalopram (8,4%) y clopidogrel (1,7%). Se observó en las prescripciones la presencia de medicamentos cuya absorción es alterada por el uso concomitante con el omeprazol, como el captopril (25%) y enalapril (16,7%). Conclusión: De esta forma, se ha evidenciado una populación susceptible a los riesgos y que necesita de acompañamiento farmacéutico

Avocado seeds (Persea americana Mill.) prevents indomethacin-induced gastric ulcer in mice.

The long-term use of anti-inflammatory drugs is the most common cause of gastric ulcer disease, one of the major gastrointestinal disorders affecting people worldwide. Persea americana Mill. (avocado) seed is a by-product generally discarded as waste, but can be used to treat gastric disorder due to its anti-inflammatory, antioxidant and antimicrobial activities. The aim of the present study was to evaluate the potential protective effects of the ethyl acetate fraction of avocado seeds (SEAP) extracts against indomethacin-induced gastric ulcer in mice. It was found that SEAP were effective in mitigating oxidative stress through a decrease on the oxidized products levels (reduction of 90% in lipid peroxidation in plasma) and increasing superoxide dismutase enzyme (SOD) activity (4.25-fold increase compared to the indomethacin group), also preventing the rise in ulcer and lesions areas (92% of protection) and histological changes induced by indomethacin. Chemical analysis using mass spectrometry by (-)-ESI-FT-ICR MS revealed the presence of (-)-epicatechin and (+)-catechin, confirmed by HPLC-DAD, and other important phenolic compounds in avocado seeds, such as caffeoylquinic acid, flavonoids, phenylpropanoids and tannins, substances that promote inhibition of pathways involved in gastric ulcer formation. Thus, avocado seeds extract may be a suitable natural source for the prevention and treatment of gastric ulcer.

Chemistry and Biology of Selected Mexican Medicinal Plants.

Herbal medicines are an integral element of alternative medical care in Mexico, and the best testimony to their efficacy and cultural value is their persistence in contemporary Mexican marketplaces where the highest percentages of medicinal and aromatic plants are sold. This chapter summarizes current trends in research on medicinal plants in Mexico, with emphasis on work carried out at the authors' laboratories. The most relevant phytochemical and pharmacological profiles of a selected group of plants used widely for treating major national health problems are described.From this contribution, it is evident that in the last five decades a significant amount of research on medicinal plants has been performed by Mexican scientists. Such efforts have led to the publication of many research papers in noted peer-reviewed journals and technical books. The isolation and structural characterization of hundreds of bioactive secondary metabolites have been accomplished, and most importantly, these studies have tended to support the ethnomedical uses of many different species. A multidisciplinary approach for investigating these plants has led to an increased emphasis on areas such as phytopharmacology, phytotoxicology, quality control, regulation, and conservation issues for these valuable resources. The medicinal plants analyzed so far have shown a very broad chemical diversity of their constituents, which have a high potential for exhibiting novel mechanistic effects biologically. The chapter shows also that there is need to conduct additional clinical studies on herbal drugs, in particular because the longstanding traditional evidence for their safety is not always sufficient to assure their rational use. There is also need to move to "omics" approaches for investigating the holistic effect and the influence of groups of phytochemicals on the whole organism. Mexican scientists may be expected to have bright prospects in this regard, which will imbue medicinal plant research with a new dynamism in the future.

Cochlospermum regium (Mart. ex Schrank) Pilg.: Evaluation of chemical profile, gastroprotective activity and mechanism of action of hydroethanolic extract of its xylopodium in acute and chronic experimental models.

ETHNOPHARMACOLOGICAL RELEVANCE: Cochlospermum regium (Bixaceae) is a native shrub of Brazil and its xylopodium (infusion/decoction) is being used for the treatment of gastritis, ulcers, arthritis, intestinal infections, gynaecological infections, skin diseases, among others. The aim of the present study was to evaluate the gastroprotective/antiulcer activity and the mechanism of action of hydroethanolic extract of C. regium xylopodium (HECr), using in vitro and in vivo models. Additionally, phytochemical constituents were identified by high-performance liquid chromatography (HPLC). MATERIALS AND METHODS: C. regium xylopodium was macerated with ethanol/water to obtain the HECr. The phytochemical characterisation was carried out by HPLC. The antiulcer efficacy of HECr (25, 100 and 400 mg/kg, p.o.) was evaluated using acute acidified ethanol (HCl/EtOH), piroxicam and water immersion-induced experimental ulcer models. Chronic gastric ulcer healing activity of HECr was evaluated through acetic acid (99.8%) - induced model. Histological analysis and myeloperoxidase (MPO), glutathione (GSH), catalase (CAT) activities were also evaluated in chronic ulcer induced gastric tissues. The plausible mode of action of the HECr was assessed by estimation of gastric wall mucus production and the role of gastric secretion in pylorus ligature. The animals were also pre-treated with various inhibitors which includes indomethacin (10 mg/kg, p.o.) a selective inhibitor of cyclooxygenase, L-NAME (10 mg/kg, i.p.), an inhibitor of nitric oxide synthase, glibenclamide, a ATP-sensitive potassium channels (K+ATP) blocker (5 mg/kg, p.o.) or yohimbine (2 mg/kg, i.p.), an α2-adrenergic receptor antagonist. In vitro, Helicobacter pylori action was done by broth microdilution method. RESULTS: The HPLC analysis data revealed the presence of gallic acid, rutin, myricetin, morin and kaempferol. HECr promoted protective effect against acute ulcers induced by HCl/EtOH with inhibitions of 47.52% (p < 0.01) and 62.69% (p < 0.001) at 100 and 400 mg/kg, and in piroxicam by 34.11% (p < 0.05), 49.14% (p < 0.01) and 61.34% (p < 0.001), at 25, 100 or 400 mg/kg, respectively, and in water restraint stress by 78.26% inhibition, p < 0.001, at the dose of 400 mg/kg when compared to the vehicle control group respectively. In the chronic gastric ulcer model, HECr (25, 100 and 400 mg/kg p.o.) significantly (p < 0.001) decreased the injured area by 58.80%, 77.87% and 71.10% respectively. Histological examination indicated that oral treatment of HECr promoted healing of gastric lesions by regenerating gastric mucosa layer with less inflammatory cells. HECr augmented the GSH, CAT activities and reduced MPO level. The pre-treatment with HECr increased the gastric wall mucus production. It also significantly altered the gastric secretion parameters by causing the reduction in the gastric juice volume, elevated the pH level and reduced the total acidity at all doses tested when compared with the vehicle group. HECr at the most active dose (100 mg/kg) reversed completely the reduction of PGs, NO production, closure of K+ATP- channels and α2-adrenoreceptor blockage - induced damages. In microdilution assay, the HECr showed good anti-Helicobacter pylori effect with MIC = 100 µg/mL. CONCLUSION: The HECr presented preventive and curative effects in the experimental gastric ulcer models, besides good anti-Helicobacter pylori activity, which supports the traditional medicinal use of the xylopodium of this plant for gastrointestinal diseases. The underlying mechanisms of this antiulcerogenic/antiulcer action involve, at least, augmentation of mucus production, inhibition of gastric secretion, stimulation of PGs and NO synthesis. And that it involves activation of K+ATP channels and α-2-adrenergic receptors, in addition to an antioxidant activity, probably due to the presence of gallic acid and flavonoids in HECr.

Chemical characterization and evaluation of gastric antiulcer properties of the hydroethanolic extract of the stem bark of Virola elongata (Benth.) Warb.

ETHNOPHARMACOLOGICAL RELEVANCE: Virola elongata is a tree species belonging to the Myristicaceae family, distributed in the North and Midwest regions of Brazil, in the phytogeographic domain of the Amazon. The aqueous infusion or the hydroethanolic macerate of the stem bark of V. elongata are used in Brazilian and Ecuadorian indigenous folk medicine for several ethnopharmacological purposes, principally, in the treatment of stomach pain, indigestions, and gastric ulcers. This study was aimed to investigate the gastroprotective activity of this plant in order to support its popular use with scientific evidence. MATERIALS AND METHODS: The stem bark hydroethanolic extract of the plant (HEVe) was prepared by maceration. Its qualitative and quantitative phytochemical constituents were investigated by classical colorimetric techniques, HPLC, and electrospray ionization-multiple stage fragmentation (ESI-MSn). The gastroprotective and antiulcer activity of HEVe at doses of 100, 300 and 900 mg/kg p.o. were tested using three acute (acidified ethanol, piroxicam, and in-water-restrain stress), and one chronic (acetic acid) animal ulcer models. The probable mode of action of the HEVe was evaluated by analyzing gastric acid secretion, mucus content, nitric oxide effect, and its antioxidant properties (on catalase, myeloperoxidase, and GSH content) in experimental rodents. The direct extract's activity on the growth of Helicobacter pylori was also investigated. RESULTS: Total phenolic content in the HEVe was of 146.20 ±â€¯1.07 mg, being flavonoids about 50% (71.79 ±â€¯0.70 mg) of it. Comparative HPLC fingerprint analysis revealed the presence of known phenolic antiulcer compounds, such as gallic acid, catechin, and rutin. Also, methanol/water fractionation and ESI-MSn analysis of the HEVe reveals the presence of quinic acid, 3,3',4-trihydroxystilbene, juruenolid D, one catechin dimer, one C-glycosyl flavonoid, one polyketide and two neolignans as the major components of the extract. The HEVe attenuated gastric ulceration in all the different models of acute gastric ulcer, by enhancing gastroprotection through its antioxidant properties in vivo, and reducing also considerably the gastric secretion and total acidity. The HEVe also presented healing properties against the induced chronic ulceration process. On the other hand, the HEVe did not exhibit direct activity against H. pylori. CONCLUSION: The HEVe exhibited significant gastroprotective/antiulcer effects and contain a relative high proportion of phenolic compounds, especially flavonoids, that could likely account, at least in part, for its pharmacological properties. The results justify its traditional usage and provided scientific evidence for its potential as a new herbal medicine to treat gastric ulcers.

Chemical composition, antioxidant and gastrointestinal properties of Sedum dendroideum Moc & Sessé ex DC leaves tea infusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is a medicinal plant employed in Mexican and Brasilian folk medicine as juice or infusion, as remedy for the treatment of different diseases, including gastric disorders. AIM OF THE STUDY: Although some studies carried out with Sedum dendroideum have demonstrated its gastroprotective effect, the purpose of this study was to elucidate the chemical constituents, antioxidant, cytotoxic and mechanisms underlying the gastrointestinal properties of Sedum dendroideum accordingly its traditional use, as fresh leaves tea infusion (SDI). MATERIALS AND METHODS: Chemical constituents were analyzed using high performance liquid chromatography and mass spectrometry (HPLC-MS). Antioxidant and cytotoxicity were evaluated in in vitro assays. The efficacy of the SDI on macroscopic ulcer appearance, mucus and GSH maintenance on ethanol- and indomethacin-induced ulcer models, gastric acid secretion and gastrointestinal motility were investigated. RESULTS: Phytochemical analysis by HPLC-MS revealed the presence of different flavonol glycosides, containing myricetin and quercetin, along with the kaempferol as aglycones. In vitro pharmacological investigation of SDI demonstrated potent antioxidant activity in DPPH assay (IC50: 13.25 ±â€¯3.37 µg/mL) and absence of cytotoxicity in Caco-2 cells by MTT method. Oral administration of SDI (ED50 of 191.00 ±â€¯0.08 mg/kg) in rats promoted gastroprotection against ethanol or indomethacin in rats through reinforcement of gastric wall mucus, GSH content and nitric oxide release, without present antisecretory properties. The gastroprotective effect was maintained when SDI (19 mg/kg) was administrated by intraperitoneal route. Furthermore, SDI (150 mg/kg) unchanged the gastric emptying but increase small bowel transit in mice through cholinergic pathways. CONCLUSIONS: Collectively, this study confirmed that Sedum dendroideum promotes gastroprotection through preventing of endogenous defense mechanisms, represented by mucus and GSH without changes gastric acid secretion. Sedum dendroideum tea infusion features a chemical profile that contributes to the antioxidant and gastric health-promoting effects, supporting the use in folk medicine for the treatment of gastrointestinal disorders.

Perfil fitoquímico e atividade gastroprotetora dos frutos de Eugenia mattosii / Phytochemical profile and gastroprotective activity of eugenia mattosii fruits

ABSTRACT BACKGROUND: Extracts obtained from plants and fruits provide a relatively safe and practical alternative for the conventional medicine of gastrointestinal diseases. The specie Eugenia mattosii, popularly known in Brazil as "cerejinha", belongs to Myrtaceae family. Species of this family present pharmacological properties, and can be used in the treatment of gastrointestinal disorders. OBJECTIVE: The aim of this study was to determine the phytochemical profile and evaluate the gastroprotective activity of Eugenia mattosii fruits. METHODS: Phytochemical analysis was carried out by thin layer chromatography and gastroprotective assays were performed using two experimental models: acute ulcer model induced by ethanol/HCl and acute ulcer model induced by non-steroidal anti-inflammatory drug (indomethacin). Total lesion area (mm2) and relative lesion area (%) were determined. RESULTS: The results of the phytochemical analysis indicated that the bark and pulp and seeds of E. mattosii present phenolic compounds, terpenes and/or steroids. In gastric ulcer model induced by ethanol was evidenced significant reduction of damaged areas for doses of 50 and 250 mg/ kg of seeds methanol extract, while in the indomethacin-induced ulcer model, all parts of the fruit presented defense capability of the gastric mucosa by reducing lesions at doses of 50, 125 and 250 mg/kg. CONCLUSION: The results demonstrate that the specie E. mattosii has bioactive compounds that provide gastroprotective activity, presenting possible therapeutic potential.

RESUMO CONTEXTO: Extratos obtidos de plantas e frutos fornecem uma alternativa relativamente segura e prática para os remédios convencionais de doenças gastrointestinais. A espécie Eugenia mattosii, popularmente conhecida no Brasil como "cerejinha", pertence à família Myrtaceae. Espécies desta família apresentam propriedades farmacológicas e podem ser utilizadas no tratamento de distúrbios gastrointestinais. OBJETIVO: O objetivo deste estudo foi determinar o perfil fitoquímico e avaliar a atividade gastroprotetora dos frutos de Eugenia mattosii. MÉTODOS: A análise fitoquímica foi realizada por cromatografia em camada delgada e dois modelos experimentais foram utilizados para avaliação da atividade gastroprotetora em camundongos: modelo de úlcera gástrica induzida por anti-inflamatório não-esteroidal (indometacina) e modelo de úlcera gástrica induzida por etanol/HCl. RESULTADOS: Os resultados da análise fitoquímica indicaram que a casca e polpa e as sementes de E. mattosii apresentam compostos fenólicos, terpenos e/ou esteroides. No modelo de úlcera gástrica induzido pelo etanol, foi evidenciada redução significativa de áreas danificadas para doses de 50 e 250 mg/kg do extrato das sementes, enquanto no modelo de úlcera induzida por indometacina, todas as partes do fruto apresentaram capacidade de defesa da mucosa gástrica ao reduzir as lesões nas doses de 50, 125 e 250 mg/kg. CONCLUSÃO: Os resultados demonstram que a espécie E. mattosii possui compostos bioativos com atividade gastroprotetora, apresentando possível potencial terapêutico.

Pharmacological mechanisms underlying gastroprotective activities of binapthyl diselenide in Wistar rats.

Selenium (Se) is a dietary essential trace element with important biological roles. It is a nutrient related to the complex metabolic and enzymatic functions. Organoselenium compounds have been reported to have anti-ulcer activity and used as drug for the treatment of gastrointestinal disorders. The antiulcer activity of binapthyl diselenide (NapSe)2 was investigated in ethanol-induced gastric lesions in rats. A number of markers of oxidative stress were examined in rats stomach including thiobarbituric acid reactive species (TBARS), catalase (CAT), superoxide dismutase (SOD), non-protein thiol groups (NPSH) and ascorbic acid. (NapSe)2 was found to be significantly restoring the deficits in the antioxidant defense mechanisms (CAT, SOD, NPSH and ascorbic acid), and suppressed lipid peroxidation in rat stomach resulting from EtOH administration. It is experimentally concluded that ethanol exposure causes alterations in the antioxidant defense system and induces oxidative stress in rat stomach. These studies establish a promising foundation for investigating and understanding the beneficial effects of organoselenium compounds on human health. Moreover, (NaPSe)2 deserves further investigation as a therapeutic and preventive agent against gastric ulcer in humans.

Gastroprotective activity of the methanol extract from peels of Plinia edulis (Vell.) Sobral fruits and its isolated triterpenes: maslinic and ursolic acids.

According to the Brazilian folk medicine, the leaves of Plinia edulis (Vell.) Sobral (Myrtaceae), known as cambuca, are indicated in the treatment of gastric disorders. Infusions of P. edulis leaves were previously demonstrated to contain both maslinic (MA) and ursolic acids (UA). Both triterpenes have also been identified in the methanolic extract of peels from P. edulis fruit (MEPPE); however, the antiulcer effects of MEPPE have not yet been studied. This study therefore evaluates the gastroprotective potential of MEPPE, MA, and UA using ethanol/HCl- and indomethacin-induced gastric ulcers in mice. In addition, the in vitro effects of these compounds on the H+, K+-ATPase activity and on the free radical DPPH were measured. When used at concentration of 100 µg/mL, both MEPPE and UA were found to reduce the DPPH radical levels by 78.66 and 60.14%, respectively. However, MA did not reduce DPPH radical levels. Our results illustrated the antiulcer effects of MEPPE, MA, and UA against experimental ulcer models when administered by either the oral or the intraperitoneal routes. In addition, MEPPE reduced the size of ethanol/HCl-induced ulcers in a dose-dependent manner (log half-maximal effective oral dose, LogED50 = 1.09). Interestingly, UA promoted gastroprotection at lower doses than MA by increasing the production of mucin levels at 692%; however, it does not alter the activity of H+, K+-ATPase. In contrast, both MEPPE and MA, when incubated at concentrations of 10 and 100 µg/mL, inhibited H+, K+-ATPase activity in 61.81, 68.37, 54.04, and 70.45%, respectively. These results confirm that MEPPE, MA, and UA display gastroprotective activity through different modes of action; MA inhibits H+, K+-ATPase activity, whereas UA favour the mucus barrier.

Himatanthus drasticus: a chemical and pharmacological review of this medicinal species, commonly found in the Brazilian Northeastern region

ABSTRACT In order to compile the empirical use, as well as the chemical, pharmacological and biological aspects of Himatanthus drasticus (Mart.) Plumel, Apocynaceae, a review was carried out by searching PubMed, Google Scholar, Scientific Electronic Online Library, Web of Science, Science Direct, Scopus and Cochrane. For that, works in English, Spanish and Portuguese, preclinical studies and revisions, addressing chemical, pharmacological, biological properties and popular uses, from 1994 to 2017, were used. The therapeutic potential of the "milk-of-janaguba" (a mixture of the latex with water) became widely known for the treatment of neoplasias, mainly lung and lymphatic cancer types, in the 1970s. The available literature presents works related to the anti-inflammatory, antinociceptive, antitumor and gastroprotective properties of the latex from bark and leaves of H. drasticus. In addition, this review presents some of our own results with the triterpene-rich fraction from H. drasticus, attempting to clarify its action mechanisms at the molecular level. The antinociceptive and anti-inflammatory activities of H. drasticus are probably associated with inhibitions of inflammatory mediators, as TNF-alpha, iNOS, COX-2 and NF-kB. Most importantly, a triterpene-rich fraction also inhibited HDAC activity, and compounds with this activity have been considered as therapeutic agents with antitumor activity. In conclusion, although the literature shows several works on species of the Himatanthus genus, including H. drasticus, dealing with some bioactive compounds as triterpenes, translational studies focusing upon the clinical uses of this medicinal species are still in great need.

Pharmacological and Toxicological Study of Maytenus ilicifolia Leaf Extract Part II-Clinical Study (Phase I).

Maytenus ilicifolia is a plant widely used in South American folk medicine as an effective anti-dyspeptic agent, and the aim of this study was to evaluate their clinical and toxicological effects in healthy volunteers in order to establish its maximum safe dose. We selected 24 volunteers (12 women and 12 men) between 20 and 40 years of age and put them through clinical/laboratory screening and testing to ascertain their psychomotor functions (simple visual reaction, speed and accuracy, finger tapping tests). M. ilicifolia tablets were administered in increasing weekly dosages, from an initial dose of 100 mg to a final dose of 2000 mg. The volunteers' clinical and biochemical profiles and psychomotor functions were evaluated weekly, and they also completed a questionnaire about any adverse reactions. All subjects completed the study without significant changes in the evaluated parameters. The most cited adverse reactions were xerostomia (dry mouth syndrome) (16.7%) and polyuria (20.8%), with reversal of these symptoms without any intervention during the study. The clinical Phase I study showed that the administration of up to 2000 mg of the extract was well tolerated, with few changes in biochemical, hematological or psychomotor function parameters, and no significant adverse reactions. Copyright © 2017 John Wiley & Sons, Ltd.