Morphologic and Pharmacological Investigations in the Epicatechin Gastroprotective Effect

Previous studies of the gastroprotective activity of plants have highlighted the importance of the polyphenolic compound epicatechin (EC) in the treatment of gastric ulcers. This paper aimed to evaluate and characterize the gastroprotective mechanism of action of EC using male rats. The gastroprotective action of EC was analyzed in gastric ulcers induced by ethanol or indomethacin. The involvement of sulfhydryl (SH) groups, K+ATP channels, α2 adrenoceptors, gastric antisecretory activity, and the amount of mucus in the development of gastric ulcers were investigated. The lowest effective dose of EC providing gastroprotective effects was 50 mg/kg in the ethanol-induced gastric ulcers and 25 mg/kg in the indomethacin-induced gastric ulcers. The gastroprotection seen upon treatment with EC was significantly decreased in rats pretreated with a SH compound reagent or an α2-receptor antagonist, but not with a K+ATP channel blocker. Furthermore, oral treatment with EC increased mucus production and decreased H+ secretion. Immunohistochemistry demonstrated the involvement of superoxide dismutase (SOD), nitric oxide (NO), and heat shock protein-70 (HSP-70) in the gastroprotection. These results demonstrate that EC provides gastroprotection through reinforcement of the mucus barrier and neutralization of gastric juice and this protection occurs through the involvement of SH compounds, α2-adrenoceptors, NO, SOD, and HSP-70

Effects of tea from Turnera ulmifolia L. on mouse gastric mucosa support the Turneraceae as a new source of antiulcerogenic drugs

Turnera ulmifolia is a plant belonging to the family Turneraceae, popularly known in Brazil as chanana. This species is distributed from Guyana to southern Brazil where it is considered a weed. The plant occurs in tropical rain forest, fields, and gardens. Chanana tea is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric dysfunction including gastric and duodenal ulcers. In this study, the ability of a lyophilized infusion, as an aqueous fraction (AqF) of the aerial parts of T. ulmifolia, was investigated for its ability to prevent ulceration of the gastric and duodenal mucosa was examined in mice and rats, respectively. The AqF significantly reduced the formation of lesions associated with HCl/ethanol administration by 39% and 46%, respectively, at doses of 500 mg/kg and 1000 mg/kg, p.o. The AqF also significantly reduced the incidence of gastric lesions induced by a combination of indomethacin and bethanechol by 58% and 72% at doses of 500 mg/kg and 1000 mg/kg, respectively. In stress-induced gastric ulcer, the inhibition by the AqF was 48%, 57%, and 58% at doses of 250 mg/kg, 500 mg/kg, and 1000 mg/kg, respectively (p<0.05). A pyloric ligature experiment showed that the highest dose of the AqF significantly affected the gastric juice parameters by increasing the pH from 2.5 (control) to 5.3 and decreasing the acid output from 11.3 (control) to 3.7 mEq/ml/4 h. The AqF had no significant effect on duodenal ulcers induced by cysteamine. Preliminary phytochemical screening confirmed that flavonoids were the major constituents of the AqF of T. ulmifolia. These results indicate that this extract has a significant antiulcerogenic effect, as popularly believed.25448749

Byrsonima Crassa Niedenzu (ik): Antimicrobial Activity And Chemical Study

The methanolic extract of leaves from Byrsonima crassa, a Brazilian medicinal plant, was analyzed by CC and HPLC. Four constituents were isolated and identified as quercetin, methyl gallate, (-)-epigallocatechin gallate and quercetin-3-O-(2″-galloyl)-α-L-arabinopyranoside. The methanolic and hydromethanolic extract, as well as fractions, were evaluated regarding their possible antimicrobial activity using in vitro methods. Results showed that both extracts and fractions exhibited significant antimicrobial activity against all tested strains.2617175Agrawal, P.K., (1989) Carbon 13NMR of Flavonoids, , Amsterdam:ElsevierAlzoreky, N.S., Nakahara, K., Antibacterial activity of extracts from some edible plants commonly consumed in Asia (2003) Int J Food Microbiol, 80, pp. 223-230Amarqiuise, A., Che, C.T., Bejar, E., Malone, M.H., Fong, H.H.S., A New Glycolipid from Byrsonima crassifolia (1994) Planta Med, 60, pp. 85-86Basile, A., Sorbo, S., Giordano, S., Ricciardi, L., Ferrara, S., Montesano, D., Cobianchi, R.C., Ferrara, L., Antibacterial and allelopathic activity of extract from Castanea sativa leaves (2000) Fitoterapia, 71, pp. S110-S116Bauer, A.W., Kirby, M.D.K., Sherries, J.C., Truck, M., Antibiotic susceptibilities testing by standard single disc diffusion method (1966) Am J Clin Pathol, 45, pp. 493-496Bejar, E., Amarquaye, A., Che, C.T., Malone, M.H., Fong, H.H.S., Constituents of Byrsonima crassifolia and their spasmogenic activity (1995) Int J Pharmacog, 33, pp. 25-32Binutu, O.A., Cordell, G.A., Gallic acid derivatives from Mezoneuron benthamianum leaves (2000) Pharm Biol, 38, pp. 284-286Djipa, C.D., Delmee, M., Quetin-Leclercq, J., Antimicrobial activity of bark extracts of Syzygium jambos (L.) Alston (Myrtaceae) (2000) J Ethnopharmacol, 71, pp. 307-313Geiss, F., Heinrich, M., Hunkler, D., Rimpler, H., Heinrich, M., Proanthocyanidins with (+)-epicatechin units from Byrsonima crassifolia bark (1995) Phytochemistry, 39, pp. 635-643Gottlieb, O.R., Henriques Mendes, P., Taveira Magalhães, M., Triterpenoids from Byrsonima verbascifolia (1975) Phytochemistry, 14, pp. 1456-1456Harborne, J.B., (1996) The Flavonoids: Advances in Research since 1986, , New York:Chapman & HallLopez, A., Hudson, J.B., Towers, G.H.N., Antiviral and antimicrobial activities of Colombian medicinal plants (2001) J Ethnopharmacol, 77, pp. 189-196Martínez-Vasquéz, M., González-Esquinca, A.R., Cazares Luna, L., Moreno Gutiérrez, M.N., García-Argáez, A.N., Antimicrobial activity of Byrsonima crassifolia (L.) H.B.K (1999) J Ethnopharmacol, 66, pp. 79-82Mendes, C.C., Cruz, F.G., David, J.M., Nascimento, I.P., David, J.P., Triterpenes esterified with fatty acid and triterpene acids isolated from Byrsonima microphylla (1999) Quím Nova, 22, pp. 185-188Nascimento, G.G.F., Locatelli, J., Freitas, P.C., Silva, G.L., Antibacterial activity of plants extracts and phytochemicals on antibiotic-resistant bacteria (2000) Braz J Microbiol, 31, pp. 247-256(2003) Performance Standards for Antimicrobial Disc Susceptibility Tests, , Approved Standard M2-A7, Pennsylvania:WaynePenna, C., Marino, S., Vivot, E., Cruanes, M.C., Munoz, J.D., Cruanes, J., Ferraro, G., Martino, V., Antimicrobial activity of Argentine plants used in the treatment of infectious diseases. Isolation of active compounds from Sebastiania brasiliensis (2001) J Ethnopharmacol, 77, pp. 37-40Pretorius, J.C., Magama, S., Zietsman, P.C., Purification and identification of antibacterial compounds from Euclea crispa subsp crispa (Ebenaceae) leaves (2003) S Afr J Bot, 69, pp. 579-586Rastrelli, L., De Tommasi, N., Berger, I., Caceres, A., Saravia, A., De Simone, F., Glycolipids from Byrsonima crassifolia (1997) Phytochemistry, 45, pp. 647-650Sannomiya, M., Rodrigues, C.M., Coelho, R.G., Santos, L.C., Hiruma-Lima, C.A., Souza Brito, A.R.M., Vilegas, W., Application of preparative high-speed counter-current chromatography for the separation of flavonoids from the leaves of Byrsonima crassa Niedenzu (IK) (2004) J Chromatogr A, 1035, pp. 47-51Sannomiya, M., Fonseca, V.B., Da Silva, M.A., Rocha, L.R.M., Dos Santos, L.C., Souza, H.C.A., Brito, A.R.M., Vilegas, W., Flavonoids and antiulcerogenic activity from Byrsonima crassa leaves extracts (2005) J Ethnopharmacol, 97, pp. 1-6Silva, S.R., Silva, A.P., Munhoz, C.B., Silva Jr., M.C., Medeiros, M.B., (2001) Guia de Plantas Do Cerrado Utilizadas Na Chapada Dos Veadeiros, , Brasília:WWF58pSrinivasan, D., Nathan, S., Suresh, T., Perumalsamy, P.L., Antimicrobial activity of certain Indian medicinal plants used in folkloric medicine (2001) J Ethnopharmacol, 74, pp. 217-220Wagner, H., Bladt, H., Zgainski, E.M., (1984) Plant Drug Analysis, , Berlin:Springer320

Atividade altiulcerogênica de Indigofera truxillensis Kunth

The genus Indigofera (Fabaceae) is used in folk medicine to treat gastrointestinal pain. In this study, we investigated the antiulcerogenic properties of Indigofera truxillensis Kunth. Oral administration of MeOH extract did not produce any signals of acute toxicity. The antiulcerogenic activity was assessed in different models of acute gastric ulcers (100% ethanol, piroxicam 30 mg.kg-1, hypothermic restraint stress and pylorus ligature) in mice and rats. The animals were treated with the drugs lanzoprazole (30 mg.kg-1) or cimetidine (100 mg.kg-1) as positive controls depending on the performed model. In another experiment with ethanol-induced ulcers in rats, N-ethylmaleimide (NEM), a sulfhydryl group blocker, was also used. The MeOH extract, at doses of 250, 500 and 1000 mg.kg-1, inhibited the gastric lesions in all experiments: a) by 62%, 69% and 32%, respectively, in piroxicam-induced lesions, b) by 43%, 71% and 98%, in ethanol-induced lesions, c) by 69%, 64 and 89%, in hypothermic-restraint stress-induced lesions, d) by 73%, 82% and 84%, in pylorus ligature lesions. Significant changes in the total gastric acid levels were also found after intraduodenal administration of the MeOH extract in the ligated pylorus model. Pre treatment with NEM reduced partially the antiulcerogenic activity of the MeOH extract in ethanol-induced gastric lesions. This result indicates an increase in the levels of non-protein sulfhydryl groups by MeOH extract in the gastric mucosa. These results indicate that the MeOH extract has antisecretory and citoprotective effects that may be related to the presence of flavonoids detected by phytochemical analysis.O gênero Indigofera (Fabaceae) é utilizado na medicina tradicional para distúrbios gastrintestinais. Em nosso trabalho foi investigada a propriedade antiulcerogênica da Indigofera truxillensis Kunth. A administração oral do extrato metanólico (MeOH) não produziu efeitos tóxicos. A atividade antiulcerogênica foi avaliada em diferentes modelos agudos de úlcera gástrica (etanol 100%, piroxicam 30 mg.kg-1, estresse por retenção e frio e ligadura do piloro) em camundongos e ratos. Os animais foram tratados com lansoprazol (30 mg.kg-1) ou cimetidina (100 mg.kg-1), que foram utilizados como controle positivo dependendo do modelo testado. Em outro experimento com úlcera induzida por etanol em ratos, N-etilmaleimida (NEM), um bloqueador dos compostos sulfidríla, também foi utilizado. O extrato metanólico, nas doses de 250, 500 e 1000 mg.kg-1, inibiu significativamente as lesões gástricas em todos os experimentos: a) 62%, 69% e 32%, respectivamente, nas lesões gástricas induzidas por piroxicam, b) 43%, 71% e 98%, nas lesões gástricas induzidas por etanol, c) 69%, 64% e 89%, nas lesões gástricas induzidas por estresse por contenção e frio, d) 73%, 82% e 84%, nas lesões gástricas induzidas por ligadura de piloro. Alterações significativas foram observadas na concentração total de ácido gástrico após a administração via intraduodenal do extrato MeOH no modelo de ligadura do piloro. Pré-tratamento com NEM reduziu parcialmente a atividade antiulcerogênica do extrato MeOH na úlcera induzida por etanol, o que sugere um aumento nos níveis de compostos sulfidríla pelo extrato MeOH na mucosa gástrica. Os resultados indicam que o extrato MeOH possui um efeito antisecretor e citoprotetor, e que tais efeitos podem estar relacionados com a presença de flavonóides detectados por análise fitoquímica no extrato MeOH.00Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Antiulcerogenic activity of four extracts obtained from the bark wood of Quassia amara L. (Simaroubaceae)

Quassia amara L., a neotropical forest shrub of the Simaroubaceae family, is widely used in Caribbean folk medicine and in some northern states of Brazil for the treatment of gastric ulcers. This plant is a source of numerous compounds including both beta-carbonile and cantin-6 alkaloids as well as, primarily, the bitter compounds known as quassinoids. We analyzed the possible antiulcerogenic activities of four extracts of different polarities: 70% ethanol (70% EtOH), 100% EtOH, 100% dichloromethane (DCM), and 100% hexane (HEX) obtained from Quassia amara bark. All extracts, administered at doses of 5000 mg/kg orally and 1000 mg/kg intraperitoneally, caused neither toxicity or death. In the indomethacin[bethanechol-induced gastric ulcer, 70% EtOH, 100% EtOH, DCM and HEX extracts, 100 mg/kg, p.o., inhibited the gastric ulcer (22.5, 23.4, 50.5, 46.8%, respectively). 70% EtOH, 100% EtOH, DCM, and HEX extracts reduced the gastric injury induced by the hypothermic restraint-stress test in mice (70.7, 80, 60, 82.7%, respectively). In the pylorus ligature of the mouse stomach, following pre-treatment with a single intraduodenal administration of 100 mg/kg of each extract, only 70% EtOH did not change the biochemical parameters of gastric juice. 100% EtOH, DCM and HEX extracts presented decreased gastric juice content, increased pH values and decreased acid output. We also determined the antiulcerogenic activity on HCl-EtOH-induced gastric ulcers in mice at four doses (25, 50, 75, 100 mg/kg, p.o.), then evaluated the possible dose-dependent relation and calculated the ED50 values. Except for 70% EtOH at a dose of 25 mg/kg, the other extracts showed significantly activity (p<0.05). The free mucous amount in the gastric stomach content was also evaluated. All extracts showed significant increases (p<0.05) of free mucous. This effect was abolished when the animals were pre-treated with indomethacin. Prostaglandin synthesis was evaluated by the administration of HEX extracts by the oral route (100 mg/kg). Prostaglandin synthesis was significantly, increased by 52.3% (p<0.05), and this effect was abolished with prior administration of indomethacin. We concluded that Quassia amara is a probable source for a new drug to treat gastric ulcers, and the mechanism of its activity relates to cytoprotective factors, such as mucous and prostaglandins, but there is still the possibility that antisecretory activity is involved in its antiulcerogenic effect.2591151115

Cissus Sicyoides: Pharmacological Mechanisms Involved In The Anti-inflammatory And Antidiarrheal Activities

The objective of this study was to evaluate the pharmacological mechanisms involved in anti-inflammatory and antidiarrheal actions of hydroalcoholic extract obtained from the leaves of Cissus sicyoides (HECS). The anti-inflammatory effect was evaluated by oral administration of HECS against acute model of edema induced by xylene, and the mechanisms of action were analysed by involvement of arachidonic acid (AA) and prostaglandin E2 (PGE2). The antidiarrheal effect of HECS was observed and we analyzed the motility and accumulation of intestinal fluid. We also analyzed the antidiarrheal mechanisms of action of HECS by evaluating the role of the opioid receptor, α2 adrenergic receptor, muscarinic receptor, nitric oxide (NO) and PGE2. The oral administration of HECS inhibited the edema induced by xylene and AA and was also able to significantly decrease the levels of PGE2. The extract also exhibited significant anti-diarrheal activity by reducing motility and intestinal fluid accumulation. This extract significantly reduced intestinal transit stimulated by muscarinic agonist and intestinal secretion induced by PGE2. Our data demonstrate that the mechanism of action involved in the anti-inflammatory effect of HECS is related to PGE2. The antidiarrheal effect of this extract may be mediated by inhibition of contraction by acting on the intestinal smoothmuscle and/or intestinal transit. © 2016 by the authors; licensee MDPI, Basel, Switzerland.17

Ulcer healing and mechanism(s) of action involved in the gastroprotective activity of fractions obtained from Syngonanthus arthrotrichus and Syngonanthus bisulcatus

Abstract Background Syngonanthus arthrotrichus and Syngonanthus bisulcatus, currently known for Comanthera aciphylla (Bong.) L.R.Parra & Giul. and Comanthera bisulcata (Koern.) L.R. Parra & Giul, popularly known in Brazil as “sempre-vivas,” are plants from the family Eriocaulaceae. They are found in the states of Minas Gerais and Bahia. The species are known to be rich in flavonoids to which their gastroprotective activity has been attributed. In this research, experimental protocols were performed to elucidate the associated mechanisms of action. Methods The activity was evaluated using induced gastric ulcer models (acetic acid and ethanol-induced gastric lesions in NEM or L-NAME pre-treated mice, and by ischemia/reperfusion). Antioxidant enzymes, serum somatostatin, and gastrin were also evaluated. Results In chronic gastric ulcers, a single daily oral dose of Sa-FRF or Sb-FRF (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. The pre-treatment of mice with NEM (N-ethylmaleimide) or L-NAME (N-nitro-L-arginine) abolished the protective activity of Sa-FRF, Sa-FDF, Sb-FDF and Sb-FRF or Sa-FRF and Sb-FRF, respectively, which indicates that antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective. Sa-FRF and Sb-FRF (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by ischemia/reperfusion (72 and 76 %, respectively). It also decreased lipid peroxidation and restored total thiols in the gastric wall of mice that had been treated with ethanol. When administered to rats submitted to ethanol-induced gastric lesions, Sa-FRF and Sb-FRF (100 mg/kg, p.o.) increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased. Conclusions The results indicate significant healing effects and gastroprotective activity for the Sa-FRF and Sb-FRF, which probably involves the participation of SH groups, nitric oxide (NO), the antioxidant system, somatostatin, and gastrin. All are integral parts of the gastrointestinal mucosa’s cytoprotective mechanisms against aggressive factors

Gastric Ulcers in Middle-Aged Rats: The Healing Effect of Essential Oil from Citrus aurantium

The elderly population has experienced increased life expectancy as well as the increased incidence of gastric ulcers. The peels of fruits from Citrus aurantium L., popularly known in Brazil as orange bitter, are commonly used asatea form for the treatment of gastrointestinal tract disorders, such as ulcer and gastritis. We evaluated the healing effects of essential oil from the peels of Citrus aurantium fruits (OEC) on gastric ulcers in middle-aged rats. We examined the effects of a 14-day chronic OEC treatment on gastric mucosa in middle-aged male Wistar rats that were given acetic-acid-induced gastric lesions by morphometric and immunohistological analyses. Oral OEC treatment significantly reduced the lesion area (76%) within the gastric mucosa and significantly increased (P<.05) the height of regenerated mucosa (59%) when compared to the negative control group. Immunohistochemical analysis of the molecular markers such as COX-2, HSP-70, VEGF, and PCNA in the gastric mucosa confirmed that OEC treatment induced healing effects by increasing the number of new blood vessels and by augmenting gastric mucus in the mucosa glands. These results suggest that the oil from Citrus aurantium effectively heals gastric ulcers in middle-aged animals; however, safe use of OEC demands special care and precautions