RESUMEN
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.
Asunto(s)
Antiulcerosos , Antioxidantes , Flavonoides , Extractos Vegetales , Plantas Medicinales , Ratas Wistar , Úlcera Gástrica , Animales , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/prevención & control , Ratas , Extractos Vegetales/farmacología , Masculino , Antiulcerosos/farmacología , Antiulcerosos/aislamiento & purificación , Plantas Medicinales/química , Antioxidantes/farmacología , Óxido Nítrico/metabolismo , Fabaceae/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Simulación del Acoplamiento MolecularRESUMEN
Eugenia flavescens is a species cultivated in Brazil for food purposes. Given the potential application of essential oils from plants of the genus Eugenia, this study was carried out to investigate the chemical composition, acute toxicity, antioxidant, antinociceptive, gastroprotective activities, and possible mechanisms of action of the essential oil from the leaves of E. flavescens (EOEf). The EOEf was extracted by hydrodistillation, and the chemical composition was obtained using gas chromatography-mass spectrometry. The antioxidant activity was evaluated, as well as the acute toxicity and the antinociceptive and anti-inflammatory effects in mice. In addition, the gastroprotective effect was investigated using an acute gastric lesion model, considering possible mechanisms of action. The major components found in the EOEf were guaiol (19.97%), germacrene B (12.53%), bicyclogermacrene (11.11%), and E-caryophyllene (7.53%). The EOEf did not cause signs of toxicity in the acute oral toxicity test and showed in vitro antioxidant activity with IC50 ranging from 247.29 to 472.39 µg/mL in the tests ABTS and DPPH. In the nociceptive test, EOEf showed a 72.05% reduction in nociception at a dose of 100 mg/kg. In evaluating the anti-inflammatory effect, the essential oil inhibited paw edema by 95.50% and 97.69% at doses of 50 and 100 mg/kg. The results showed that EOEf has a gastroprotective effect, acting through the sulfhydryl compounds (-SH), nitric oxide (NO), and synthesis PGE2 pathways. The results suggested that EOEf is a promising source of constituents with antioxidant, antinociceptive, anti-inflammatory, and gastroprotective properties with application in the food and pharmaceutical industries.
Asunto(s)
Analgésicos , Antiinflamatorios , Antioxidantes , Etanol , Eugenia , Inflamación , Aceites Volátiles , Dolor , Hojas de la Planta , Úlcera Gástrica , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/inducido químicamente , Aceites Volátiles/farmacología , Ratones , Hojas de la Planta/química , Analgésicos/farmacología , Analgésicos/aislamiento & purificación , Antioxidantes/farmacología , Masculino , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Eugenia/química , Inflamación/tratamiento farmacológico , Brasil , Antiulcerosos/farmacología , Antiulcerosos/aislamiento & purificación , FemeninoRESUMEN
Phytol is a diterpene constituent of many essential oils, belonging to the group of unsaturated acyclic alcohols. Although phytol possesses antimycobacterial and anti-inflammatory effects, no reports of a gastrointestinal action are available from the literature. Due to the well-known shortcomings of classical anti-ulcer drugs (e.g. side effects or relapses), natural products may offer an attractive alternative. In this study, a potential gastroprotective activity of phytol was evaluated using acute and chronic ulcer models in rats. Phytol 12.5, 25 and 50 mg/kg, administered orally 1 h prior to induction of gastric lesions by absolute ethanol, inhibited the lesion area by 96, 90 and 95%, respectively. When lesions were induced by ischemia and reperfusion, phytol 12.5 and 25 mg/kg per os decreased the lesion areas by 89 and 46%, respectively. In the third acute ulcer model (lesions induced by ibuprofen), phytol 12.5 mg/kg reduced the lesion area by 55%. Phytol restored the decreased level of reduced glutathione, the increased levels of myeloperoxidase and malondialdehyde and the decreased levels of catalase and superoxide dismutase in rats with gastric ulcer induced by ethanol to levels obtained in vehicle group. Finally, in a chronic model in which gastric ulcer was induced by acetic acid directly instilled into the stomach, phytol administered orally over a time period of 7 days at 12.5, 25, 50 and 100 mg/kg reduced lesion areas by 84, 81, 83 and 68%. Our data suggest a gastroprotective and cicatrizing effect of phytol, possibly associated with its antioxidant effect.
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Antiulcerosos , Modelos Animales de Enfermedad , Etanol , Fitol , Ratas Wistar , Úlcera Gástrica , Animales , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Masculino , Fitol/farmacología , Fitol/uso terapéutico , Ratas , Glutatión/metabolismo , Malondialdehído/metabolismo , Catalasa/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Mucosa Gástrica/metabolismo , Superóxido Dismutasa/metabolismo , Ibuprofeno/farmacología , Ibuprofeno/uso terapéutico , Peroxidasa/metabolismo , Antioxidantes/farmacologíaRESUMEN
INTRODUCTION: Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others. AIMS: To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers. MATERIALS AND METHODS: The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.). RESULTS: MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity. CONCLUSIONS: This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.
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Extractos Vegetales , Hojas de la Planta , Úlcera Gástrica , Animales , Extractos Vegetales/farmacología , Ratones , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Hojas de la Planta/química , Masculino , Antiulcerosos/farmacología , Metanol/química , Género Justicia/química , Modelos Animales de Enfermedad , Cimetidina/farmacología , Acanthaceae/química , Indometacina , Brasil , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patologíaRESUMEN
The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit extracts in gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Scientific articles published between 2010 and 2020 were included in this systematic review, including in vitro and in vivo models, to define the gastroprotective role of fruit extracts. Studies were selected by Rayyan using PubMed, Web of Science, Scopus, and Science Direct databases. The keywords for the search strategy were: "gastric injury," "gastric ulcer," "fruit," "indomethacin," and "aspirin." Twenty-two articles with animal models of gastric ulcers were included. The NSAIDs used were aspirin and indomethacin. To know the damage caused by these, the ulceration index and biomarkers, such as aggressive/defensive factors involved in the gastric ulceration process, were measured. Most studies have shown that fruit extracts have antiulcer activity, with the most abundant metabolites being flavonoids, followed by terpenes and alkaloids. Possible antiulcer activities such as antioxidant, cytoprotective, gastric acid antisecretory, anti-inflammatory, or angiogenesis stimulant were declared, manifested mainly as a reduction of lipid peroxidation products, an increase in antioxidant enzymes and prostaglandins, and by the formation of a protective film through protein precipitation in the ulcer area. This systematic review demonstrates the importance of fruit extracts as gastric protectors.
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Antiulcerosos , Úlcera Gástrica , Ratas , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Antioxidantes/metabolismo , Frutas/metabolismo , Mucosa Gástrica/metabolismo , Extractos Vegetales/uso terapéutico , Ratas Wistar , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Indometacina/efectos adversos , Aspirina/efectos adversos , Aspirina/metabolismoRESUMEN
Licania rigida Benth., a Brazilian endemic plant, has been traditionally used for treating inflammation and stomach pain. This work investigates the anti-inflammatory and gastroprotective activities of the ethanolic extract from L. rigida seeds (EELr) by in vitro and in vivo methods. The phytochemical profile was determined and the in vitro antioxidant activity was investigated by radical scavenging and thiobarbituric acid reactive substances methods. The ovalbumin denaturation method was used with sodium diclofenac as standard for the in vitro anti-inflammatory activity assessment. Acetylsalicylic acid was used to induce gastric ulcers in male mice and then to evaluate the preventive and therapeutic gastroprotective effect of EELr, using omeprazole as the reference drug. The extract exhibited relevant amount of phenolic compounds and flavonoids, in particular, demonstrating in vitro antioxidant capacity. EELr was able to inhibit almost 60% of ovalbumin denaturation at a concentration considered low. It also prevented the decrease of biochemical markers for oxidative stress such as superoxide dismutase (SOD) and reduced glutathione (GSH) in the stomach and SOD and catalase (CAT) in the liver. EELr also significantly decreased the number of lesions as well as reduced the ulcerated area when used as therapy. The observed effect may be due to its phenolic compounds, such as chlorogenic acid, caffeic acid and tannins, as previously reported. EELr is a potential source of compounds with anti-inflammatory activity, protects the liver from oxidative damage and improves healing of aspirin-induced ulcers. This work contributes to the knowledge of L. rigida species.
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Antiulcerosos , Chrysobalanaceae , Úlcera Gástrica , Ratas , Ratones , Animales , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Fitoterapia , Chrysobalanaceae/química , Ovalbúmina/farmacología , Ratas Wistar , Antiulcerosos/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Etanol/química , Aspirina/farmacología , Semillas , Superóxido Dismutasa , Mucosa GástricaRESUMEN
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.
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Antiulcerosos , Artemisia absinthium , Plantas Medicinales , Úlcera Gástrica , Ratas , Animales , Extractos Vegetales/efectos adversos , Ratas Wistar , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Mucosa Gástrica , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Etanol/farmacología , FitoterapiaRESUMEN
Gastrointestinal diseases, such as peptic ulcers, are caused by a damage in the gastric mucosa provoked by several factors. This stomach injury is regulated by many inflammatory mediators and is commonly treated with proton-pump inhibitors, histamine H2 receptor blockers and antacids. However, various medicinal plants have demonstrated positive effects on gastric ulcer treatment, including plants of the Ceiba genus. The aim of this study was to evaluate the antiulcer and anti-inflammatory activities of the stem bark ethanolic extract of Ceiba speciosa (A. St.-Hil.) Ravenna. We performed a preliminary quantification of phenolic compounds by high-performance liquid chromatography-diode array detection (HPLC-DAD), followed by the prospection of other chemical groups through nuclear magnetic resonance (NMR) spectroscopy. A set of in vitro assays was used to evaluate the extract potential regarding its antioxidant activity (DPPH: 19.83 ± 0.34 µg/mL; TPC: 307.20 ± 6.20 mg GAE/g of extract), effects on cell viability and on the release of TNF-α in whole human blood. Additionally, in vivo assays were performed to evaluate the leukocyte accumulation and total protein quantification in carrageenan-induced air pouch, as well as the antiulcerogenic effect of the extract on an ethanol-induced ulcer in rats. The extract contains flavonoids and phenolic compounds, as well as sugars and quinic acid derivatives exhibiting potent antioxidant activity and low toxicity. The extract reduced the release of TNF-α in human blood and inhibited the activity of p38α (1.66 µg/mL), JAK3 (5.25 µg/mL), and JNK3 (8.34 µg/mL). Moreover, it reduced the leukocyte recruitment on the pouch exudate and the formation of edema, reverting the effects caused by carrageenan. The extract presented a significant prevention of ulcer formation and a higher reduction than the reference drug, Omeprazole. Therefore, C. speciosa extract has demonstrated relevant therapeutic potential for the treatment of gastric diseases, deserving the continuation of further studies to unveil the mechanisms of action of plant bioactive ingredients.
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Antiulcerosos , Ceiba , Extractos Vegetales , Úlcera Gástrica , Animales , Humanos , Ratas , Antiulcerosos/farmacología , Antioxidantes/farmacología , Carragenina/efectos adversos , Ceiba/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismo , ÚlceraRESUMEN
Campomanesia reitziana D. Legrand (Myrtaceae) displays antiulcer properties when given to rodents. The major active chemical components of C.â reitziana are chalcones, including 4',6'-dihydroxy-2'-methoxy-3',5'-dimethylchalcone or dimethyl cardamonin (DMC); therefore, we hypothesized that this compound could have antiulcer effects and the present study aimed to evaluate its gastroprotective and gastric healing properties. DMC was isolated from the fruits of C.â reitziana, and its gastroprotective effect was evaluated by ethanol and indomethacin-induced gastric ulcer models in mice (0.1â mg/kg, i.p. and 1 and 3â mg/kg, p.o.). Oxidative stress and inflammatory parameters were analyzed in the gastric tissue. Moreover, its gastric healing effect was evaluated in rats. In addition, the compound's mode of action was evaluated inâ vivo and inâ vitro by measuring H+ -K+ -ATPase activity. Finally, the cytotoxic potential of DMC was tested in fibroblasts and human gastric adenocarcinoma cells. The DMC reduced the ethanol-induced gastric ulcer in mice by 77 %, increased the adhered mucus, and reduced lipoperoxides levels. The block of nonprotein sulfhydryls (NP-SH) compounds by pretreatment with N-ethylmaleimide (NEM), the inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), or the antagonism of α2 receptor using yohimbine reversed the gastroprotective effects of DMC. Furthermore, DMC reduced the acidity of gastric content in pylorus-ligated rats but did not change H+ , K+ -ATPase (isolated from rabbit) activity inâ vitro. DMC reduced the lesion area in acetic acid-induced ulcers and decreased myeloperoxidase activity. DMC did not change the viability of fibroblast cells (L929) but reduced the viability of human gastric adenocarcinoma cells (AGS). The results confirmed that DMC could significantly enhance the gastric healing process and prevent ulcers due to improving protective factors on the gastric mucosa and reducing gastric acid secretion.
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Antiulcerosos , Chalconas , Myrtaceae , Úlcera Gástrica , Humanos , Ratas , Ratones , Animales , Conejos , Chalconas/farmacología , Chalconas/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Roedores , Úlcera/tratamiento farmacológico , Frutas , Ratas Wistar , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Antiulcerosos/química , Etanol , Adenosina TrifosfatasasRESUMEN
Preparations of Helicteres sacarolha (Malvaceae) leaves and roots are used in the form of decoction, infusion or maceration, to treat gastrointestinal disturbances, among others. Studies supporting some of its ethnomedicinal uses are still incipient. The present study aimed to investigate it potential effect on chronic ulcer, ulcerative colitis and possible prokinetic activities as part of its mechanism of action. The powdered leaves of Helicteres sacarolha (HEHs) was prepared by maceration in 70 % hydroethanolic solution. Its qualitative phytochemical constituents were investigated by direct flow injection analysis coupled to atmospheric pressure chemical ionization ion trap tandem mass spectrometry (FIA-APCI-IT-MSn ). The gastric ulcer healing effect was evaluated in acetic acid induced chronic ulcer in mice and the lesions were evaluated, including analysis of blood plasma cytokine levels. The prokinetic properties (gastric emptying and intestinal transit) were carried out in mice. Potential anti-ulcerative colitis activity was evaluated in rats using 2,4,6-trinitrobenzenesulfonic acid (5 % TNBS) -induced colitis. All animal experiments were carried out at the doses of 20, 50 and 250â mg/kg (p.o.). Eight compounds were putatively identified, specifically lariciresinol, and its derivatives, kaempferol derivatives and Tricin-O-Glc. The extract promoted increased gastric ulcer healing at all doses tested. Modulation of the cytokines involved inhibition of some key pro-inflammatory cytokines with maximum effect on IL-1ß (70 %, 50â mg/kg, p<0.05), TNF-α (79 %, 20â mg/kg, p<0.01), and in the anti-inflammatory cytokines, namely IL-10 (57 %, 50â mg/kg, p<0.05) and IL-17 (79 %, only at 50â mg/kg, p<0.05). Histological findings demonstrated a mitigated inflammatory activity, and tissues undergoing regeneration. HEHs treatment caused delayed gastric emptying, and increased intestinal transit, but had no effect in the experimentally induced ulcerative colitis. We report for the first time putatively the presence of Lariciresinol and tricin derivatives from the hydroethanolic leaves extract of H. sacarolha. Its possible mechanism of actions of gastric ulcer healing involves cytokines modulation, mitigation of inflammatory response and tissue regeneration and provoked opposing effect in the gastrointestinal system. The present study demonstrates the therapeutic potential of H. sacarolha leaves used in Brazilian ethnomedicine in the treatment of chronic gastric ulcer.
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Antiulcerosos , Malvaceae , Úlcera Gástrica , Ratas , Ratones , Animales , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Citocinas , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Fitoterapia/métodos , Ratas Wistar , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Antiulcerosos/química , Malvaceae/químicaRESUMEN
BACKGROUND: Geraniol (GE) is dietary acyclic monoterpene alcohol found in essential oils from aromatic plants with therapeutic value against gastric ulcers already described. HYPOTHESIS/PURPOSE: To assess whether oral GE accelerates gastric healing or prevents ulcer recurrence, and to evaluate the hypothesis that GE promotes antiulcer effects by the inhaled route and that promotes changes in the behavior of ulcerated rodents. METHODS: Gastric healing effects, underlining mechanisms, and behavioral changes were measured in80% acetic acid-induced gastric ulcer model in rats receiving GE by oral (30 mg/kg) or inhaled route (1 mg/L of air/min); whereas the effects of GE to avoid ulcer recurrence was evaluated in mice submitted to 10% acetic acid plus IL-1ß ulcer. RESULTS: GE administered by both routes accelerates gastric healing, increasing mucin and GSH levels, CAT, and GST activities, and reducing MPO activity. Moreover, oral, and inhaled GE minimized ulcer recurrence reducing gastric TNF and IL-6 levels and preserving mucin levels. Interestingly, the inhalation or oral intake of GE promotes anxiolytic-like effects in ulcerated rats. CONCLUSION: Data altogether suggest that the GE accelerates gastric healing through the strengthening of protective factors of the gastric mucosa, promoting a quality healing that reduces the recurrence of the lesion. Besides, the anxiolytic-like effect of GE may also contribute to its gastric healing action since anxiety is recognized as one of the etiologic agents of ulcers.
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Monoterpenos Acíclicos , Ansiolíticos , Antiulcerosos , Úlcera Gástrica , Animales , Ratones , Ratas , Ácido Acético , Monoterpenos Acíclicos/farmacología , Ansiolíticos/farmacología , Antiulcerosos/farmacología , Mucosa Gástrica , Mucinas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
CONTEXT: The gastroprotective effect of Heliotropium indicum L. (Boraginaceae), a plant traditionally used in Mexico to treat gastric ulcers, has been previously reported. However, no active compound was identified. OBJECTIVE: The current contribution aimed to isolate, through a bioassay-guided study, at least one compound from H. indicum with considerable gastroprotective activity, examine its effect on ethanol-induced gastric lesions in mice, and explore possible mechanisms of action. MATERIALS AND METHODS: Three extracts (hexane, dichloromethane, and methanol) were obtained from H. indicum leaves. Their 30 and 100 mg/kg doses were assessed on ethanol-induced gastric lesions in male CD1 mice. Since the dichloromethane extract was the most active, successive chromatographies were carried out leading to the identification of the most active compound. This compound (at 3-100 mg/kg) was compared to carbenoxolone (at 10-100 mg/kg) in biological evaluations in mice. Pre-treatments with indomethacin (10 mg/kg, s.c.), L-NAME (70 mg/kg, i.p.), and NEM (10 mg/kg, s.c.) were performed independently to determine the participation of prostaglandins, nitric oxide, and/or sulfhydryl groups, respectively, in the mechanism of action of the compound. RESULTS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from H. indicum, afforded dose-dependent gastroprotective activity. The maximum effect was observed at 100 mg/kg (90.13 ± 3.08%), with an ED50 of 5.92 ± 2.48 mg/kg. Gastroprotection was not modified by pre-treatment with indomethacin, L-NAME, or NEM. CONCLUSIONS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, isolated from H. indicum, was found to produce a substantial gastroprotective effect. Prostaglandins, nitric oxide, and non-protein sulfhydryl groups are not involved in its mechanism of action.
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Antiulcerosos , Heliotropium , Animales , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Etanol , Indometacina/farmacología , Masculino , Cloruro de Metileno , Ratones , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico , Prostaglandinas , Ratas , Ratas Wistar , Compuestos de SulfhidriloRESUMEN
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.
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Antiulcerosos , Úlcera Péptica , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Antagonistas de los Receptores H2 de la Histamina/farmacología , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Úlcera Péptica/tratamiento farmacológico , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
Found in humid regions and waterways and popularly used to treat gastrointestinal problems among other applications, the present study evaluated the M. aquatica essential oil (OEMa) as a therapeutic alternative to treat gastrointestinal disorders. Produced by steam distillation, chemical composition of OEMa was determined by GC-MS analysis. The ethanol-induced ulcer and the dose-repeated acetylsalicylic acid (ASA)-induced gastrointestinal lesions models in rats evaluated, respectively, the prophylactic and curative effects of EOMa on peptic ulcers. The EOMa's effect on gastric secretion, gastric mucus and gastrointestinal motility were evaluated in in vivo models. The curative effect of EOMa on acute colitis was evaluated using the DSS-induced colitis model in mice. Obtained in 0.17% yield (w/w), with carvone (54.82 ± 1.39 g/100 g oil) as the main constituent, EOMa (at 75 mg/kg) showed potent gastroprotective effect (> 90%) mediated by non-protein sulfhydryl compounds (NPSH) and nitric oxide (NO) modulation alongside reduction in gastric secretion volume and total acidity. EOMa did not affect gastric mucus production and gastrointestinal motility. In dose-repeated ASA-induced gastrointestinal lesions model, EOMa (at 25 mg/kg) promoted the inflammatory process resolution both in gastric and duodenal walls by modulating NPSH, NO and myeloperoxidase levels. Despite delaying in 2 days the clinical symptoms worsening, EOMa (at 25 mg/kg) was not able to protect colon tissues from DSS-induced acute colitis as evidenced by macroscopic, biochemical, and histopathological parameters. This is the first report of Mentha aquatica essential oil as a promising herbal medicine for peptic ulcers treatment together with an adjuvant effect in IBD.
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Antiulcerosos , Colitis , Mentha , Aceites Volátiles , Úlcera Péptica , Úlcera Gástrica , Ratas , Ratones , Animales , Aceites Volátiles/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Antiulcerosos/farmacología , Mucosa Gástrica , Ratas Wistar , Úlcera Péptica/tratamiento farmacológico , Extractos Vegetales/farmacología , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/patologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The use of mushrooms in medicine is quite old and the first report about the use of genus Agaricus in treatment of ulcers occurred in Byzantine period. This mushroom is widely consumed as food, tea, food supplements, as well as nutraceutical and cosmeceutical applications, being cultivated and appreciated in several countries such as Brazil, Korea, Japan and China. AIM OF THE STUDY: This study aimed to characterize the chemical profile and the potential gastroprotective effect of hydroalcoholic extract from Agaricus blazei Murill (HEAb). MATERIALS AND METHODS: The extract was chemically characterized by elemental analysis, UPLC-QTOF-MSE, Nuclear Magnetic Resonance (NMR) and high-performance liquid chromatography (HPLC) techniques to elucidate the metabolites present in the extract. The quantification of phenolic compounds and the in vitro antioxidant activities were performed and the gastroprotective effect of this extract was evaluated against ethanol-induced gastric ulcer model. HEAb was administered by gavage at 5, 25 and 50 mg kg-1 and N-acetylcysteine at 300 mg kg-1 (positive control). Furthermore, the pathways of nitric oxide (NO), Cyclic Guanylate Monophosphate (cGMP), prostaglandins (PGs) and the involvement of ATP-sensitive K+ Channels were modulated. RESULTS: Mannitol, malic acid, pyroglutamic acid, L-agaritine and L-valine were putatively identified by UPLC-QTOF-MSE in HEAb. In addition, it was possible to identify mannitol by the intense signals in the NMR spectra, being still quantified as the main compound in the extract by HPLC. The contents of total phenols and flavonoids corroborated with the good antioxidant activity of HEAb. This study observed that HEAb at 25 and 50 mg kg-1 had gastroprotection effect demonstrated by the reduction of histopathological parameters and the reduction of mastocytosis in the stomach of mice. CONCLUSIONS: In this study was possible to conclude that HEAb has gastroprotective effect related to the involvement of NO and PG pathways in the ethanol-induced gastric ulcer model in mice.
Asunto(s)
Agaricus , Antiulcerosos , Úlcera Gástrica , Agaricus/metabolismo , Animales , Antiulcerosos/química , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Etanol/química , Mucosa Gástrica , Manitol/metabolismo , Manitol/farmacología , Manitol/uso terapéutico , Ratones , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & controlRESUMEN
BACKGROUND: Gastric ulcer has been a major cause of morbidity and mortality worldwide, and it has been linked to factors such as nutritional deficiency, smoking, stress, and continuous intake of non-steroidal antiinflammatory drugs (NSAIDs). The search for new anti-ulcer therapeutic agents has been the subject of several studies. Recently, the gastroprotective effect of Celtis iguanaea has been reported, with linoleic acid (LA) responsible for many of the therapeutic effects of this medicinal plant. AIMS: This study aims to investigate the gastroprotective activity and the possible mechanisms in which LA may be involved through different experimental assays in mice. METHODS: The gastroprotective activity of LA was evaluated in the ulcer induced by indomethacin, HCl/EtOH, hypothermic-restraint stress and pyloric ligation. For the investigation of gastroprotective mechanisms, the quantification of the volume (mL), pH and total acidity of gastric secretion were considered. RESULTS: The oral administrations of 25 mg/kg, 50 mg/kg or 100 mg/kg of body weight of LA were capable of protecting the gastric mucosa against HCl/ethanol (10 mL/kg p.o.), and oral/intraduodenal treatment administrations of 50 mg/kg LA showed protection from ulcers induced by indomethacin, hypothermic-restraint stress and pyloric ligation. CONCLUSION: The results of this study show the gastroprotective role of LA in gastric mucosal damage induced by all assayed distresses. The observed gastroprotection possibly occurs due to the mediated increase of mucosal defensive factors.
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Antiulcerosos , Úlcera Gástrica , Animales , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Modelos Animales de Enfermedad , Etanol/efectos adversos , Mucosa Gástrica , Humanos , Indometacina/efectos adversos , Ácido Linoleico/efectos adversos , Ratones , Extractos Vegetales/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs8-13(L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non- ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski's rule of five. A molecular docking study showed that the hybrids8-13(L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.
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Antiinflamatorios no Esteroideos/farmacología , Antiulcerosos/farmacología , Edema/tratamiento farmacológico , Peritonitis/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/farmacología , Úlcera/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Antiulcerosos/síntesis química , Antiulcerosos/química , Carragenina , Celecoxib/química , Celecoxib/farmacología , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Lignanos/química , Lignanos/farmacología , Masculino , Ratones , Estructura Molecular , Peritonitis/inducido químicamente , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/química , Ratas , Relación Estructura-Actividad , Triazoles/química , Triazoles/farmacología , Úlcera/inducido químicamenteRESUMEN
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.
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Antiulcerosos/farmacología , Antioxidantes/farmacología , Apiterapia , Própolis/farmacología , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Mucosa Gástrica/efectos de los fármacos , Humanos , Úlcera Gástrica/inducido químicamente , Resultado del TratamientoRESUMEN
Artemisia ludoviciana subsp. mexicana has been traditionally used for the treatment of digestive ailments such as gastritis, whose main etiological agent is Helicobacter pylori. In a previous screening study, the aqueous extract exhibited a good in vitro anti-H. pylori activity. With the aim of determining the efficacy of this species as a treatment for H. pylori related diseases and finding bioactive compounds, its aqueous extract was subjected to solvent partitioning and the fractions obtained were tested for their in vitro anti-H. pylori effect, as well as for their in vivo gastroprotective and anti-inflammatory activities. The aqueous extract showed a MIC = 250 µg/mL. No acute toxicity was induced in mice. A gastroprotection of 69.8 ± 3.8%, as well as anti-inflammatory effects of 47.6 ± 12.4% and 38.8 ± 10.2% (by oral and topical administration, respectively), were attained. Estafiatin and eupatilin were isolated and exhibited anti-H. pylori activity with MBCs of 15.6 and 31.2 µg/mL, respectively. The finding that A. ludoviciana aqueous extract has significant anti-H. pylori, gastroprotective and anti-inflammatory activities is a relevant contribution to the ethnopharmacological knowledge of this species. This work is the first report about the in vivo gastroprotective activity of A. ludoviciana and the anti-H. pylori activity of eupatilin and estafiatin.
Asunto(s)
Artemisia/metabolismo , Flavonoides/farmacología , Helicobacter pylori/efectos de los fármacos , Animales , Antiulcerosos/farmacología , Flavonoides/metabolismo , Gastritis/tratamiento farmacológico , Masculino , Medicina Tradicional , Ratones , Ratones Endogámicos , Extractos Vegetales/farmacología , Sesquiterpenos/metabolismo , Sesquiterpenos/farmacología , Úlcera Gástrica/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.