RESUMO
Low-level laser therapy (LLLT) in acupuncture is a low-power laser applied to acupoints for providing luminous energy, capable to produce photobiological induction that results in biochemical, bioelectric, and bioenergetic effects. ST36 (Zusanli) is a point of acupuncture commonly used for treatment of several pathological alterations, such as inflammation, acute pain, and gastrointestinal disorders. In this study, we evaluated the anti-inflammatory effect of LLLT (830 nm, 4 J/cm(2)) in ST36 acupoint through the model of carrageenan-induced paw edema in mice and the possible mechanisms involved. Female Swiss mice were treated with LLLT in ST36 before the paw edema induction, which was measured by means of a digital micrometer and the temperature through a high-resolution digital thermograph. After this, the levels of reactive oxygen species (ROS), lipid hydroperoxides (LOOH), and reduced glutathione (GSH) were quantified. In another set of experiments, the paw edema was induced by bradykinin, histamine, and prostaglandin E2 (PGE2). LLLT in ST36 acupoint significantly inhibited the edema formation for 4 h after the carrageenan injection and reduced the paw temperature in 10 %. Furthermore, LLLT also reduced the levels of ROS (55 %) and LOOH (50 %) but, however, did not alter the GSH levels. LLLT in ST36 reduced the paw edema induced by bradykinin (30 min, 6 %, 60 min, 7 %), histamine (30 min, 11 %), and PGE2 (90 min, 10 %, 120 min, 16 %). In conclusion, these results prove that LLLT in ST36 acupoint produces a relevant anti-inflammatory effect, reducing edema, temperature, and free radicals levels in mice paw.
Assuntos
Pontos de Acupuntura , Edema/terapia , Terapia com Luz de Baixa Intensidade , Animais , Bradicinina/metabolismo , Carragenina/efeitos adversos , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Glutationa/metabolismo , Histamina/metabolismo , Inflamação/terapia , Peróxidos Lipídicos/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipê-roxo' and has been used in folk medicine as anti-inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases.
Assuntos
Antiulcerosos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Fitoterapia , Casca de Planta/química , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Tabebuia/química , Ácido Acético , Animais , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Muco/efeitos dos fármacos , Fenóis/análise , Fenóis/uso terapêutico , Extratos Vegetais/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Cicatrização/efeitos dos fármacosRESUMO
In this study, we determined the anti-inflammatory effect of manual acupuncture at the Sanyinjiao or Spleen 6 (SP6) point on carrageenan-induced peritonitis in mice and investigated mechanisms that may underlie this effect. In the first set of experiments, male Swiss mice were allocated into five groups: the control (sterile saline), dexamethasone (DEXA), invasive sham-acupuncture (non-acupoint), SP6 acupuncture and carrageenan-treated groups. Ten minutes after needle retention or 30 min after DEXA treatment, mice received an intraperitoneal injection of carrageenan (750 µg/mouse). After 4 h, total leukocyte and differential cell counts (neutrophils and mononuclear), myeloperoxidase (MPO) activity, vascular permeability and cytokine levels were evaluated. In another set of experiments, adrenalectomized (ADX) mice were used to study the involvement of the adrenal gland on the therapeutic effects of acupuncture. Mice were allocated into two groups: the ADX and sham-operated animals (Sham ADX) that were subdivided into four subgroups each: the control (sterile saline), DEXA, SP6 acupuncture and carrageenan-treated groups. The SP6 and DEXA treatments inhibited the inflammatory cell infiltration, vascular permeability and MPO activity in carrageenan-injected mice. In addition, the SP6 treatment also increased interleukin (IL)-10 levels. In contrast, when the animals were adrenalectomized, the SP6 treatment failed to reduce total leukocyte and the plasma extravasation. In conclusion, this study clearly demonstrates the anti-inflammatory effect of SP6 acupuncture in a model of carrageenan-induced peritonitis. Our results demonstrated that SP6 acupuncture depends of the adrenal glands and increased IL-10 levels to produce its anti-inflammatory action.
RESUMO
Tabebuia avellanedae is commonly used for the treatment of peptic ulcers. We carried out this study with the ethanolic extract of bark from Tabebuia avellanedae (EET) (30-1000 mg/kg) to determine its gastroprotective activity and to clarify the pathways involved in this effect. Acute gastric ulceration in rats was produced by oral administration of ethanol and ibuprofen. After ethanol administration, the gastric wall mucus was examined. Chronic gastric ulceration was produced by injection of acetic acid in rat gastric subserosa. Anti-secretory studies were undertaken using Shay rat pylorus ligature technique and measurement of enzymatic activity of H+, K+-ATPase in vitro. Administration of EET p.o. or i.p. significantly inhibited gastric mucosa damage induced by ethanol and ibuprofen. The anti-ulcer effect was further confirmed by enhanced gastric mucus production. In pylorus ligature rats, EET significantly reduced the basal gastric acid secretion and total acidity; moreover, it inhibited the increase in total acidity induced by histamine. In addition, EET reduced the activity of H+, K+, ATPase. The results obtained in the present pharmacological assay indicate that this plant has a protective action against gastric lesions, involving the maintenance of protective factors, such as mucus and prostaglandin, besides the reduction of gastric total acidity.
Assuntos
Antiulcerosos/farmacologia , Extratos Vegetais/farmacologia , Tabebuia , Animais , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Ibuprofeno/toxicidade , Camundongos , Fitoterapia , Casca de Planta/química , Ratos , Ratos Wistar , Úlcera Gástrica/tratamento farmacológicoRESUMO
Natural polysaccharides have emerged as an important class of bioactive compounds due their beneficial biological effects. Here we investigated the protective and healing effects of rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen leaves in an experimental model of intestinal inflammation in mice and in heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2). The findings demonstrated that RGal treatment for 7 days reduced the severity of DSS-induced colitis by protecting mice from weight loss, macroscopic damage and reduction of colon length. When compared to the DSS group, RGal also protected the colon epithelium and promoted the maintenance of mucosal enterocytes and mucus secreting goblet cells, in addition to conserving collagen homeostasis and increasing cell proliferation. In an in vitro barrier function assay, RGal reduced the cellular permeability after exposure to IL-1ß, while decreasing IL-8 secretion and claudin-1 expression and preserving the distribution of occludin. Furthermore, we also observed that RGal accelerated the wound healing in Caco-2 epithelial cell line. In conclusion, RGal ameliorates intestinal barrier function in vivo and in vitro and may represent an attractive and promising molecule for the therapeutic management of ulcerative colitis.
Assuntos
Colite/patologia , Sulfato de Dextrana , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Polissacarídeos/farmacologia , Animais , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Feminino , Fibrose , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Mucosa Intestinal/metabolismo , Camundongos , Proteínas de Junções Íntimas/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
The possible gastroprotective effects of the hydroalcoholic extract of Polygala paniculata in rats have been evaluated. We have investigated the effects of this hydroalcoholic extract on acute lesions induced by ethanol (70%, p.o.) and indomethacin (20 mg kg(-1), s.c.). Its influence on mucus secretion was investigated, measured as the amount of Alcian blue dye estimated by colorimetry, and antisecretory effects were assessed in the pylorus ligature model. The treatment of rats with a crude hydroalcoholic extract of P. paniculata (HEPP; 30, 100, 300 mg kg(-1), p.o., or 3, 10 and 30 mg kg(-1), i.p.) decreased the ulcer index, and maintained the gastric mucus production in acute gastric lesions caused by ethanol 70%. In addition, the extract partially protected the mucosa against indomethacin-induced lesions. The extract did not change the volume and acidity of gastric secretion in the pylorus-ligated rat. An additional antioxidant activity of the extract and its isolated flavonoid compound rutin, in the DPPH free radical scavenging assay, was observed. In conclusion, HEPP exhibited marked gastroprotection; these effects may have involved prostaglandins and be related to cytoprotective factors, such as antioxidant activity and maintenance of mucus production.
Assuntos
Antiulcerosos/farmacologia , Extratos Vegetais/química , Polygala/química , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Brasil , Colorimetria , Relação Dose-Resposta a Droga , Etanol , Feminino , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Suco Gástrico/efeitos dos fármacos , Suco Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Indometacina , Ligadura , Medicina Tradicional , Piloro , Ratos , Ratos Wistar , Rutina/isolamento & purificação , Rutina/farmacologia , Úlcera Gástrica/induzido quimicamenteRESUMO
Mikania laevigata (Asteraceae) is a native plant from South America and popularly used as antispasmodic and to treat respiratory diseases. Coumarin is the major chemical substance found in this plant, which have been shown to have antifertility activity in female rats. This study evaluates the toxicity of the exposure to the Mikania laevigata syrup using coumarin as chemical marker on reproductive endpoints in male Wistar rats. Endpoints including reproductive organs weight, sperm and spermatids numbers and sperm morphology were evaluated. Animals were treated daily with Mikania laevigata syrup (3.5; 7.0 and 14.0mg/kg of coumarin) during 90 days by oral gavage. No alterations were observed in body and organ weights, sperm and spermatids numbers as well as sperm morphology of the male rats after the exposure to the Mikania laevigata syrup. Results therefore suggest absence of male reproductive toxicity of the Mikania laevigata syrup at tested doses.
Assuntos
Fertilidade/efeitos dos fármacos , Genitália Masculina/efeitos dos fármacos , Mikania , Parassimpatolíticos/farmacologia , Medicamentos para o Sistema Respiratório/farmacologia , Espermatozoides/efeitos dos fármacos , Administração Oral , Animais , Brasil , Cumarínicos/análise , Relação Dose-Resposta a Droga , Epididimo/efeitos dos fármacos , Intubação Gastrointestinal , Masculino , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/química , Parassimpatolíticos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Ratos , Ratos Wistar , Medicamentos para o Sistema Respiratório/administração & dosagem , Medicamentos para o Sistema Respiratório/química , Medicamentos para o Sistema Respiratório/toxicidade , Glândulas Seminais/efeitos dos fármacos , Contagem de Espermatozoides , Espermatogênese/efeitos dos fármacos , Testículo/efeitos dos fármacos , Fatores de TempoRESUMO
Maytenus ilicifolia Mart. ex. Reissek (Celastraceae), a medicinal plant known in Brazil as "espinheira-santa" is commonly used to treat gastric disorders. The effect of the flavonoid-rich fraction separated from the leaves was evaluated for its gastroprotective properties and the mechanism(s) involved in this activity. Intraperitoneal administration of the flavonoid-rich fraction potently protected rats from experimentally induced chronic (ED(50)=79 mg/kg) and acute gastric lesions by ethanol (ED(50)=25mg/kg) and indomethacin (ED(50)=4 mg/kg) without altering the decreased amount of cytoprotective glutathione and mucus amount in the injured gastric mucosa. A potent reduction of gastric acid hypersecretion (ED(50)=7 mg/kg, i.p.) was accompanied by a reduction of nitric oxide release (ED(50)=1.6 mg/kg, i.p.) in the gastric secretion of 2h pylorus ligated rats which suggests an important role for nitric oxide-dependent mechanisms. Inhibition of gastric acid secretion in vivo was correlated with the in vitro inhibition of rabbit gastric H(+),K(+)-ATPase activity (IC(50)=41 microg/mL). Chemical investigation of the fraction showed galactitol (25%), epicatechin (3.1%) and catechin (2%) as the majoritary components. Collectively, the results show that the flavonoid-rich fraction of Maytenus ilicifolia potently protects animals from gastric lesions with high potency through inhibition of gastric acid secretion.
Assuntos
Flavonoides/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Maytenus/química , Substâncias Protetoras/uso terapêutico , Inibidores da Bomba de Prótons , Úlcera Gástrica/tratamento farmacológico , Ácido Acético , Animais , Feminino , Ácido Gástrico/metabolismo , Suco Gástrico/química , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Indometacina , Muco/metabolismo , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Folhas de Planta/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismoRESUMO
Mikania laevigata, popularly known in Brazil as "guaco", is largely used in folk medicine against respiratory diseases. However, neither the assessment of the toxicity of "guaco" syrup (GS, used by humans) nor its efficacy or mechanisms of action has been properly investigated. Using in vitro procedures, we showed that the hydroalcoholic extract (HE) from Mikania laevigata induces a concentration-dependent relaxation of rat trachea which does not depend on epithelium-derived substances but involves changes in the cellular mobilization of calcium, perhaps due to a direct effect on membrane potassium channels. In addition, we assessed both oral and intraperitoneal acute toxicity, as well as the oral subchronic and chronic toxicity of GS containing controlled amounts of coumarin, the main biological marker of Mikania laevigata preparations used in humans. The calculated LD(50) of GS after intraperitoneal administration was 0.904 g/kg in mice (both sexes) and 0.967 and 0.548 g/kg in male and female rats, respectively. However, the LD(50) values of GS by the oral route were calculated to be up to 10 g/kg, in both male and female mice and rats. Repeated dose 28- or 90-day oral treatment with GS (75, 150 and 300 mg/kg) did not produce any disturbances in the hematological or biochemical parameters of either male or female rats, nor did it provide evidence of toxicity in the hepatic, renal or pancreatic systems. Besides the mechanistic findings, our results provide evidence of the safety of Mikania laevigata in rodents, even after subchronic and chronic administration, at least in relation to the evaluated parameters.
Assuntos
Mikania/química , Relaxamento Muscular/efeitos dos fármacos , Extratos Vegetais/farmacologia , Traqueia/efeitos dos fármacos , 4-Aminopiridina/farmacologia , Acetilcolina/farmacologia , Animais , Brasil , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glibureto/farmacologia , Técnicas In Vitro , Masculino , Camundongos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Oxidiazóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Bloqueadores dos Canais de Potássio/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Wistar , Tetraetilamônio/farmacologia , Testes de Toxicidade Aguda/métodos , Testes de Toxicidade Crônica/métodos , Traqueia/fisiologiaRESUMO
Achillea millefolium L. (Asteraceae), popularly known as yarrow, has been used in folk medicine to treat complaints such as inflammation, pain, wounds, hemorrhages and gastrointestinal disturbances. The aim of the present study was to assess the safety and efficacy of the aqueous extract (AE) of the plant after chronic exposure. Indeed, the AE was effective in protecting the gastric mucosa against acute gastric lesions induced by ethanol and indomethacin and in healing chronic gastric lesions induced by acetic acid with (ED(50)=32 mg/kg, p.o.). Safety studies were performed in female and male Wistar rats treated daily with AE (0.3-1.2 g/kg, p.o./day) or vehicle (water, 10 ml/kg/day) for 28 or 90 consecutive days. Satellite groups consisted of animals sacrificed 30 days after the end of these treatments. Clinical observations, body and organ weight measurements, gross autopsy, hematology, clinical biochemical and histopathological examinations were performed. Slight changes in liver weight, cholesterol, HDL-cholesterol and glucose were observed in male and female animals. These changes were not correlated with dose or time of exposure of the animals to the AE. Overall, the results show the antiulcer potential of the aerial parts of the Achillea millefolium which is accompanied by no signs of relevant toxicity even at very long chronic exposure.
Assuntos
Achillea/química , Antiulcerosos , Úlcera Gástrica/tratamento farmacológico , Administração Oral , Animais , Antiulcerosos/efeitos adversos , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Contagem de Células Sanguíneas , Coagulação Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Medicinal plants are commonly used in Latin American folk medicine for the treatment of gastric problems. In order to understand the properties of some of their chemical constituents, four natural xanthones, an acetylated derivative, two coumarins (mammea A/BA and mammea C/OA) isolated from Calophyllum brasiliense Cambess and two flavonoids (minimiflorin and mundulin) isolated from Lonchocarpus oaxacensis Pittier, and the chalcone lonchocarpin isolated from Lonchocarpus guatemalensis Benth were tested for their activities on gastric H+,K+-ATPase isolated from dog stomach. All the compounds tested inhibited H+,K+-ATPase activity with varied potency. The xanthones inhibited the H+,K+-ATPase with IC50 values ranging from 47 microM to 1.6 mM. Coumarins inhibited H+,K+-ATPase with IC50 values of 110 and 638 microM. IC50 values for the flavonoids ranged from 9.6 to 510 microM among which minimiflorin was the most potent. The results suggest that H+,K+-ATPase is sensitive to inhibition by several types of structurally different natural compounds. The potency of the effects on gastric H+,K+-ATPase depends on the presence, position and number of hydroxyls groups in the molecule. Collectively, these results suggest a potential for important pharmacological and toxicological interactions by these types of natural products at the level of H+,K+-ATPase which may explain, at least in part, the gastroprotective properties, indicated by traditional medicine, of the plants from which these compounds were isolated.
Assuntos
Cumarínicos/farmacologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Plantas Medicinais/química , Inibidores da Bomba de Prótons , Estômago/enzimologia , Xantonas/farmacologia , Animais , Calophyllum/química , Cumarínicos/isolamento & purificação , Derris/química , Cães , Inibidores Enzimáticos/isolamento & purificação , Feminino , Flavonoides/isolamento & purificação , Xantonas/isolamento & purificaçãoRESUMO
We determined the effects of subchronic exposure to aqueous extract of leaves from Achillea millefolium (AE) on enzyme- and non-enzyme-dependent antioxidant systems in rats. Seven days treatment with AE (1 g/kg/twice a day, p.o.) altered the reduced glutathione (GSH) levels and antioxidant enzyme activities in several organs of the animals. Amount of GSH in uterus was increased (73%) while in kidneys it was decreased (23%). Besides, NAD(P)H quinone oxidoreductase 1 (NQO1) activity was increased in forestomach (26%) and in liver (64%), while glutathione S-transferase activity was decreased in the forestomach (32%) and increased in the liver (41%), kidney (35%) and uterus (37%). In preliminary experiments targeting the interaction of AE with acetaminophen (600 mg/kg, p.o.), we observed augmentation of acetaminophen-induced increase of the plasmatic alanine aminotransaminase, aspartate aminotransaminase and lactate dehydrogenase. Overall, the results indicate a potential toxic interaction of AE compounds with xenobiotics that use the glutathione pathway.
Assuntos
Achillea/química , Antioxidantes/metabolismo , Extratos Vegetais/farmacologia , Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Animais , Feminino , Glutationa/metabolismo , Rim/enzimologia , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Extratos Vegetais/toxicidade , Folhas de Planta/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Útero/metabolismoRESUMO
Green tea is an infusion of unfermented leaves of Camellia sinensis (L.) Kuntze (Theaceae), traditionally used for the treatment of obesity, hypercholesterolemia, and gastric complaints. This study evaluated the mechanisms involved in the gastric ulcer healing of the hydroalcoholic extract from green tea (GEt), its ethyl acetate fraction, (GEAc) and epigallocatechin gallate (EGCG) using the model of acetic acid-induced gastric ulcer in rats. The chronic gastric ulcer was induced by application of 80 % acetic acid on serosal mucosa of rats. After 7 days of oral treatment with GEt and GEAc, the ulcer area, mucin content, inflammatory parameters (MPO and NAG), and antioxidant system (GSH and LOOH levels, SOD and GST activities) were evaluated. In vitro, the scavenging activity of GEt and GEAc were also measured. The antisecretory action was studied on the pylorus ligature method in rats. Oral treatment with GEt and GEAc reduced significantly the gastric ulcer area induced by acetic acid. The gastric ulcer healing was accompanied by increasing of mucin content, restoration of GSH levels and SOD activity, and reduction of MPO and LOOH levels. In addition, GEt and GEAc reduced the DPPH free radicals in vitro. Furthermore, the oral treatment of animals with GEt and GEAc did not alter the gastric acid secretion or cause signs of toxicity. Collectively, these results showed that GEt had a pronounced antiulcer effect, possibly through maintenance of mucin content and reduction of inflammation and oxidative stress. In addition, the compounds present in its ethyl acetate fraction could be responsible for the extract activity.
Assuntos
Antiulcerosos/uso terapêutico , Camellia sinensis , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Acetatos/química , Ácido Acético , Animais , Antiulcerosos/farmacologia , Etanol/química , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Mucinas/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Ratos Wistar , Solventes/química , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Água/químicaRESUMO
The pathophysiology associated with increased prevalence of depression in diabetics is not completely understood, although studies have pointed the endocannabinoid system as a possible target. Then, we aimed to investigate the role of this system in the pathophysiology of depression associated with diabetes. For this, diabetic (DBT) male Wistar rats were intraperitoneally treated with cannabinoid CB1 (AM251, 1mg/kg) or CB2 (AM630, 1mg/kg) receptor antagonists followed by anandamide (AEA, 0.005mg/kg) and then submitted to the forced swimming test (FST). Oxidative stress parameters, CB1 receptor expression and serotonin (5-HT) and noradrenaline levels in the hippocampus (HIP) and prefrontal cortex (PFC) were also performed. It was observed that DBT animals presented a more pronounced depressive-like behavior and increase of CB1 receptor expression in the HIP. AEA treatment induced a significant improvement in the depressive-like behavior, which was reversed by the CB1 antagonist AM251, without affecting the hyperglycemia or weight gain. AEA was also able to restore the elevated CB1 expression and also to elevate the reduced level of 5-HT in the HIP from DBT animals. In addition, AEA restored the elevated noradrenaline levels in the PFC and induced a neuroprotective effect by restoring the decreased reduced glutathione and increased lipid hydroperoxides levels along with the decreased superoxide dismutase activity observed in HIP or PFC. Together, our data suggest that in depression associated with diabetes, the endocannabinoid anandamide has a potential to induce neuroadaptative changes able to improve the depressive-like response by its action as a CB1 receptor agonist.
Assuntos
Ácidos Araquidônicos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Depressão/tratamento farmacológico , Depressão/etiologia , Diabetes Mellitus Experimental/psicologia , Endocanabinoides/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Alcamidas Poli-Insaturadas/uso terapêutico , Receptor CB1 de Canabinoide/efeitos dos fármacos , Animais , Indóis/farmacologia , Masculino , Norepinefrina/metabolismo , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/biossíntese , Serotonina/metabolismo , Natação/psicologiaRESUMO
A structural characterization of polysaccharides obtained by aqueous extraction of ripe pulp of the edible exotic tropical fruit named tamarillo (Solanum betaceum) was carried out. After fractionation by freeze-thaw and α-amylase treatments, a fraction containing a mixture of highly-methoxylated homogalacturonan and of arabinogalactan was obtained. A degree of methylesterification (DE) of 71% and a degree of acetylation (DA) of 1.3% was determined by (1)H NMR spectroscopy and spectrophotometric quantification, respectively. A type I arabinogalactan was purified via Fehling precipitation and ultrafiltration through 50 kDa (cut-off) membrane. Its chemical structure was performed by sugar composition, HPSEC, methylation, carboxy-reduction and (13)C NMR spectroscopy analysis. Intraperitoneal administration of the arabinogalactan did not reduce the nociception induced by intraplantar injection of 2.5% formalin in mice, but significantly reduced the number of abdominal constrictions induced by 0.6% acetic acid, indicating that fraction has an antinociceptive effect on the visceral inflammatory pain model.
Assuntos
Analgésicos , Frutas/química , Galactanos , Dor/tratamento farmacológico , Solanum , Ácido Acético , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/uso terapêutico , Animais , Feminino , Formaldeído , Galactanos/química , Galactanos/isolamento & purificação , Galactanos/uso terapêutico , Metilação , Camundongos , Estrutura Molecular , Peso Molecular , Monossacarídeos/análise , Dor/induzido quimicamente , FitoterapiaRESUMO
The plants belonging to Pfaffia genus are used in folk medicine to treat gastric disturbances. This study examined the effects of an aqueous extract of Pfaffia glomerata (Spreng) Pedersen (AEP) on the gastrointestinal tract. Wistar rats were pretreated orally (p.o.) with the AEP (125, 250, 500 and 1000 mg.kg(-1)) before induction of ulcers by hypothermic restraint stress (HRS, 3 h restraint stress at 4 degrees C), ethanol (ET, 70%; 0.5 ml/animal; p.o.) or indomethacin (IND, 20 mg.kg(-1); s.c.). Control animals received water (C) or ranitidine (60 mg.kg(-1)) p.o. The AEP protected rats against HRS and ET-induced ulcers, but was not able to protect the gastric mucosa against IND-induced ulcers. When injected into the duodenal lumen, the AEP reduced total acidity and both basal and histamine-stimulated acid secretion in pylorus-ligated rats. In addition, gastric secretion from AEP-treated animals exhibited increased concentrations of nitrite and nitrate. Treatment of animals with L-NAME (120 mg.kg(-1), p.o.) prevented both the reduction of total acidity and the increase in NOx levels promoted by AEP treatment. In conclusion, AEP effectively protected the gastric mucosa and inhibited gastric acid secretion in rats, probably by involving the histaminergic pathway and an enhanced production of nitric oxide in the stomach.
Assuntos
Amaranthaceae , Úlcera Duodenal/tratamento farmacológico , Óxido Nítrico/metabolismo , Animais , Brasil , Úlcera Duodenal/etiologia , Úlcera Duodenal/metabolismo , Determinação da Acidez Gástrica , Hipotermia Induzida , Indometacina , NG-Nitroarginina Metil Éster/metabolismo , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Estresse Fisiológico/complicaçõesRESUMO
Idiopathic Parkinson's disease is a neurodegenerative disorder that affects approximately 1 % of the population over 55 years of age. The disease manifests itself through motor and nonmotor symptoms induced mainly by the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The possible mechanisms involved in this pathology include mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present study evaluated the effects of the nonselective cyclooxygenase inhibitor ibuprofen on motor and depressive-like behavior induced by rotenone in rats. Rotenone (2.5 mg/kg, i.p., for 10 days) decreased tyrosine hydroxylase immunoreactivity in the SNpc, and ibuprofen treatment (15 mg/kg, p.o., for 22 days) blocked this impairment. We also found that rotenone-induced motor deficits (hypolocomotion) and depressive-like behavior, and ibuprofen was able to reverse these deficits. In addition to motor and nonmotor behaviors, we evaluated oxidative stress induced by rotenone. Rotenone administration depleted glutathione levels in the hippocampus and reduced catalase activity in both the hippocampus and striatum. Post treatment with ibuprofen blocked the depletion of glutathione induced by rotenone and increased the basal levels of this antioxidant in the striatum. Ibuprofen also restored catalase activity. The neuroprotective effects of ibuprofen against toxicity induced by rotenone appear to be attributable to its antioxidant properties, in addition to cyclooxygenase inhibition.
Assuntos
Antidepressivos/farmacologia , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Depressão/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Catalase/metabolismo , Depressão/patologia , Depressão/fisiopatologia , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Ibuprofeno , Masculino , Atividade Motora/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/psicologia , Distribuição Aleatória , Ratos Wistar , Rotenona , Superóxido Dismutase/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Prunes are the dried fruits from Prunus domestica. After the purification steps, two homogeneous polysaccharides were characterised, SF-50R and SF-50E and contained Ara:Gal:Rha:GalA in 47.8:31.5:10.7:10.0 and 39.6:50.3:5.1:5.0 molar ratios, respectively. Methylation analysis and (13)C NMR spectroscopy indicated that both fractions are constituted by rhamnogalacturonans with type I arabinogalactans as side chains, differing mainly in the proportions of the rhamnogalacturonan backbone, in the length of the (1â4)-ß-galactan chain and in the proportion of the arabinan side chain. Crude water extract (PWH) and fraction SF-50E were evaluated for their gastroprotective properties against ethanol-induced acute gastric lesions in rats. Oral administration of PWH (3 and 10mg/kg) reduced the gastric lesion area by 67±11% and 60±12%, respectively, while fraction SF-50E (10 and 30mg/kg) inhibited the lesion area by 84±12% and 83±12%, respectively. These results indicated that prune's polysaccharides act as gastroprotective agents in rats.
Assuntos
Gastrite/tratamento farmacológico , Pectinas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Prunus/química , Animais , Sequência de Carboidratos , Feminino , Gastrite/patologia , Humanos , Dados de Sequência Molecular , Pectinas/química , Substâncias Protetoras/química , Ratos , Ratos WistarRESUMO
A rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.) R.K. Jansen administered by oral route showed gastroprotective activity against acute lesions induced by ethanol. In this study, we investigated the gastric ulcer healing effect of RGal and its mechanisms of action. Intraperitoneal treatment of animals with RGal protected the gastric mucosa against acute lesions induced by ethanol, with participation of gastric mucus. Furthermore, in the chronic ulcer model, oral administration of RGal accelerates the gastric ulcer healing, accompanied by increasing of cellular proliferation and gastric mucus content, reducing inflammatory parameters and oxidative stress. In addition, the repeated 7 days-treatment of animals with RGal did not show alterations of clinical and behavioral symptoms, body and organs weights or plasmatic biochemical parameters. Collectively, these results showed that RGal has an interesting antiulcerogenic activity and could constitute an attractive molecule of interest for the development of new antiulcer agents.
Assuntos
Antiulcerosos/farmacologia , Asteraceae/química , Citoproteção/efeitos dos fármacos , Pectinas/farmacologia , Úlcera Gástrica/tratamento farmacológico , Estômago/efeitos dos fármacos , Ácido Acético/efeitos adversos , Animais , Antiulcerosos/uso terapêutico , Antioxidantes/metabolismo , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Etanol/efeitos adversos , Feminino , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa/metabolismo , Mucinas/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Pectinas/uso terapêutico , Ratos , Ratos Wistar , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologiaRESUMO
A fucomannogalactan (FMG-Am) and a (1â3), (1â6)-linked ß-D-glucan (ßGLC-Am) were isolated from Amanita muscaria fruiting bodies. These compounds' structures were determined using mono- and bi-dimensional NMR spectroscopy, methylation analysis, and controlled Smith degradation. FMG-Am was shown to be a heterogalactan formed by a (1â6)-linked α-D-galactopyranosyl main chain partially substituted at O-2 mainly by α-L-fucopyranose and a minor proportion of ß-D-mannopyranose non-reducing end units. ßGLC-Am was identified as a (1â3)-linked ß-D-glucan partially substituted at O-6 by mono- and a few oligosaccharide side chains, which was confirmed after controlled Smith degradation. Both the homo- and heteropolysaccharide were evaluated for their anti-inflammatory and antinociceptive potential, and they produced potent inhibition of inflammatory pain, specifically, 91±8% (30 mg kg(-1)) and 88±7% (10 mg kg(-1)), respectively.