RESUMO
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
ETHNOPHARMACOLOGICAL RELEVANCE: Piper tuberculatum Jacq. (Piperaceae) is medicinally used as an analgesic and as a treatment for gastric complaints. Thus, the current study aimed to investigate the gastroprotective and antisecretory properties of the dichloromethane fraction of the fruit of Piper tuberculatum (DFPT) and piplartine, a compound isolated from the DFPT, in rats. MATERIALS AND METHODS: Gastric ulcers were induced in fasted rats by oral administration of absolute ethanol and then mucus content and glutathione (GSH) levels were measured. Mechanisms underlying the antisecretory action were studied through gastric H(+),K(+)-ATPase activity of highly purified rabbit gastric microsomes and pylorus ligature method in rats. RESULTS: In the acute toxicity test the values of estimated LD50 for oral and intraperitoneal administration of DFPT were 1.6266 and 0.2684g/kg, respectively. The DFPT (ED50=29mg/kg, p.o.) and piplartine (4.5mg/kg, p.o.) promoted gastroprotection against acute lesions induced by ethanol, effect that could be related with the maintenance of GSH levels in the gastric mucosa. However, only DFPT stimulated gastric mucus secretion. In vitro, the DFPT and piplartine inhibited the H(+),K(+)-ATPase activity and, in vivo DFPT and piplartine also reduced basal gastric acid secretion, as well as that stimulated by pentagastrin. CONCLUSIONS: These results demonstrate that DFPT and piplatine cause marked gastroprotective effects accompanied by the increase and maintenance of gastric mucus and GSH levels, as well as a reduction in gastric acid secretion through the gastrinergic pathway.
Assuntos
Antiulcerosos/uso terapêutico , Piper , Piperidonas/uso terapêutico , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Etanol , Feminino , Frutas/química , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Cloreto de Metileno/química , Camundongos , Muco/metabolismo , Fitoterapia , Piperidonas/farmacologia , Extratos Vegetais/farmacologia , Coelhos , Ratos , Ratos Wistar , Solventes/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismoRESUMO
We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms.
Assuntos
Antiulcerosos/farmacologia , Arctium/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Ácido Acético/toxicidade , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Permeabilidade Capilar/efeitos dos fármacos , Etanol/química , Feminino , Radicais Livres/metabolismo , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa/metabolismo , Peroxidase/metabolismo , Fenóis/análise , Extratos Vegetais/química , Raízes de Plantas/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/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
ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia has been widely used in Brazilian folk medicine as an anti-hypertensive agent. We evaluated the vascular effects and mechanism involved in the relaxation of aorta induced by an n-butanolic fraction (BuOH) from Scutia buxifolia. MATERIALS AND METHODS: Rat aortic rings precontracted by phenylephrine (1 µM) were exposed to cumulative concentrations (33000 µg/ml) of crude extracts or fractions obtained from bark or leaves of Scutia buxifolia. Classical receptor antagonists, channel and enzymatic inhibitors were used to check the mechanisms involved. RESULTS: The crude extracts of both leaves and bark of Scutia buxifolia, as well as several fractions, were able to induce partial or total relaxation of rat aortic rings. The BuOH fraction of bark of Scutia buxifolia was the most potent in endothelium-intact (E+) preparations, and also induced a partial, but very significant relaxation in endothelium-denuded (E−) vessels. The non-selective nitric oxide synthase inhibitor L-NAME, as well as the soluble guanylate cyclase inhibitor ODQ, vanished the relaxation in E+. In E− preparations, K+ channel blockers, such as tetraethylammonium, glibenclamide, 4-aminopyridine, and the large-conductance calcium-activated K+ channel blocker iberiotoxin, were able to significantly reduce the maximum relaxation elicited by BuOH fraction. CONCLUSION: Our results demonstrated that BuOH fraction obtained from barks of Scutia buxifolia induced both endothelium-dependent and -independent relaxation in rat aortic rings. The endothelium-dependent relaxation is fully dependent on NO/cGMP system, while direct activation of K+ channels may explain, at least in part, the endothelium-independent relaxation induced by BuOH fraction of Scutia buxifolia.
Assuntos
Aorta Torácica/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rhamnaceae , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/farmacologia , 1-Butanol/química , Animais , Aorta Torácica/fisiologia , Cálcio/fisiologia , GMP Cíclico/fisiologia , Endotélio Vascular/fisiologia , Técnicas In Vitro , Masculino , Óxido Nítrico/fisiologia , Casca de Planta , Folhas de Planta , Canais de Potássio Cálcio-Ativados/fisiologia , Ratos , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have shown that the extracts obtained from Tropaeolum majus L., and its main compound isoquercitrin (ISQ), exhibit pronounced diuretic effects, supporting the ethnopharmacological use of this plant. The aim of this study was to evaluate the efficacy and mechanisms underlying the diuretic action of an ethanolic extract of Tropaeolum majus (HETM), its purified fraction (TMLR), and its main compound ISQ, in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: The diuretic effects of HETM (300mg/kg; p.o.), TMLR (100mg/kg; p.o.), and ISQ (10mg/kg; p.o.), were compared with classical diuretics in 7days repeated-dose treatment. The urinary volume, sodium, potassium, chloride, bicarbonate, conductivity, pH and density were estimated in the sample collected for 15h. The plasmatic concentration of sodium, potassium, urea, creatinine, aldosterone, vasopressin, nitrite and angiotensin converting enzyme (ACE) activity were measured in samples collected at the end of the experiment (seventh day). Using pharmacological antagonists or inhibitors, we determine the involvement of bradykinin, prostaglandin and nitric oxide (NO) in ISQ-induced diuresis. In addition, reactive oxygen species (ROS) and the activity of erythrocytary carbonic anhydrase and renal Na(+)/K(+)/ATPase were evaluated in vitro. RESULTS: HETM, TMLR and ISQ increased diuresis similarly to spironolactone and also presented K(+)-sparing effects. All groups presented both plasmatic aldosterone levels and ACE activity reduced. Previous treatment with HOE-140 (a B2-bradykinin receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or L-NAME (a NO synthase inhibitor), fully avoided the diuretic effect of ISQ. In addition, the 7days treatment with ISQ resulted in increased plasmatic levels of nitrite and reducing ROS production. Moreover, the renal Na(+)/K(+)/ATPase activity was significantly decreased by ISQ. CONCLUSION: Our results suggest that the mechanisms through ISQ and extracts of Tropaeolum majus increase diuresis in SHR rats are mainly related to ACE inhibition, increased bioavailability of bradykinin, PGI2, and nitric oxide, besides an inhibitory effect on Na(+)/K(+)-ATPase.
Assuntos
Diurese/efeitos dos fármacos , Diuréticos/farmacologia , Hipertensão/tratamento farmacológico , Extratos Vegetais/farmacologia , Quercetina/análogos & derivados , Tropaeolum , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Biomarcadores/metabolismo , Bradicinina/metabolismo , Modelos Animais de Doenças , Diuréticos/isolamento & purificação , Epoprostenol/metabolismo , Etanol/química , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Natriurese/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Quercetina/isolamento & purificação , Quercetina/farmacologia , Ratos , Ratos Endogâmicos SHR , Transdução de Sinais/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Solventes/química , Fatores de Tempo , Tropaeolum/químicaRESUMO
ß-D-Glucan, a polysaccharide isolated from an edible mushroom Pleurotus pulmonarius (Fr.) Quel., presented antinociceptive activity in mice. This study evaluated the involvement of transient receptor potential (TRP) channels and protein kinase C (PKC) on antinociceptive effect of a (1â3),(1â6)-linked ß-D-glucan (GL) in mice. Intraperitoneal administration of GL potently inhibited nociceptive responses induced by intraplantar injections of capsaicin, cinnamaldehyde, menthol, acidified saline and phorbol myristate acetate (PMA). Moreover, Western blot analysis revealed that GL treatment also prevented PMA-induced PKCÉ activation. Collectively, present results demonstrate that GL could constitute an attractive molecule of interest for the development of new analgesic drugs.
Assuntos
Analgésicos/farmacologia , Glucanos/farmacologia , Pleurotus/química , Proteína Quinase C/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Canais Iônicos Sensíveis a Ácido , Acroleína/análogos & derivados , Acroleína/farmacologia , Analgésicos/isolamento & purificação , Animais , Capsaicina/farmacologia , Ativação Enzimática/efeitos dos fármacos , Glucanos/isolamento & purificação , Masculino , Mentol/farmacologia , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Nociceptividade/efeitos dos fármacos , Proteína Quinase C/metabolismo , Inibidores de Proteínas Quinases/isolamento & purificação , Canais de Sódio/metabolismo , Canais de Cátion TRPV/metabolismo , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
H+, K(+)-ATPase enzyme is a therapeutic target for the treatment of gastric disturbances. Several medicinal plants and isolated compounds inhibit the acid gastric secretion through interaction with the proton pump. In order to add new properties to some natural constituents, five compounds, a benzylated derivative of vincoside, a diterpene (abietic acid) and three alkaloids (cephaeline, vinblastine and vindoline), were tested for their activities on gastric H+, K(+)-ATPase isolated from rabbit stomach. All the compounds inhibited H+, K(+)-ATPase activity with varied potency. The IC50 value for benzylvincoside was 121 (50-293) microM, and for abietic acid 177 (148-211) microM. The alkaloids cephaeline, vinblastine and vindoline inhibited the H+, K(+)-ATPase activity with IC50 values of 194, 761 and 846 microM, respectively. The results suggest that benzylvincoside, abietic acid and cephaeline can be important sources for the development of anti-secretor agents.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Plantas Medicinais/química , Inibidores da Bomba de Prótons , Animais , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Masculino , CoelhosRESUMO
OBJECTIVES: This study aimed to investigate the in-vitro and in-vivo cardiovascular effects of the crude hydroalcoholic extract from Polygala paniculata (HEPP) in rats. METHODS: The procedures were performed on aortic rings and on normotensive anaesthetized rats. KEY FINDINGS: When tested in endothelium-intact aorta rings, HEPP (30-1000 µg/ml) produced a significant non-concentration-dependent relaxing effect (â¼40%), which was completely prevented by incubation with L-NAME (nitric oxide synthase inhibitor), ODQ (soluble guanylate cyclase inhibitor) and partially inhibited by tetraethylammonium (TEA; a non-selective potassium channel blocker) and charybdotoxin (a large- and intermediate-conductance calcium-activated potassium channel blocker). In contrast, atropine (a muscarinic receptor antagonist) or pyrilamine(a histamine H1 receptor antagonist) had no effect. Furthermore, oral administration of HEPP (30-300 mg/kg) in anaesthetized rats caused a dose-dependent and sustained hypotensive action. This effect was unchanged by atropine or TEA, but was strongly reduced in rats continuously infused with L-NAME or methylene blue. Moreover, rutin (1-3 mg/kg) administered by an intravenous route also caused a dose-dependent hypotensive effect in rats. CONCLUSIONS: Our results demonstrated that the extract obtained from P. paniculata induces potent hypotensive and vasorelaxant effects that are dependent on the nitric oxide/guanylate cyclase pathway. These effects could be related, at least in part, to the rutin contents in this extract.
Assuntos
Anti-Hipertensivos/farmacologia , Extratos Vegetais/farmacologia , Polygala/química , Rutina/farmacologia , Vasodilatadores/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Atropina/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Guanilato Ciclase/antagonistas & inibidores , Masculino , Azul de Metileno/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Fitoterapia , Bloqueadores dos Canais de Potássio/farmacologia , Pirilamina/farmacologia , Ratos , Ratos WistarRESUMO
Traditional uses of Achillea millefolium L. (Asteraceae) include the treatment of cardiovascular diseases. In the present study, we used anesthetized rats to assess the hypotensive effect of a hydroethanolic extract (HEAM), and its dichloromethane (DCM), ethyl acetate (EA), butanolic (BT), and dichloromethane-2 (DCM-2) fractions, besides the flavonoid artemetin, isolated from A. millefolium. The oral administration of HEAM (100-300 mg/kg), DCM (20mg/kg), DCM-2 (10-30 mg/kg), but not EA (10 mg/kg) and BT (50 mg/kg) fractions significantly reduced the mean arterial pressure (MAP) of normotensive rats. The phytochemical analysis by NMR (1)H of DCM and DCM-2 fractions revealed high amounts of artemetin, that was isolated and administered by either oral (1.5 mg/kg) or intravenous (0.15-1.5 mg/kg) routes in rats. This flavonoid was able to dose-dependently reduce the MAP, up to 11.47 ± 1.5 mmHg (1.5 mg/kg, i.v.). To investigate if artemetin-induced hypotension was related to angiotensin-converting enzyme inhibition, we evaluated the influence of this flavonoid on the vascular effects of both angiotensin I and bradykinin. Intravenous injection of artemetin (0.75 mg/kg) significantly reduced the hypertensive response to angiotensin I while increased the average length of bradykinin-induced hypotension. Artemetin (1.5 mg/kg, p.o.) was also able to reduce plasma (about 37%) and vascular (up to 63%) ACE activity in vitro, compared to control group. On the other hand, artemetin did not change angiotensin II-induced hypertension. Our study is the first showing the hypotensive effects induced by the extract and fractions obtained from A. millefollium. In addition, our results disclosed that this effect may be, at least in part, associated with high levels of artemetin and its ability to decrease angiotensin II generation in vivo, by ACE inhibition.
Assuntos
Achillea/química , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Flavonoides/uso terapêutico , Extratos Vegetais/uso terapêutico , Análise de Variância , Angiotensina I/efeitos adversos , Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Bradicinina/uso terapêutico , Hipertensão/tratamento farmacológico , Masculino , Cloreto de Metileno/química , Cloreto de Metileno/uso terapêutico , Óleos Voláteis/uso terapêutico , Peptidil Dipeptidase A/metabolismo , Fitoterapia , Extratos Vegetais/química , Ratos , Ratos WistarRESUMO
The in vivo and in vitro effects of the pesticide endosulfan on the cholinesterase (ChE) activity were investigated in rats. ChE activity decreased in dams and in male pups within 65 days corresponding to 35% and 32% of inhibition respectively in the higher endosulfan dose (1.5 mg/kg). In vitro, the enzyme activity was found to be inhibited in a concentration dependent manner. The results suggest that endosulfan is able to inhibit the ChE activity and to cross the placental barrier and/or to be eliminated through milk affecting the enzyme activity in male rat pups.
Assuntos
Inibidores da Colinesterase/toxicidade , Colinesterases/metabolismo , Endossulfano/toxicidade , Inseticidas/toxicidade , Animais , Animais Recém-Nascidos , Relação Dose-Resposta a Droga , Feminino , Masculino , Exposição Materna , Ratos , Ratos WistarRESUMO
AIM OF THE STUDY: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic properties. In the present study, we assessed whether the hypotensive and/or antihypertensive mechanism of hydroethanolic extract (HETM), semi-purified fraction (TMLR) obtained from T. majus and the flavonoids isoquercitrin (ISQ) and kaempferol (KPF) can be mediated by their interaction with angiotensin converting enzyme (ACE). METHODS AND METHODS: Firstly, to evaluate changes in mean arterial pressure (MAP), different groups of normotensive and spontaneously hypertensive rats (SHR) were orally and intraduodenally treated with HETM (10-300 mg/kg) and TMLR (12.5-100mg/kg) and intravenously treated with ISQ and KPF being later anesthetized with ketamine (100mg/kg) and xylazine (20mg/kg). The left femoral vein and the right carotid artery were isolated, and polyethylene catheters were inserted for ISQ and KPF (0.5-4 mg/kg) administration and blood pressure recording, respectively. The plasmatic ACE activity was evaluated to indirect fluorimetry, in serum samples after orally treatment with HETM, TMLR, ISQ and KPF. RESULTS: The oral administration of the HETM and its TMLR significantly reduced, in a dose-dependent manner, the MAP in both normotensive and SHR. In addition, these preparations significantly decreased the MAP for up to 3h after the administration of the extract. Additionally, the intravenous administration of ISQ, but not KPF, decreased MAP in rats. Otherwise, neither the extracts nor ISQ affected the heart rate. The oral administration of the HETM, TMLR or ISQ reduced ACE activity in serum samples at 90 min after administration. Finally, the intravenous administration of ISQ caused a significant reduction in the hypertensive response to angiotensin I, but not angiotensin II in normotensive rats. CONCLUSION: Our results show that the hypotensive effects caused by the HETM, as well as by its TMLR, may be associated with the high levels of the flavonoid ISQ found in this plant. In addition, ISQ-induced hypotension in rats is an event dependent on the inhibition of angiotensin II generation by ACE.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Quercetina/análogos & derivados , Tropaeolum/química , Angiotensina I/antagonistas & inibidores , Inibidores da Enzima Conversora de Angiotensina/análise , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/análise , Anti-Hipertensivos/uso terapêutico , Relação Dose-Resposta a Droga , Hipertensão/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Quercetina/análise , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Ratos WistarRESUMO
AIM OF THE STUDY: Previous studies have shown that the extracts obtained from Tropaeolum majus L. exhibit pronounced diuretic effects supporting the ethnopharmacological use of this plant as diuretic. In the present work, phytochemical investigation, guided by bio-assay in spontaneously hypertensive rats (SHR), was carried out in order to identify the compounds responsible for diuretic action. MATERIAL AND METHODS: Chromatographic fractionation of the hydroethanolic extract yielded an active fraction (TMLR) rich in isoquercitrin. TMLR (25-100mg/kg) and isoquercitrin (5-10mg/kg), as well the reference drug hydrochlorothiazide (10mg/kg) were orally administered in a single dose or daily for 7 days to SHR. The urine excretion rate, pH, density, conductivity and content of sodium (Na(+)) and potassium (K(+)) electrolytes were measured in the urine of saline-loaded animals. RESULTS: The urinary excretion rate was dose-dependently increased in both TMLR and isoquercitrin groups, as well as Na(+). Despite the changes in urinary excretion of electrolytes, the plasmatic levels of Na(+) and K(+) had not been changed. In addition, we did not find any evidence of renal toxicity or other adverse effects in these animals, even after prolonged treatment with TMLR or isoquercitrin. CONCLUSION: This research supports and extends the ethnomedicinal use of T. majus as diuretic. This activity seems to be associated to the presence of the flavonol isoquercitrin.
Assuntos
Diuréticos/farmacologia , Hipertensão/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Potássio/metabolismo , Quercetina/análogos & derivados , Tropaeolum/química , Animais , Diuréticos/isolamento & purificação , Relação Dose-Resposta a Droga , Hidroclorotiazida/farmacologia , Hipertensão/sangue , Hipertensão/urina , Masculino , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta , Potássio/sangue , Potássio/urina , Quercetina/isolamento & purificação , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Sódio/sangue , Sódio/urina , Micção/efeitos dos fármacosRESUMO
UNLABELLED: The present study evaluated the antinociceptive effect of (1â3),(1â6)-linked ß-glucan (GL) isolated from Pleurotus pulmonarius (Fr.) Quel. in mice and its possible mechanism of action. Intraperitoneal administration of GL inhibited glutamate-induced licking with an ID(50) of 0.34 mg/kg and inhibition of 96% ± 3%. The treatment of animals with GL (1 mg/kg i.p.) inhibited nociception induced by intrathecal injection of N-methyl-D-aspartic acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate and interleukin -1ß in 67% ± 13%, 89% ± 11%, 74% ± 9%, and 75% ± 7%, respectively, but not the nociceptive response induced by (±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, substance P, and tumor necrosis factor-α. Moreover, GL (30 mg/kg i.p.) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 2 hours, with inhibition of 47% ± 10% observed 0.5 hours after treatment. When given chronically (twice a day) over 7 days, GL reversed the mechanical allodynia caused by partial sciatic nerve ligation (inhibition of 45% ± 13% to 60% ± 8%). Interestingly, GL did not affect the locomotor activity of mice in an open field test with doses that produce antinociceptive effects. Our findings show that GL inhibits acute and neuropathic pain in mice through mechanisms that involve the inhibition of ionotropic glutamate receptors and the interleukin -1ß pathway. PERSPECTIVE: This article presents the antinociceptive activity of GL in acute and neuropathic pain with participation of ionotropic glutamate receptors and pro-inflammatory cytokines (interleukin-1ß). After further experiments, this compound may represent a new pharmacological agent for the treatment of clinical pain.
Assuntos
Analgésicos/farmacologia , Glucanos/farmacologia , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Pleurotus/química , Receptores de Glutamato/fisiologia , Transdução de Sinais/efeitos dos fármacos , Doença Aguda , Analgésicos/uso terapêutico , Animais , Citocinas/fisiologia , Modelos Animais de Doenças , Feminino , Glucanos/uso terapêutico , Injeções Intraperitoneais , Interleucina-1beta/fisiologia , Masculino , Camundongos , Neuralgia/fisiopatologia , Transdução de Sinais/fisiologiaRESUMO
UNLABELLED: Achillea millefolium L. is a member of the Asteraceae family that is commonly referred to as "yarrow" and has been used in folk medicine against several disturbances including skin inflammations, spasmodic and gastrointestinal disorders, as well as hepato-biliary complaints. AIM OF THE STUDY: In the present study, we evaluated the efficacy of a hydroalcoholic extract from the Achillea millefolium (HE) for gastroprotective properties and additional mechanism(s) involved in this activity. MATERIAL AND METHODS: Rats were treated with HE and subsequently exposed to both acute gastric lesions induced by ethanol P.A. and chronic gastric ulcers induced by 80% acetic acid. Following treatment, glutathione (GSH) levels and superoxide dismutase (SOD) activity were measured. The activity of myeloperoxidase (MPO) and histological and immunohistochemical analysis were performed in animals with acetic acid-induced gastric ulcers. RESULTS: Oral administration of HE (30, 100 and 300mg/kg) inhibited ethanol-induced gastric lesions by 35, 56 and 81%, respectively. Oral treatment with HE (1 and 10mg/kg) reduced the chronic gastric ulcers induced by acetic acid by 43 and 65%, respectively, and promoted significant regeneration of the gastric mucosa after ulcer induction denoting increased cell proliferation, which was confirmed by PCNA immunohistochemistry. HE treatment prevented the reduction of GSH levels and SOD activity after acetic acid-induced gastric lesions. In addition, HE (10mg/kg) inhibited the MPO activity in acetic acid-induced gastric ulcers. CONCLUSIONS: The results of the present study indicate that the antioxidant properties of HE may contribute to the gastroprotective activity of this extract.
Assuntos
Achillea/química , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Etanol/química , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Glutationa/metabolismo , Imuno-Histoquímica , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/prevenção & controle , Superóxido Dismutase/metabolismoRESUMO
Monosialotetrahexosylganglioside (GM1) is a glycosphingolipid present in most cell membranes that displays antioxidant and neuroprotective properties. It has been recently described that GM1 induces pial vessel vasodilation and increases NO( x ) content in cerebral cortex, which are fully prevented by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). However, it is not known whether GM1 relaxes larger vessels, as well as the mechanisms by which GM1 causes vasorelaxation. In this study, we demonstrate that GM1 (10, 30, 100, 300 microM, 1 and 3 mM) induces vascular relaxation determined by isometric tension studies in rat mesenteric artery rings contracted with 1 microM phenylephrine. The vasorelaxation induced by GM1 was abolished by endothelium removal, by incubation with L-NAME (1 microM), and partially inhibited by the blockade of potassium channels by 1 mM tetraethylammonium, 10 microM glibenclamide, by the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (10 microM), and by 50 nM charybdotoxin, a blocker of large and intermediate conductance calcium-activated potassium channels. Moreover, GM1-induced relaxation was not affected by apamin (50 nM), a small conductance calcium-activated potassium channel blocker. The results indicate that direct and indirect nitric oxide pathways play a pivotal role in vasorelaxation induced by GM1, which is mediated mainly by potassium channels activation. We suggest that vasodilation may underlie some of the biological effects of exogenous GM1 ganglioside.
Assuntos
Gangliosídeo G(M1)/farmacologia , Óxido Nítrico/metabolismo , Canais de Potássio/metabolismo , Vasodilatação/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Guanilato Ciclase/metabolismo , Técnicas In Vitro , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Ratos , Ratos Wistar , Vasodilatadores/farmacologiaRESUMO
The gastrointestinal activity of hydroalcoholic extract (HE) of Salvia officinalis was evaluated in a model of ethanol-induced gastric lesion. HE showed excellent activity, with ID(50) 84.0 (54.8-128.9) mg/kg. The acetic acid-induced ulcer and the total acidity of the gastric secretion were also reduced by HE, and, in vitro experiments, the H(+),K(+)-ATPase activity was inhibited. Carnosol was identified as a possible active constituent for the gastroprotective effect of HE.
Assuntos
Abietanos/uso terapêutico , Antiulcerosos/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Salvia officinalis/química , Úlcera Gástrica/tratamento farmacológico , Abietanos/isolamento & purificação , Abietanos/farmacologia , Ácido Acético , Animais , Antiulcerosos/isolamento & purificação , Antiulcerosos/farmacologia , Etanol , Feminino , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Inibidores da Bomba de Prótons , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamenteRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex. Reissek (Celastraceae) is widely used in Brazilian folk medicine to treat gastric disturbances. AIM OF THE STUDY: This work intended to characterize the effects of Maytenus ilicifolia on gastrointestinal motility. MATERIALS AND METHODS: Gastric emptying and intestinal transit were measured in the same animal. Mice received a semisolid marked with phenol red, half an hour after treatment with extracts. The amount of marker in the stomach and the distance reached in the intestine after 15 min were measured as index of gastrointestinal emptying and intestinal transit, respectively. RESULTS: Intraperitoneal administration of a flavonoid-rich extract potently reduced the gastric emptying (ED(50)=89 mg/kg) and the intestinal transit (ED(50)=31 mg/kg) of mice. Bio-guided purification of the flavonoid-rich extract by chemical partition with solvents of decreasing polarity yielded fraction insF with about 12-14 times higher activity than the initial flavonoid extract in both the gastric emptying and the intestinal transit. The inhibitory effects of the insF (9.7 mg/kg, i.p.) on gastric emptying and intestinal transit were reversed by co-administration of bethanechol (10 mg/kg, s.c.) but not by co-administration of metoclopramide (30 mg/kg, p.o.) indicating muscarinic but not dopaminergic interaction of the compounds of Maytenus. Chemical investigation of the insF fraction by HPLC-MS allowed the identification of 4 free flavonoids (catechin, epicatechin, quercetin and kaempferol), 29 flavonol glycosides and 8 tannins. The flavonol glycosides ranged from 1 to 4 monosaccharide units, having mainly quercetin and kaempferol as aglycone moieties, and the tannins were composed by catechin/epicatechin and/or afzelechin/epiafzelechin. CONCLUSIONS: Overall, the results indicate that the components of Maytenus ilicifolia have a potential use in the treatment of gastrointestinal motility disturbances such as diarrhea.
Assuntos
Colinérgicos/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Maytenus , Extratos Vegetais/farmacologia , Animais , Betanecol/farmacologia , Colinérgicos/administração & dosagem , Colinérgicos/química , Feminino , Flavonoides/farmacologia , Flavonóis/farmacologia , Glicosídeos/farmacologia , Injeções Intraperitoneais , Maytenus/química , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Taninos/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia glomerata (Spreng) Pedersen (Amaranthaceae) is a medicinal plant known in Brazil as "Paratudo" and "Brazilian ginseng" and is commonly used as tonic, antidiabetic and to treat gastric disorders. AIM OF THE STUDY: This study evaluates the possible mechanism by which hydroalcoholic extract (HE) of Pfaffia glomerata exerts its antinociceptive effect. MATERIALS AND METHODS: The HE was evaluated in acetic acid and glutamate models of pain or by biting behavior following intrathecal (i.t.) administration of agonists of excitatory aminoacids (EAA) receptors glutamate and pro-inflammatory cytokines, IL-1beta and TNF-alpha in mice. RESULTS: Oral administration of HE produced dose-dependent inhibition of acetic acid-induced visceral pain and glutamate-induced pain, with ID(50) of 64.6 (47.7-87.5)mg/kg and ID(50) of 370.8 (253.4-542.7)mg/kg, respectively. The HE (300 mg/kg, p.o.) antinociception, in the acetic acid test, was not affected by i.p. treatment of animals with naloxone. In addition, HE (300 mg/kg, p.o.) inhibited the pain-related behaviors induced by i.t. injection of trans-ACPD and TNF-alpha, but not by NMDA, AMPA, kainate or IL-1beta. CONCLUSIONS: Our results suggest that inhibition of glutamatergic metabotropic receptors and TNF-alpha may account for the antinociceptive action reported for the HE in models of chemical pain used in this study.
Assuntos
Amaranthaceae , Analgésicos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Dor/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Ácido Acético , Analgésicos/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Cicloleucina , Modelos Animais de Doenças , Agonistas de Aminoácidos Excitatórios , Feminino , Ácido Glutâmico/metabolismo , Injeções Espinhais , Interleucina-1beta , Camundongos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Dor/induzido quimicamente , Dor/metabolismo , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
UNLABELLED: Tropaeolum majus L. (Tropaeolaceae), popularly known as "chaguinha", is well recognized in Brazilian traditional medicine as diuretic agent, although no scientific data have been published to support this effect. AIM OF THE STUDY: To evaluate the diuretic activity of the infusion and the hydroethanolic extract (HETM) of Tropaeolum majus, and possible mechanism of action. MATERIAL AND METHODS: The infusions (2,5 - 10%) and the HETM doses (150, 300 mg/kg) were orally administered to rats. Urinary excretion, the electrolytes levels, and urea and creatinine were measured in of saline-loaded rats. RESULTS: The oral administration of 10% (corresponding to 500 mg/kg) of the infusion increased significantly the urinary Na(+) excretion. Only the oral administration of 300 mg/kg of HETM increased significantly the urinary and Na(+) excretion. Prolonged administration of the HETM (300 mg/kg) significantly increased diuresis and the urinary excretion of Na(+), but others parameters were unaffected. To gain some evidence in possible involvement of prostaglandins system in diuretic action, the oral administration of HETM (300 mg/kg) in association indomethacin (5mg/kg) reduced the urinary and sodium excretion when compared only HETM group. CONCLUSION: The results suggest that HETM could present compound(s) responsible for diuretic activities with no signs of toxicity, and the mechanism could involve prostaglandin system.