RESUMO
Copaifera pubiflora Benth oleoresin (CPO) is used as an anti-inflammatory, wound healing, and antimicrobial. This paper reports the cytotoxic, anti-inflammatory, and antinociceptive activities of CPO. CPO (10 mg/kg) did not affect locomotor capacity in the open-field and rotarod tests and was not cytotoxic to CHO-k1, THP-1, and L929 cell lines. It was active in the formalin test at 3 mg/kg by 86 ± 3% and 96 ± 3%, respectively, for the first and second phases. At 10 mg/kg, CPO inhibited 90 ± 7%, the pain in the mechanical hyperalgesia test. In the tail-flick test, CPO at 3 mg/kg affected the tail-flick latencies in mice by 77 ± 20%, which in combination with naloxone was only partially reduced. At 3 mg/kg CPO inhibited 80 ± 12% the carrageenan-induced paw edema, and at 3 mg/kg it reduced by 91 ± 5% the nociception on acetic acid-induced abdominal writhing. Therefore, CPO possesses anti-inflammatory and antinociceptive activities.
Assuntos
Analgésicos , Fabaceae , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The p-coumaric acid is a phenolic compound present in large quantities in the extract of Baccharis dracunculifolia DC, a Brazilian medicinal plant used to treat gastric ulcer. Given the necessity for finding new chemical components capable of accelerating gastric healing, in this study, the effects of the p-coumaric acid were evaluated in the acetic acid-induced ulcer model in rats, where histological, inflammatory, and oxidative parameters were analyzed. The healing property was also evaluated in the scratch assay on fibroblast cells (L929) and the cytotoxicity of p-coumaric acid was assessed in both L929 and human gastric adenocarcinoma (AGS) cells by MTT assay. The treatment with p-coumaric acid (10 mg/kg, p.o.) for 7 days, twice a day, decreased by 44.6% the acetic acid-induced gastric ulcer compared with the vehicle-treated group. The vehicle control-treated group showed a larger extension of the ulcer base and an extensive damage into the mucosa and submucosa layers, which were mitigated by the treatment with p-coumaric acid. This beneficial effect was also associated with increased levels of mucin and reduced glutathione, decreased amount of lipid hydroperoxides, and increased superoxide dismutase and catalase activities without interfering with the activity of myeloperoxidase in the gastric tissue. The compound promoted the restructuring of the cell monolayer in the scratch test and did not show toxicity in the L929 cell line, while reduced the viability of the AGS, a lineage of human gastric adenocarcinoma. Thus, p-coumaric acid may be considered a natural source for the treatment of gastric ulcers, by reinforcing protective factors of gastric mucosa and by accelerating gastric healing.
Assuntos
Antiulcerosos/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Ácido Acético , Animais , Antiulcerosos/farmacologia , Baccharis/química , Catalase/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácidos Cumáricos/isolamento & purificação , Ácidos Cumáricos/farmacologia , Modelos Animais de Doenças , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa/metabolismo , Humanos , Camundongos , Peroxidase/metabolismo , Fitoterapia , Ratos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has been used in folk medicine to treat gastric disorders for centuries. However, although studies have been conducted to validate the gastroprotective and anti-ulcer activity of some types of propolis, red propolis activity remains unknown. AIM OF THE STUDY: The present study aimed to evaluate the gastroprotective effect of the hydroalcoholic extract of red propolis (HERP), its mode of action, and the main compounds involved in its activity, therefore contributing to validate the chemical and pharmacological potential of this product. MATERIAL AND METHODS: The effect of HERP (30, 100 and 300 mg/kg p.o. and 30 mg/kg i.p.), and the isolated compounds vestitol (VS), neovestitol (NV), methylvestitol (MV), medicarpin (MD), and oblongifolin AB (OB) (10 mg/kg p.o.) were evaluated on gastric ulcers induced by 60% ethanol/0.3 M HCl (5 mL/kg, p.o.) in mice. Histological changes and mucin levels were assessed by HE and PAS, respectively. Moreover, oxidative stress parameters and myeloperoxidase activity were analyzed on ulcerated tissue. The effect of HERP on gastric acid secretion was evaluated by pyloric ligature model and the mechanisms involved in its gastroprotective effect were investigated by pretreating mice with L-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a non-selective cyclooxygenase inhibitor, 10 mg/kg, i.p.). RESULTS: HERP (300 mg/kg p.o. or 30 mg/kg i.p.), MV, and MD (10 mg/kg p.o.) protected gastric mucosa against the damage induced by ethanol/HCl. Histological changes were attenuated by the HERP, MV, and MD. Moreover, HERP and MV increased mucin levels. Besides, oxidative stress and MPO activity were reduced by the three treatments. HERP did not display anti-secretory action, but its effect was abolished by indomethacin treatment. CONCLUSIONS: HERP displays gastroprotective property against ethanol/HCl-induced damage. Its effect is dependent on prostaglandins and mucin production. The compounds MV and MD may have an essential role in the activity of HERP. Our data contribute to validate the traditional use of propolis for gastric disorders.
Assuntos
Antiulcerosos/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Própole , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/isolamento & purificação , Brasil , Modelos Animais de Doenças , Etanol , Ácido Gástrico/metabolismo , Mucinas Gástricas/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Própole/química , Prostaglandinas/metabolismo , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologiaRESUMO
Gomphrena celosioides Mart. (Amaranthaceae) is used in folk medicine as a natural analgesic, and in Brazil, the species of genus Gomphrena is used for rheumatism. However, scientific evidence which supports its popular use as an analgesic is scarce. This study assessed the antiarthritic and antihyperalgesic activities of the ethanolic extract obtained from G. celosioides aerial parts on Swiss or C57BL/6 mice. The antiarthritic and antihyperalgesic potential of Gomphrena celosioides was evaluated using paw edema, mechanical hyperalgesia, cold allodynia, carrageenan-induced pleurisy, articular inflammation zymosan-induced, Freund's complete adjuvant-induced inflammation zymosan-induced peritonitis, and carrageenan-induced adhesion and rolling experiment models. All doses of G. celosioides (300, 700, and 1000 mg/kg) significantly reduced edema formation in all the intervals evaluated, whereas the mechanical hyperalgesia was reduced 3 hours after the carrageenan injection. The cold hyperalgesia was significantly decreased 3 (700 mg/kg) and 4 hours (700 and 1000 mg/kg) after the carrageenan injection. Ethanolic extract of G. celosioides at 1000 mg/kg reduced the total leukocyte number, without interfering in the protein extravasation in carrageenan-induced pleurisy model. Ethanolic extract of G. celosioides (300 mg/kg) was also able to reduce significantly the leukocyte migration in zymosan-induced articular edema, while a reduction of the adhesion and migration and leukocyte rolling was induced by the ethanolic extract of G. celosioides (300 mg/kg) in zymosan-induced peritonitis. In Freund's complete adjuvant-induced inflammation model, an edema formation and mechanical hyperalgesia reduction were induced by the ethanolic extract of G. celosioides on day 22, whereas the cold allodynia was reduced on day 6 of treatment with the extract. These results show that ethanolic extract of G. celosioides has antihyperalgesic and antiarthritic potential in different acute and persistent models, explaining, at least in part, the ethnopharmacological relevance of this plant as a natural analgesic agent.
RESUMO
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.
Assuntos
Antiulcerosos/farmacologia , Jatropha/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/isolamento & purificação , Brasil , Linhagem Celular Tumoral , Diterpenos , Feminino , Masculino , Medicina Tradicional , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Sesquiterpenos , Úlcera Gástrica/induzido quimicamente , Testes de Toxicidade AgudaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus robusta Reissek (Celesteraceae), popularly named as cafezinho do mato or coração de bugre, is employed to treat inflammatory digestive diseases in the south of Brazil. However, despite popular usage, the effects of this species on an experimental model of ulcerative colitis are unknown. AIM OF THE STUDY: To evaluate the effects of M. robusta extract (HEMR) on colon and liver from mice with colitis induced by dextran sulfate sodium (DSS). MATERIALS AND METHODS: Firstly, the cytotoxicity of HEMR and its effects on ROS and nitrite production in IEC-6 cells were evaluated. The experimental colitis was established by adding 3% DSS on drinking water of mice and the effects of HEMR (1-100 mg/kg, p.o, once a day by 7 days) in colonic and hepatic tissues were analyzed. RESULTS: The HEMR (1-100 µg/mL) did not alter the cell viability but reduced nitrite production of IEC-6 stimulated by LPS. Moreover, HEMR (100 mg/Kg) attenuates macro and microscopic alterations in the colon from mice exposed to DSS, as evidenced by a reduction of the colon shortening, attenuation of the epithelial erosion, submucosal edema and preservation of the Goblet cells integrity, as well as the restoration of mucin depletion. The treatment with HEMR increased GSH amount, reduced LOOH levels and normalizes CAT activity in the colon. The group treated with HEMR showed increased GST activity, reduced MPO activity and decreased inflammatory cytokines secretion (TNF and IL-6) in the colonic tissue. In the liver, HEMR increased GST activity, decreased the GPx activity and reduced IL-6 levels. Furthermore, the HEMR treatment reduced AST and ALT serum levels in mice exposed to DSS. Finally, the HEMR was able to reduce intestinal transit. CONCLUSIONS: HEMR treatment minimizes inflammation of the colon and maintaining the antioxidant homeostasis. In addition, HEMR may be a potential tool to prevent hepatic injury secondary to ulcerative colitis.
Assuntos
Anti-Inflamatórios/farmacologia , Colite/prevenção & controle , Colo/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Maytenus , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/farmacologia , Linhagem Celular , Colite/induzido quimicamente , Colite/metabolismo , Colite/patologia , Colo/metabolismo , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Fármacos Gastrointestinais/isolamento & purificação , Motilidade Gastrointestinal/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Fígado/metabolismo , Maytenus/química , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , RatosRESUMO
OBJECTIVES: Açaí (Euterpe oleracea) is widely consumed in Brazil and known for its numerous health-beneficial properties. This study investigated the gastroprotective potential of the dried açaí berries extract (DAE). METHODS: Dried açaí berries extract effect was evaluated against ethanol-induced gastric ulcer in rats. Its ability to regulate antioxidant defenses and reduce inflammatory parameters was evaluated in the ulcerated tissues. The scavenger capability of DAE was assessed by DPPH assay, and phytochemical composition was accessed by UHPLC. KEY FINDINGS: The extract showed radical scavenger activity in vitro (IC50 = 210 µg/ml) and gastroprotective effect in vivo, reducing the ulcerated area by 83%, 67% and 48% at doses of 30 and 100 mg/kg (p.o) and 3 mg/kg (i.p), respectively, compared with vehicle group. Besides, DAE (100 mg/kg, p.o) increased the GSH content and GST activity in ulcerated mucosa. Animals treated with DAE showed normalized levels of SOD activity, elevated CAT activity and decreased MPO activity, as well as reduced TNF-α levels, compared with vehicle group. Peonidin-3-glucoside, peonidin-3-rutinoside, cyanidin-3,5-hexoside-pentoside, cyaniding-3-glucoside, pelargonidin-3-glucoside and pelargonidin-3-rutinoside were identified in DAE. CONCLUSIONS: Our findings suggest that DAE reduces the inflammation and maintains the oxidative balance of gastric mucosa, therefore being a promising natural resource or useful nutraceutical to protect gastric mucosa.
Assuntos
Euterpe/química , Sequestradores de Radicais Livres/farmacologia , Extratos Vegetais/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Antioxidantes/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/toxicidade , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/patologia , Concentração Inibidora 50 , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Chronic wounds constitute a serious public health problem, and developing pharmaceutical dosage forms to ensure patient comfort and safety, as well as optimizing treatment effectiveness, are of great interest in the pharmaceutical, medical and biomaterial fields. In this work, the preparation of films based on blends of poly(vinyl alcohol), starch and poly(acrylic acid), polymers widely used as pharmaceutical excipients, and pomegranate peel extract (PPE), a bioactive compound with antimicrobial and healing activities relevant to the use as a bioactive wound dressing, was proposed. Initially, the minimum inhibitory concentration (MIC) of the PPE was investigated by an in vitro method. Then, the best concentration of the PPE to be used to prepare the films was researched using an antimicrobial susceptibility test with the disc diffusion method. The microbiological assay was performed in films prepared by the solvent casting method in the presence of two concentrations of PPE: 1.25% w/v and 2.5% w/v. Films containing the lower PPE concentration showed antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis, with a difference that was not considered statistically significant when compared to the higher concentration of the extract. Therefore, the films prepared with the lower proportion of PPE (1.25% w/v) were considered for the other studies. The miscibility and stability of the extract in the films were investigated by thermal analysis. Parameters that determine the barrier properties of the films were also investigated by complementary techniques. Finally, in vitro biological tests were performed for safety evaluation and activity research. Analysis of the results showed that the incorporation of the higher proportion of starch in the blend (15% v/v) (PVA:S:PAA:PPE4) yielded smooth, transparent, and domain-free films without phase separation. Additionally, the PVA:S:PAA:PPE4 film presented barrier properties suitable for use as a cover. These films, when subjected to the in vitro hemolytic activity assay, were nonhemolytic and biocompatible. No toxicity from the extract was observed at the concentrations studied. The results of the wound healing in vitro test showed that films containing 1.25% PPE are efficient in reducing the scratch open area, provoking almost total closure of the scratches within 48 h without cytotoxicity.
Assuntos
Antibacterianos/química , Bandagens , Membranas Artificiais , Álcool de Polivinil/química , Punica granatum/química , Amido/química , Animais , Linhagem Celular , Camundongos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/crescimento & desenvolvimentoRESUMO
Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm2, which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED50 = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE2 levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action.
Assuntos
Antiulcerosos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Modelos Animais de Doenças , Esterificação , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico/toxicidade , Indometacina/toxicidade , Camundongos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico/metabolismo , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND AND PURPOSE: Intestinal mucositis refers to mucosal damage caused by cancer treatment, and irinotecan is one of the agents most associated with this condition. Focusing on the development of alternatives to prevent this important adverse effect, we evaluated the activity of the flavonoid luteolin, which has never been tested for this purpose despite its biological potential. EXPERIMENTAL APPROACH: The effects of luteolin were examined on irinotecan-induced intestinal mucositis in mice. Clinical signs were evaluated. Moreover, histological, oxidative, and inflammatory parameters were analysed, as well as the possible interference of luteolin in the anti-tumour activity of irinotecan. KEY RESULTS: Luteolin (30 mg·kg-1 ; p.o. or i.p.) prevented irinotecan-induced intestinal damage by reducing weight loss and diarrhoea score and attenuating the shortening of the duodenum and colon. Histological analysis confirmed that luteolin (p.o.) prevented villous shortening, vacuolization, and apoptosis of cells and preserved mucin production in the duodenum and colon. Moreover, luteolin treatment mitigated irinotecan-induced oxidative stress, by reducing the levels of ROS and LOOH and augmenting endogenous antioxidants, and inflammation by decreasing MPO enzymic activity, TNF, IL-1ß, and IL-6 levels and increasing IL-4 and IL-10. Disruption of the tight junctions ZO-1 and occludin was also prevented by luteolin treatment. Importantly, luteolin did not interfere with the anti-tumour activity of irinotecan. CONCLUSION AND IMPLICATIONS: Luteolin prevents intestinal mucositis induced by irinotecan and therefore could be a potential adjunct in anti-tumour therapy to control this adverse effect, increasing treatment adherence and consequently the chances of cancer remission.
Assuntos
Mucosite , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Camptotecina/uso terapêutico , Camptotecina/toxicidade , Mucosa Intestinal , Irinotecano/uso terapêutico , Luteolina/farmacologia , Luteolina/uso terapêutico , Camundongos , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controleRESUMO
Green propolis is a resinous substance used in folk medicine given its anti-inflammatory, antibacterial, and anti-ulcer effects. Our research group has already confirmed the gastroprotective activity of hydroalcoholic extract from green propolis (HEGP), as well as of its main isolated compounds. In continuity, this study evaluated the antioxidant mode of action involved in the preventive effect induced by HEGP, and its therapeutic gastric healing potential on installed ulcers. In addition, the healing effect of its main compound Artepillin C was also investigated. Acute and chronic ulcers were induced in rats by given ethanol or acetic acid, respectively. In acute model, the rats were orally pre-treated with vehicle (water plus 1% Tween, 1 mL/kg), HEGP (30-300 mg/kg), or carbenoxolone (200 mg/kg) 1 h prior the ulcer induction. In the chronic ulcer protocol, the rats received vehicle (water plus 1% Tween, 1 mL/kg), HEGP (300 mg/kg), or omeprazole (20 mg/kg) twice a day by 7 days, whereas groups of mice received vehicle (water plus 1% Tween, 1 mL/kg), Artepillin C (18 mg/kg), or ranitidine (20 mg/kg) twice a day by 4 days. Ulcerated tissue was collected for histological, histochemical, immunostaining, oxidative, and inflammatory analyses. The in vitro scavenger activity of HEGP was also verified using the DPPH assay. The oral pre-treatment with HEGP (100 and 300 mg/kg) prevented the gastric epithelial damage promoted by ethanol. Besides, HEGP (100 and 300 mg/kg) reduced SOD activity about 11% and 26%, respectively, and increased the activity of GST around 20% and CAT in 80%. HEGP (300 mg/kg) also reduced the production of reactive oxygen species, as well as lipoperoxidation levels in the ethanol-ulcerated tissue. In the acetic acid-induced chronic ulcer, the daily treatment with HEGP (300 mg/kg) accelerates the healing process by 71%. In this model, HEGP normalized SOD and CAT activity and increased GST activity by 109% when compared to non-ulcerated rats. In both models, the extract administration increased the mucin PAS staining and reduced the myeloperoxidase activity at the ulcer site. Moreover, the treatment with HEGP enhanced the PCNA immunostaining, but did not alter the concentration of collagen in the acetic acid-ulcerated tissue. The extract had a direct DPPH radical-scavenging ability (LogIC50: 0.56). Besides, as expected, HPLC analysis showed Artepillin C as a major compound and its administration at 18 mg/kg also accelerated the gastric healing ulcer process in mice. Our findings confirm that HEGP displays both gastroprotective and gastric healing properties, contributing to the validation of its popular use as preventive and therapeutic approaches. These actions occur through the increase in mucin production and the reestablishment of the oxidative balance due to a reduction in gastric inflammation.
Assuntos
Antioxidantes/farmacologia , Fenilpropionatos/farmacologia , Extratos Vegetais/farmacologia , Própole/farmacologia , Substâncias Protetoras/farmacologia , Úlcera Gástrica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Antiulcerosos/farmacologia , Brasil , Catalase/metabolismo , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Masculino , Medicina Tradicional/métodos , Camundongos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/metabolismo , Superóxido Dismutase/metabolismoRESUMO
ETHNOPHARMACOLOGICAL IMPORTANCE: The species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is native to the Americas and is distributed widely throughout Brazil, where it is known as urtiga-brava, urtiga-vermelha, or urtigão. The leaves are often used as anti-inflammatory and antirheumatic agents and for the treatment of gastric disorders. However, the pharmacological mode of action underlying the gastroprotection induced by this species has not been investigated. AIM OF THE STUDY: To contribute to the knowledge of the gastroprotective mode of action of the hydroalcoholic extract of U. baccifera (HEU) leaves. MATERIALS AND METHODS: Antiulcerogenic effect of HEU against ethanol-induced acute gastric ulcer was evaluated in rats and mice at doses of 3-300 mg/kg. NO-synthase inhibitor (L-NAME), SH blocker (NEM), cyclooxygenase inhibitor (indomethacin) and alpha 2-adrenergic receptor antagonist yohimbine were used to evaluate the participation of cytoprotective factors in HEU gastroprotection. Moreover, the levels of reduced gluthatione (GSH) and cytokines (TNF, IL-6, IL4 and IL-10), as well as the enzymatic activity of gluthatione S-transferase (GST), myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) were measure. Moreover, the samples were analyzed histologically and the antisecretory capability of HEU were quantified using pylorus ligated rats. RESULTS: The phytochemical analysis of HEU (UPLC/ESI-IT-MS) identified the flavonoids diosmetin and apigenin glucuronide. Furthermore, HEU decreased the occurrence of ethanol-induced ulcers at 30 and 300 mg/kg by 57% and 66%, respectively, compared with the vehicle. The gastroprotective effects were accompanied by increased GSH levels and GST and SOD activity as well as by reduced MPO activity in vivo and in vitro, revealing antioxidant effects and inhibition of neutrophil infiltration. The beneficial effects of 30 and 300 mg/kg HEU were also observed upon histological analyses. Regarding the mode of action, the gastroprotective effect of HEU was abolished by the pre-administration of L-NAME, NEM, indomethacin or yohimbine. Moreover, HEU was able to decrease the IL-6, IL-4 and IL-10 in ulcerated tissue, as well as the pepsin activity of the gastric juice in pylorus-ligated rats. CONCLUSION: Together, the results confirmed that the gastroprotection elicited by HEU was due reduction in oxidative damage, neutrophil migration, and peptic activity. This work validates the popular use of U. baccifera to treat gastric disorders and supports important future research for the identification of gastroprotective molecules from this species.
Assuntos
Antiulcerosos/farmacologia , Extratos Vegetais/farmacologia , Úlcera Gástrica/prevenção & controle , Urticaceae/química , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/isolamento & purificação , Antioxidantes/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Folhas de Planta , Ratos , Ratos WistarRESUMO
OBJECTIVES: This study aimed to investigate the diuretic efficacy of myricetin-3-O-α-rhamnoside (myricitrin), a common naturally occurring plant-derived flavonoid, obtained from Marlierea eugeniopsoides (D.Legrand & Kausel) D.Legrand leaves in rats. METHODS: For that, female Wistar rats were treated by oral route with the different treatments and kept in metaboloic cages for 8-h or 24-h experiment. The volume and urinary parameters were measured at the end of the period and compared between groups. KEY FINDINGS: When orally given to rats and compared to the vehicle-treated group, myricitrin (0.3 and 1 mg/kg) was able to stimulate rat diuresis, natriuresis and kaliuresis. The combination myricitrin plus hydrochlorothiazide, but not plus furosemide or amiloride, potentiated the urinary volume when compared to the effects of drugs alone. Besides, the 8-h renal effects of myricitrin were prevented in the presence of a cyclooxygenase inhibitor and a muscarinic receptor antagonist. However, all groups treated with myricitrin showed a significant reduction in Cl- excretion. In addition, a reduction in the urinary excretion of Cl- and HCO 3 - was detected on 24-h analysis, a result that showed to be associated with an increase of these anions in the blood samples from the myricitrin-treated group. Despite these alterations, no changes in urinary or blood pH were detected. CONCLUSIONS: Taking together, although the results of this study point to the diuretic potential of myricitrin, the reduction in urinary Cl- and HCO 3 - excretion should be considered in future approaches, as well as for therapeutic applicability.
Assuntos
Diuréticos/farmacologia , Flavonoides/farmacologia , Myrtaceae/química , Animais , Diurese/efeitos dos fármacos , Diuréticos/administração & dosagem , Diuréticos/isolamento & purificação , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Flavonoides/administração & dosagem , Flavonoides/isolamento & purificação , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/farmacologia , Natriurese/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
BACKGROUND: Considering the therapeutic potential of phenolic compounds, the purpose of the present study was to investigate the mechanisms involved in the relaxation induced by cryptostrobin and catechin, isolated from Eugenia mattosii D. Legrand leaves, in the aorta of spontaneously hypertensive rats (SHR). METHODS: The thoracic aorta was isolated from SHR and kept in the organ bath system by recording contractile or relaxant responses. RESULTS: The addition of cumulative concentrations of cryptostrobin and catechin induced endothelium-dependent and-independent relaxation in aorta rings from SHR, as well as both compounds were effective in reducing phenylephrine-induced contraction. Pretreatment of aortic rings with Nω-nitro-l-arginine methylester (L-NAME, an inhibitor of nitric oxide synthase) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor of soluble guanylate cyclase), resulted in a significant change of relaxant effect induced by catechin, and a slight influence on cryptostrobin-induced relaxation. Muscarinic receptor and potassium channels are involved in catechin-induced relaxation as assessed using atropine (a muscarinic receptor antagonist), tetraethylammonium (a non-selective K+ channel blocker) and glibenclamide (an ATP-sensitive K+ channel blocker). Conversely, cryptostrobin, but not catechin, blunted the contraction induced by the addition of phenylephrine in a calcium-free solution. Besides that, cryptostrobin attenuated the contraction of rat aorta rings induced by internal Ca2+ release and external Ca2+ influx. CONCLUSIONS: These findings indicated that cryptostrobin and catechin alter vascular smooth muscle reactivity, and this effect may be involved, at least in part, by enhancing the endothelium NO/cGMP pathway and potassium channels activation. In addition, cryptostrobin reduced the phenylephrine, KCl and CaCl2-induced contractions in a calcium-free solution.
Assuntos
Aorta Torácica/efeitos dos fármacos , Catequina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Eugenia/química , Hipertensão/fisiopatologia , Polifenóis/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta Torácica/fisiopatologia , Catequina/isolamento & purificação , Endotélio Vascular/fisiopatologia , Técnicas In Vitro , Masculino , Folhas de Planta/química , Polifenóis/isolamento & purificação , Ratos Endogâmicos SHR , Vasodilatadores/isolamento & purificaçãoRESUMO
Salvia lachnostachys is an herbaceous plant with anti-inflammatory, analgesic and cytotoxic properties. This study investigated the antitumor effect of an ethanolic extract of Salvia lachnostachys leaves (EES) in a solid Ehrlich carcinoma model. Ehrlich cells were inoculated subcutaneously in the right pelvic member (2 × 106 cells) in female Swiss mice. The animals were treated with vehicle (10 mL kg-1, p.o.), EES (30 and 100 mg kg-1, p.o.), or methotrexate (2.5 mg kg-1, i.p.) for 21 days (early treatment) or 14 days (late treatment) after tumor inoculation, or 10 days before tumor inoculation and continued for 21 days after tumor inoculation (chemopreventive treatment). The acute toxicity test was performed according OECD guidelines Late treatment with EES had no antitumor effect. Early treatment with 100 mg kg-1 EES prevented tumor development, increased tumor necrosis factor-α (TNF-α) levels and decreased tumor superoxide dismutase (SOD) activity, interleukin-10 (IL-10) levels and Cyclin D1 expression, and tumor cell necrosis was observed. Chemopreventive treatment with EES for 10 and 31 days prevented tumor development in the same manner. EES treatment for 31 days decreased hepatic and tumor SOD activity, tumor IL-10 levels and Cyclin D1 expression, and increased tumor reduced glutathione, N-acetylglucosaminidase, reactive oxygen species, lipid peroxidation, TNF-α levels and Nrf2 expression. No toxicity was observed in the acute toxicity assay. In conclusion, EES had an antitumor effect by inhibiting Cyclin D1 expression and increasing inflammation with early and chemopreventive treatment. Modulation of the antioxidant system also contribute for the antitumor effects of EES.
Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Salvia/química , Animais , Anticarcinógenos/química , Antineoplásicos Fitogênicos/química , Carcinoma de Ehrlich/genética , Carcinoma de Ehrlich/metabolismo , Quimioprevenção , Cromatografia Líquida de Alta Pressão , Ciclina D1/genética , Ciclina D1/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Camundongos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
The flavonoid hesperidin is abundantly found in citrus fruits and is used to treat vascular diseases. Previous studies described its gastroprotective actions against stress or ethanol-induced ulcer in rodents; however, results from indomethacin-induced ulcer were controversy. Therefore, given its clinical use and contradictory findings in acute models, this study aims to evaluate the effect of hesperidin (1-10â¯mg/kg, p.o) on chronic gastric ulcer induced by acetic acid in rats, a model that resembles the ulcer in humans. Moreover, the effects of hesperidin on mucin levels and on inflammatory and oxidative parameters at ulcer site were also measured. The treatment with hesperidin at 3 and 10â¯mg/kg, once a day, by seven days, accelerated by 34 and 62%, respectively, the ulcer healing process when compared to vehicle-treated group (99.1⯱â¯6.4â¯mm2). Histological and histochemistry analyses confirmed the healing effect with significant favoring of mucin production. Hesperidin also promoted the preservation of reduced glutathione levels in the gastric mucosa tissue, as well as the normalization of superoxide dismutase and catalase activities at similar levels to those found in the non-ulcerated group. In addition, flavonoid administration increased the enzymatic activity of glutathione-S-transferase by 35%. Tissue lipoperoxides and myeloperoxidase activity were reduced after hesperidin treatment. In conclusion, the flavonoid hesperidin revealed a gastric healing activity in the ulcerated mucosa, an effect that showed to be associated with the reduction of oxidative damage at ulcer site, due to the reduction of the neutrophil migration and the strengthening of the mucus barrier next to the mucosa.
Assuntos
Glicosídeos/uso terapêutico , Hesperidina/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Ácido Acético/toxicidade , Animais , Catalase/metabolismo , Esquema de Medicação , Flavanonas/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Glicosídeos/farmacologia , Hesperidina/farmacologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
Baccharis dracunculifolia is a medicinal plant native to southeastern Brazil and is the main botanical source used by bees (Apis mellifera) in the manufacture of green propolis and display similar gastroprotective action and chemical profile. This article reports the healing gastric ulcer activity of the hydroethanolic extract of B. dracunculifolia (HEBD) in an acetic acid-induced ulcer model. In addition to the extract, the isolated compounds ferulic acid, p-coumaric acid, caffeic acid, baccharin, and aromadendrin-4'-O-methyl ether were also assayed. HEBD at a dose of 300 mg/kg reduced the ulcerated area by 49.4% after treatment for 7 days, twice a day. Histological analyses revealed that the margins and base of the ulcer obtained significant regeneration, and periodic acid Schiff base staining showed a 78.2% increase in the mucin levels. The action on the enzymatic antioxidant system demonstrated an increased activity of superoxide dismutase and glutathione-S-transferase, in addition to raising glutathione reduced levels and myeloperoxidase activity. HEBD did not show cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazole bromine test. In vitro, HEBD inhibited the H+ /K+ -ATPase enzyme and showed antioxidant activity in the 2,2 diphenyl-1-picryllydrazyl test. Regarding the isolated compounds, oral administration of p-coumaric acid (15 mg/kg) reduced the ulcerated area by 66.2%. The results suggest that HEBD recovers the gastric ulcerated tissue, raising mucus and antioxidant enzyme levels, and reducing the H+ /K+ -ATPase activity. In addition, the findings confirm that p-coumaric acid is a pivotal bioactive compound on the gastric healing effects elicited by HEBD. © 2019 BioFactors, 45(3):479-489, 2019.
Assuntos
Baccharis/química , Extratos Vegetais/uso terapêutico , Propionatos/metabolismo , Úlcera Gástrica/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Ácidos Cumáricos , Glutationa/metabolismo , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Úlcera Gástrica/metabolismo , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Plants and their parts are a part of life in many Brazilian communities, as observed in the jackfruit. The jackfruit seeds are consumed, usually, as roasted, boiled, steamed, and are eaten as a snack. OBJECTIVE: The present study was carried out to identify the Artocarpus heterophyllus seeds toxicity and cytotoxic activity. METHODS: The extracts were tested in toxicity assays like, brine shrimp lethality assay, hemolysis assay, and effect of seed extracts on T47D, TH29 and B16F10 cancer cell lines, and in acute and subchronic toxicity in mice. RESULTS: Artocarpus heterophyllus seed presents no toxic effects in brine shrimp, no hemolytic activity, and was effective in cancer cell lines like T47D, TH29 and B16F10. IC50 obtained from extracts was 46.67⯵g/ml of chloroform extract in T47D cells, 23.42⯵g/ml of ethanolic extract in HT29 cells, and 74.31⯵g/ml of ethyl acetic extract in B16F10 cells. Ethanolic extract presented zero lethality index and was able to reduce the level of glycemia in females (32.3%) in the subchronic test. CONCLUSIONS: With this results we can conclude that Artocarpus heterophyllus seeds presents no toxicity, and is very effective in determinated cancer cell lines, requiring further studies to validate their use as active natural product against cancer cells.
RESUMO
The gastroprotective potential of the methanolic extracts from peels (MEPe), seeds (MESe) and pulp (MEPu) of Chrysophyllum cainito L. (Sapotaceae) fruits was evaluated in mice using ethanol/HCl- and indomethacin-induced ulcer, as well as the antiulcer effect of the juice and flour from this fruit. The lowest oral gastroprotective dose of MEPe, MESe and MEPu against ethanol/HCl was 3, 3 and 10 mg/kg, respectively. Moreover, all extracts increased mucin secretion at 176, 198 and 193%. Intraperitoneal administration of MEPe (0.3 mg/kg), MESe (0.3 mg/kg) and MEPu (1 mg/kg) also promoted gastroprotection against ethanol/HCl. In addition, MEPe (3 mg/kg, p.o), MESe (3 mg/kg, p.o) and MEPu (10 mg/kg, p.o) reduced indomethacin-induced gastric ulcer in mice by 78, 70 and 50%, respectively. Regarding the mode of action, the gastroprotective effect of MEPe was decreased by the pre-administration of N-ethylmaleimide (NEM, a sulfhydryl group chelator, 10 mg/kg, i.p), glibenclamide (a potassium channel blocker, 10 mg/kg, i.p), yohimbine (10 mg/kg, i.p, an alpha-adrenergic receptor antagonist, 10 mg/kg, i.p) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p). The gastroprotective effect of MESe was reduced by the pre-administration of NEM, glibenclamide, N-Nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 70 mg/kg, i.p) and yohimbine, while MEPu had the gastroprotective effect decreased in animals pretreated with NEM and L-NAME. However, the extracts did not reduce gastric acid secretion. The supplementation with the flour from C. cainito fruit at 10% by 7 days, but not the juice intake, displayed gastroprotective potential, evidencing the fruit as a promising functional food. Together, the antiulcer effect of extracts of the C. cainito fruit in different experimental models was confirmed by the favoring of mucosal protective mechanisms among different, but complementary, modes of action. In parallel, the gastroprotective effects of the flour from C. cainito fruit were also described.
Assuntos
Antiulcerosos/farmacologia , Frutas/química , Mucosa Gástrica/efeitos dos fármacos , Sapotaceae/química , Úlcera Gástrica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Etanol/química , Feminino , Indometacina/farmacologia , Camundongos , NG-Nitroarginina Metil Éster/farmacologia , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Folhas de Planta/químicaRESUMO
AIM: To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia (HEEP) leaves on gastric ulcer healing. METHODS: In this rat study involving males, intact (cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity. RESULTS: Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males (52.44%), intact females (85.22%), and ovariectomized females (65.47%), confirming that HEEP accelerates the healing of acetic acid-induced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor (intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2 (intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed. CONCLUSION: In gastric ulcers, HEEP-induced healing (modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.