RESUMO
Plants with medicinal potential may also produce adverse effects in humans. This seems to be the case for the species Rubus rosifolius, where preliminary studies demonstrated genotoxic effects attributed to extracts obtained from leaves and stems of this plant using on HepG2/C3A human hepatoma cells as a model. Considering the beneficial properties of this plant as an antidiarrheal, analgesic, antimicrobial, and antihypertensive and its effects in the treatment of gastrointestinal diseases, the present study was developed with the aim of determining the cytotoxic and genotoxic potential of extracts of leaves and stems of R. rosifolius in primary without metabolic competence in human peripheral blood mononuclear cells (PBMC). Cell viability analyses at concentrations of between 0.01 and 100 µg/ml of both extracts did not markedly affect cell viability. In contrast, assessment of the genotoxic potential using the comet assay demonstrated significant damage to DNA within PBMC from a concentration of 10 µg/ml in the stem extract, and a clastogenic/aneugenic response without cytokinesis-block proliferation index (CBPI) alterations at concentrations of 10, 20, or 100 µg/ml for both extracts. Under our experimental conditions, the data obtained demonstrated genotoxic and mutagenic effects attributed to extracts from leaves and stems of R. rosifolius in cells in the absence of hepatic metabolism.
Assuntos
Leucócitos Mononucleares , Rubus , Humanos , Extratos Vegetais/toxicidade , Testes para Micronúcleos , Ensaio Cometa , Dano ao DNA , Mutagênicos , Folhas de PlantaRESUMO
Rubus rosifolius, popularly known as "red mulberry", is a common medicinal plant in southern Brazil and is used as an antidiarrheal, analgesic, antimicrobial and antihypertensive, and to treat stomach diseases. The aim of this study was to analyze the R. rosifolius stem extract (RrSE) for possible in vitro cytotoxic and genotoxic effects, using the comet assay and the micronucleus test to assess genotoxicity, and flow cytometry to assess the impact on the cell cycle and apoptosis in HepG2/C3A cells, in addition to evaluating the expression of genes linked to the induction of DNA damage, cell cycle, apoptosis and metabolism of xenobiotics. The MTT assay observed no cytotoxic effects at concentrations between 0.01 and 100 µg/mL of the extract. However, genotoxic effects occurred in treatments with the extract from a 1 µg/mL concentration. Flow cytometry analysis revealed a significant increase in cells in the G2/M phase after treatment with 10 µg/mL, a decrease in cells in the G0/G1 phase in the treatment with 100 µg/mL, and a significant increase in total apoptotic cells. In the gene expression analysis, an increase in the CYP1A2 xenobiotics metabolizing gene expression was observed. Despite the promising pharmacological effects of R. rosifolius, the results revealed that the RrSE has genotoxic effect and induces apoptosis in HepG2/C3A cells, indicating danger in using this plant extract by humans.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Rubus , Humanos , Apoptose , Dano ao DNA , Extratos Vegetais/toxicidade , Extratos Vegetais/análise , Células Hep G2 , Linhagem CelularRESUMO
This study evaluated the diuretic and antiurolithic effect of methanolic extract (MEGHL), dichloromethane (DCM), and ethyl acetate (EtA) fractions obtained from the leaves of Garcinia humilis, a medicinal plant known as achachairu and native to South American countries such as Bolivia, Peru, and Brazil. For the analysis of diuretic effect, the female rats received the treatment with MEGHL (3, 10, and 30â mg/kg), DCM (1, 3 and 10â mg/kg), EtA (1, 3, and 10â mg/kg), hydrochlorothiazide (HCTZ; 10â mg/kg), or vehicle (VEH) after an overload of saline solution. At the end 8â h of the experiment, the urinary parameters were measured. Additionally, the antiurolithic effect was analyzed, in which sodium oxalate was added in synthetic urine in the presence or absence of MEGHL, DCM, and EtA in different concentrations (0.1, 0.3, and 1â mg/mL). MEGHL, DCM, and EtA were able to promote 8-h diuresis in rats. MEGHL treatment at dose 30â mg/kg was accompanied by increased urinary Na+ , K+ and Cl- excretion. Moreover, the DCM and EtA fractions treatment increased K+ and Cl- excretion in the urine, although it does not cause any change in Na+ elimination. All the preparations were able to exert an antiurolithic effect inâ vitro, decreasing the number of calcium oxalate crystals of the monohydrate and dihydrate types. Taking together, the results presented herein showed that the preparations of G.â humilis leaves are promising strategies to induce diuresis and antiurolithic effects.
Assuntos
Garcinia , Plantas Medicinais , Ratos , Animais , Diuréticos/farmacologia , Diuréticos/análise , Oxalato de Cálcio/análise , Cloreto de Metileno/análise , Solução Salina , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/análise , Ratos Wistar , Folhas de Planta/química , Hidroclorotiazida/análise , Hidroclorotiazida/farmacologia , BrasilRESUMO
The previous study showed that 1,5,8-trihydroxy-4',5'-dimethyl-2H-pyrano(2,3 : 3,2)-4-(3-methylbut-2-enyl) xanthone (TDP) obtained from Garcinia achachairu Rusby (Clusiaceae) branches induces acute diuresis in normotensive (NTR) and spontaneously hypertensive rats (SHR) after 8 h of the experiment. In complementarity, the present study evaluated the prolonged diuretic and renoprotective effects of TDP in both NTR and SHR. The animals received, once a day, oral treatment with TDP (0.1 mg/kg), hydrochlorothiazide (10 mg/kg), or vehicle (VEH; 10 mL/kg). At the end of 7 days, the urine, blood, and kidney samples were collected for biochemical and histological analyzes. The urinary volume of both NTR and SHR after 7 days of treatment with the TDP was significantly increased, associated with augmented urinary electrolyte excretion levels. The treatments did not modify the urinary pH values nor the parameters analyzed in plasma (Na+, K+, Cl-, and Ca2+). Concerning the renal analyzes, when compared with the VEH-treated NTR group, while the activity of the enzymes catalase (CAT) and N-acetyl-ß-D-glucosaminidase (NAG), as well as nitrite levels, were increased, the generation of lipid hydroperoxides and the activity of the enzyme myeloperoxidase (MPO) were unaltered. On the other hand, the activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) and the levels of reduced glutathione (GSH) in kidney homogenates of the SHR group were decreased. However, TDP augmented the levels of GSH and GST activities and reduced the levels of nitrite and the activities of CAT and MPO, when compared with VEH-treated only SHR. Besides, the treatment with TDP alleviated the morphological changes of the renal corpuscle region of SHR. Together, these results revealed the prolonged diuretic effect of TDP and their renal protective effect by improving the antioxidative capacity.
RESUMO
Garcinia humilis is popularly used to treat digestive, intestinal and inflammatory illness. We investigated the in vivo and in vitro effects of the methanol extract of G. humilis leaves (MEGh) on inflammatory cells behavior (migration and chemical mediators release) and hypersensitivity. Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice treated orally with MEGh (0.1-30 mg/kg). Leucocyte migration, chemical mediators secretion (TNF, IL-1ß, IL-6 and CXCL1) and protein exudation were quantified in the exudate. The adhesion molecules expression (CD62L and CD18), chemical mediators and chemotaxis was evaluated using neutrophils or macrophages RAW.264.7 previously treated with the extract (1-100 µg/mL) and activated with LPS. The anti-inflammatory activity of the isolated compounds friedelin, canophyllol, amentoflavone and 3-desmethyl-2-geranyl-4-prenylbellidypholine xanthone (10 µM) was evaluated in macrophages nitric oxide (NO) and TNF release. MEGh, given orally (30 mg/kg), significantly reduced neutrophil migration and decreased TNF, IL-1ß and CXCL1 levels, without interfering with protein exudation and IL-6. In vitro, the extract significantly reduced IL-1ß and IL-6 levels but did not alter TNF and CXCL1. The MEGh also reduced the expression of CD62L and CD18 and consequently neutrophil chemotaxis. The compounds friedelin, amentoflavone and 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone decreased the secretion of NO and TNF by RAW264.7. The MEGh effects were extended to the pain-like behaviour induced by carrageenan in the mice hindpaw. MEGh presented important anti-inflammatory effects probably due to its activity on neutrophil migration and on important chemical mediator release, scientifically reinforcing its use as medicinal plant.
Assuntos
Anti-Inflamatórios/farmacologia , Garcinia/química , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Carragenina , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/patologia , Masculino , Metanol/química , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Extratos Vegetais/administração & dosagem , Folhas de Planta , Células RAW 264.7RESUMO
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
RUBUS ROSIFOLIUS: Sm. (Rosaceae) is a plant traditionally used in Brazil and some other countries to treat diarrhea, stomach diseases, and as an analgesic, antimicrobial, antihypertensive, and as well as other pharmacological properties. The aim of this study was to examine cytotoxic and genotoxic effects of R. rosifolius leaves extract on HepG2/C3A cells and correlate these findings with the expression of mRNA to underlying mechanisms of action. At concentrations between 0.01 and 100 µg/ml, cytotoxic effects were not detected by the MTT assay. This was confirmed by mRNA induction of the CYP3A4 gene (by RT-qPCR assay). However, genotoxic effects occurred at treatments from 1 µg/ml extract (comet and micronucleus test). An increase in the number of cells in S phase was observed at 100 µg/ml, and an elevation in apoptotic cell number was found for all tested concentrations (10, 20, or 100 µg/ml) (cell cycle and apoptosis analysis by flow cytometry). The genotoxicity induced by the extract was the main cause of the rise in the number of cells undergoing apoptosis, as indicated by rise in mRNA of CASP7 gene, and elevation of cells in the S phase of the cell cycle at the higher tested concentrations, as an attempt to repair genetic damage that occurred. These observations suggest that, despite its pharmacological potential, the use of R. rosifolius leaves extract may pose a risk to the integrity of the genetic material of human cells.
Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Dano ao DNA , Extratos Vegetais/toxicidade , Rubus/química , Brasil , Caspase 7/genética , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Testes de Mutagenicidade , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/toxicidade , Plantas Medicinais , Medição de Risco , Rubus/toxicidadeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Luehea divaricata, popularly known in Brazil as "açoita-cavalo", has been widely explored by different ethnic groups native to Brazil to treat different pathologic conditions, including inflammatory pain. However, no report could be found on the effect that extract of L. divaricata has on neuropathic pain. This is an important topic because convergent and divergent mechanisms underlie inflammatory vs. neuropathic pain indicate that there may not always be a clear mechanistic delineation between these two conditions. AIM OF THE STUDY: The study aimed to determine antioxidant activity and macronutrient composition of aqueous extract from leaves of L. divaricata, and the effect of oral administration on nociception in rats with chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain, one of the most commonly employed animal models of neuropathic pain. MATERIALS AND METHODS: The antioxidant activity of the extract was evaluated by total phenolic content and DPPH, ABTSâ+ and ORAC methods. Vitexin was determined by HPLC to show that the composition of the extract of the present study is similar to that used in previous studies with this genus. Total sugar and sucrose concentrations were assessed by the anthrone method, while glucose and triacilglycerides were determined using commercially available kits. Fructose concentration was calculated from values for total sugars, glucose and sucrose. Total protein was determined by Bradford assay. The effect on DNA strand breaking was investigated by inhibition of strand breaking of supercoiled DNA by hydroxyl radical. The antinociceptive effects of aqueous extract (100, 300, 500, and 1000â¯mg/kg, i.g.) were evaluated on thermal and mechanical thresholds for neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. We also compared the antinociceptive effect of the extract (500â¯mg/kg, i.g.) with that induced by gabapentin (50â¯mg/kg, i.g.), a first-line clinical treatment for neuropathic pain. The effect of co-administration of extract (500â¯mg/kg, i.g.) and low-dose gabapentin (30â¯mg/kg, i.g.) was also assessed. In addition, the effect of the extract on body weight, and blood and hepatic parameters were investigated to reveal possible side effects of treatment. RESULTS: The extract showed high content of total phenol; good reducing capacity for DPPH, ABTSâ+ and ORAC assays; presence of vitexin; and a high capacity to inhibit strand breaking of supercoiled DNA. The predominant sugar was sucrose, followed by glucose and fructose. Total protein was greater than triacylglycerides, with the latter being present in a trace amount in the extract. The extract increased the thermal and mechanical thresholds, which was reduced by CCI. The antinociceptive effect was comparable to gabapentin and was also found after co-administration of extract and low-dose gabapentin. No significant change was found in body weight and blood and hepatic indicators after extract treatment. CONCLUSIONS: Aqueous extract from L. divaricata leaves was as effective as gabapentin at attenuating CCI-induced neuropathic pain, indicating for first time the therapeutic potential of this species for this type of pain.
Assuntos
Malvaceae/química , Neuralgia/tratamento farmacológico , Nociceptividade/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Antioxidantes/farmacologia , Brasil , Modelos Animais de Doenças , Hiperalgesia/tratamento farmacológico , Masculino , Medição da Dor/métodos , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Neuropatia Ciática/tratamento farmacológicoRESUMO
The present work describes the evaluation of the antidepressant-like activity of the extract, fractions, and compounds obtained from the aerial parts of Solanum capsicoides. The methanolic extract (MESC) obtained by conventional maceration was partitioned with solvents of increasing polarities yielding the respective fractions of hexane (HE), dichloromethane (DCM), and ethyl acetate (EA). The dichloromethane and ethyl acetate fractions were submitted to chromatographic and spectroscopic techniques, leading to the isolation and identification of cilistadiol (1), astragalin (2), and cilistol A (3). In relation to the antidepressant activity, the extract was active against the forced swimming test (FST) at a concentration of 300 mg/kg an ED50 (deffective dose that reduces 50% of immobility time) of 120.3 (117.3-123.4) mg/kg. Similar values were observed when evaluated in the tail suspension test (TST). In addition, the results showed no influence on motor behavior when evaluated in the open field test (OFT). Based on the observed profile of the MESC, dichloromethane fraction presenting the best profile, in both FST and TST test. Likewise, the fraction also did not present motor impairment when evaluated by the OFT test. Considering that the dichloromethane fraction was more effective, the isolated compounds cilistadiol and cilistol A were evaluated in the same experimental models. In FST, both compounds had a significant antidepressant-like effect, with ED50 values of 0.22 (0.16-0.28) and 1.03 (0.89-1.18) µmol/kg, respectively. When evaluated in the TST, showed ED50 values of 0.30 (0.18-0.52) and 1.49 (1.27-1.73) µmol/kg, respectively. The isolated compounds also did not present significant differences in the motor behavior when evaluated on OFT test in comparison with the control group. No toxicological parameters were observed until the highest dose of MESC (2000 mg/kg), demonstrating safety in the use of this plant.
Assuntos
Antidepressivos/farmacologia , Antidepressivos/toxicidade , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Solanum/química , Vitanolídeos/farmacologia , Vitanolídeos/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Elevação dos Membros Posteriores , Cloreto de Metileno , Camundongos , Atividade Motora/efeitos dos fármacos , Solventes , Natação/psicologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Popular medicine use stems of Philodendron bipinnatifidum (Araceae) in inflammation cases, such as in erysipelas, as well as orchitis and rheumatism treatment. The present study, conducted for the first time in literature, investigate the antinociceptive and anti-inflammatory activities of P. bipinnatifidum stems ethyl acetate extract (EPB). MATERIALS AND METHODS: GC/MS and HPLC analysis were performed for EPB extract. We used EPB at 250, 375 and 500â¯mg/kg (oral route, p.o.) in male Swiss mice. The antinociceptive activity of the plant extract assessed by acetic acid induced writhing and formalin tests. To investigate the possible participation of opioid system in EPB-mediated effects, we previously administered naloxone to the mice. Anti-inflammatory activity was evaluated using carrageenan-induced paw oedema. The open-field test aimed to investigate the possible EPB effects on the locomotor and exploratory activities. To assess the protective role of EPB on carrageenan-induced oxidative stress, the levels of NPSH, TBARS, as well as SOD and CAT activities were evaluated in blood and paw tissue. The acute toxicity of the EPB was investigated using OECD 423 guideline. RESULTS: The EPB chemical analysis by GC/MS and HPLC revealed the presence of flavonoids (luteolin and quercetin) and phytosterols (ß-sitosterol and stigmasterol). The oral treatment with the EPB inhibited mice abdominal writhings (Pâ¯<â¯0.01) at 375 and 500â¯mg/kg, and reduced the formalin effect at the first-phase (500â¯mg/kg, Pâ¯<â¯0.05) and also at the second-phase (500â¯mg/kg, Pâ¯<â¯0.001) of the test. EPB (375 and 500â¯mg/kg) did not alter spontaneous locomotion in open field test, however the number of fecal bolus was significantly lower for the EPB group at 500â¯mg/kg when compared to the vehicle group (Pâ¯<â¯0.05). The pretreatment with naloxone caused significant inhibition of antinociceptive activity induced by EPB in the formalin test, revealing the possible involvement of opioid receptors. EPB extract administered at 500â¯mg/kg (p.o.) prevented carrageenan-induced paw oedema (Pâ¯<â¯0.05 and 0.01) until 6â¯h after carragenan injection. Evaluation of TBARS and NPSH levels, SOD and CAT activities in the blood and paw tissue of animals submitted to the carrageenan assay suggested that the anti-inflammatory effect of EPB may be linked to oxidative stress inhibition. The acute administration of the EPB (2000â¯mg/kg, p.o.) caused no mortality, demonstrating low toxicity. CONCLUSIONS: The extract of P. bipinnatifidum displays antinociceptive and anti-inflammatory activities, causing no toxicological effects. The pharmacological activity of this vegetal species may be related to the presence of flavonoids and phytosterols. Our results support the ethnomedical use of this vegetal species as analgesic and anti-inflammatory agent.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Dor/tratamento farmacológico , Philodendron/química , Extratos Vegetais/uso terapêutico , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inflamação , Masculino , Camundongos , Dor/induzido quimicamente , Fitoterapia , Extratos Vegetais/isolamento & purificaçãoRESUMO
Several studies have suggested that (-)-epicatechin-containing foods and plant extracts benefit conditions that affect the cardiovascular system, such as hypertension and endothelial dysfunction. However, no study was conducted so far to evaluate the potential of this flavonoid on diuretic activity assay. For that, female Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) received a single oral treatment with (-)-epicatechin (EPI), hydrochlorothiazide (HCTZ) or just vehicle (VEH). The effects of EPI in combination with diuretics for clinical use, as well as with L-NAME, atropine and indomethacin were also explored. Cumulative urine volume, plasma and urinary parameters were evaluated at the end of 8 h experiment. When given to NTR and SHR, at doses of 0.3, 1 and 3 mg/kg, EPI was able to stimulate both diuresis and saluresis (Na+, K+ and Cl-), without interfering with plasma electrolyte content or urinary pH and uric acid values, when compared with VEH-treated only rats. The combination with HCTZ, but not with furosemide or amiloride, successfully strengthened EPI-induced diuresis. This effect was not accompanied by a potentiation of the saluretic effects. On the other hand, when given EPI in combination with amiloride, a significant increase in Cl- excretion and maintenance of the potassium-sparing effects characteristic of this class of diuretics were detected. In addition, the diuretic effect of EPI was enhanced after pretreatment with L-NAME and its action was significantly precluded in the presence of indomethacin, a cyclooxygenase inhibitor. In conclusion, this study shows the diuretic and saluretic properties of EPI in rats, adding another biological activity whose effect may contribute to the different positive actions already described.
Assuntos
Catequina/farmacologia , Diuréticos/farmacologia , Natriuréticos/farmacologia , Administração Oral , Animais , Atropina/farmacologia , Catequina/administração & dosagem , Catequina/química , Diuréticos/administração & dosagem , Eletrólitos/sangue , Feminino , Indometacina/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Ratos Endogâmicos SHR , Ratos WistarRESUMO
ETHOPHARMACOLOGICAL RELEVANCE: The Persea major (Meisn.) L.E. Kopp (Lauraceae) (botanical synonym: Persea pyrifolia (D. Don) Spreng, Persea pyrifolia Nees and Mart., Persea cordata var. major (Meisn.) Mez and Persea willdenovii Kosterm) is a medicinal plant native in the south of Brazil, where is popularly known as Pau de Andrade, Maçaranduba or Abacate-do-Mato. Its barks are commonly used to prepare an infusion which is administered orally or topically to treat ulcers and wounds, respectively. Thus, this study has been undertaken to contribute to the validation of the popular use of P. major to treat of ulcerative disorders from gastrointestinal system, using different experimental models in rodents. MATERIAL AND METHODS: Firstly, ultra-performance liquid chromatography coupled to a mass spectrophotometer has been performed. Next, the potential gastroprotective of hydroalcoholic extract of P. major barks (HEPM) (30-300mg/kg) has been evaluated in ulcer models acute as: ethanol, ethanol/HCl and indomethacin-induced ulcer. The extract (300mg/kg) has been also tested in acetic acid-induced chronic ulcer model. Histological, toxicological, histochemical, oxidative stress and gastric secretion parameters were analyzed. RESULTS: The main compounds found in HEPM were polyphenols as condensed tannins, flavonoids heterosides derivatives from quercetin and kaempferol. HEPM (300mg/kg, p.o) prevented gastric lesions induced by ethanol or indomethacin in rats by 58.98% and 97.48%, respectively, compared to vehicle group (148.00±14.83mm2 and 12.07±1.61mm2, respectively). In acetic acid-induced chronic ulcer model the HEPM (300mg/kg, p.o) reduced the ulcer are by 40.58%, compared to vehicle group (127.90±12.04mm2). The healing effect was confirmed histologically, by an increase in mucin content and by the reduction in oxidative and inflammatory parameters at the ulcer site. Neither significant effect on gastric acid secretion nor toxicological effects and cytotoxicity were provoked by administration of HEPM. CONCLUSIONS: The results allows to conclude that HEPM exerts gastroprotective and gastric cicatrizing effects favoring on protective defenses, but not possess antisecretory effect in contrast to the current antiulcer therapy, besides the extract present good tolerability and absence of cytotoxicity. Moreover, the results presented here contribute to the validation to the popular use of the P. major in the treatment of gastric ulcer.
Assuntos
Antiulcerosos/farmacologia , Persea/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/química , Masculino , Compostos Fitoquímicos , Fitoterapia , Extratos Vegetais/química , Plantas Medicinais , Fatores de Proteção , RatosRESUMO
We investigated the hepatoprotective effect of methanolic extract from Maytenus robusta leaves in mice and HepG2 cells. The administration of CCl4 in mice promoted a deep destruction of the histological lobular structure and increased the alanine aminotransferase (ALT) serum levels by 46.25% compared with the control group (p < 0.05). The M. robusta extract reduced the hepatic histological changes and normalization the ALT levels. The antioxidant effect of M. robusta in liver tissue promoted the reduction in 31.5% on lipoperoxides levels (p < 0.05), increased by 101.5% the reduced glutathione content (p < 0.05) and increased the activity of superoxide dismutase, catalase, and glutathione-S-transferase by 21.3% (p < 0.05), 49.3% (p < 0.05), and 27.6% (p < 0.05), respectively, compared with the vehicle group. Moreover, the extract reduced hepatic inflammation by diminishing myeloperoxidase activity, TNF and interleukin-6 levels by 29.4% (p < 0.05), 46.1% (p < 0.01), and 59.5% (p < 0.0001), respectively, compared with the vehicle group. The viability of HepG2 cells after incubation with CCl4 was 29.56± 3.07%, whereas the extract (300 µg/mL) restored the viability to 65.27± 8.75% and aspartate aminotransferase levels to 41.82 ± 4.41 U/L. The extract scavenged DPPH (IC50 = 14.44 µg/mL) and ABTS (IC50 = 3.00 µg/mL) radicals and did not produce acute toxicity in mice at 2000 mg/kg. In conclusion, was confirmed the hepatoprotective potential of M. robusta by its antioxidant effects.
Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Maytenus/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Animais , Tetracloreto de Carbono/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2/efeitos dos fármacos , Humanos , CamundongosRESUMO
Although diuretics have been widely used to treat hypertension along with others cardiovascular and renal disorders, no scientific data have been recorded to support the diuretic properties of Rubus rosaefolius Sm. (Rosaceae), a plant popularly used in Brazil to treat hypertension. Male Wistar rats were orally treated with: vehicle; hydrochlorothiazide; aqueous (AERR) and methanolic (MERR) extracts; dichloromethane (DCM), hexane (HEX) and ethyl acetate (EA) fractions; and the isolated compounds 2α,3ß,19α-trihydroxy-urs-12-en-28-oic acid (TUA) and 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF). At the end of the experiment (after 8 or 24 h), urine volume and other urine or plasma parameters were measured. AERR and MERR, at 100 and 30 mg/kg, respectively, induced diuretic, natriuretic and kaliuretic effect. Additionally, the DCM and HEX, but not EA, at 10 mg/kg, also increased urine volume and Na+ and K+ excretion. Both active constituents, TUA and PMF, at doses of 1 and 3 mg/kg, showed an augmented diuretic and natriuretic index. While TUA revealed a kaliuretic action, PMF did not interfere with potassium excretion. The compounds increased urinary creatinine, but not urea, levels. TUA was able to decrease calcium excretion, as well as HCTZ, while PMF effect was associated with increased urinary prostaglandin E2 levels. The non-selective muscarinic receptor antagonist (atropine) prevented TUA-induced diuresis. In addition, indomethacin (a cyclooxygenase inhibitor) and atropine, exhibited the ability to block the diuretic effects prompted by PMF. Our study demonstrates the diuretic effect of extracts, fractions and two natural compounds obtained from R. rosaefolius leaves in rats.
Assuntos
Diuréticos/farmacologia , Flavonas/farmacologia , Extratos Vegetais/farmacologia , Rubus , Triterpenos/farmacologia , Animais , Atropina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Dinoprostona/urina , Indometacina/farmacologia , Masculino , Antagonistas Muscarínicos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Folhas de Planta , Ratos WistarRESUMO
This study investigated the effects of Rubus imperialis, a berry known as "amora-branca", in colitis dextran sulfate sodium (DSS)-induced in mice. Animals were treated orally with vehicle (water), 5-aminosalicylic acid (100 mg/kg) or methanolic extract from leaves of R. imperialis (MERI, 100 mg/kg), once a day during seven days. The disease activity index (DAI) was observed daily. Colons were collected for histological, histochemical and biochemical analysis. The administration of MERI exacerbated colitis, as indicated by DAI heightened weight loss and increased histological colonic injury. MERI also decreased the colon mucin levels and increased colonic TNF content. The colonic levels of reduced glutathione and the superoxide dismutase activity in colitic group treated with MERI were decreased. Despite the worsening of colitis, MERI not altered the intestinal transit, body weight, colon length or organs weight in normal mice. Tormentic acid (TA) and 2ß,3ß,19α-trihydroxyursolic acid (THA), compounds isolated from MERI, reduced the L929 cells viability. Thus, MERI may have aggravated the DSS-induced colitis through intense intestinal mucus barrier impairment, which would lead to inflammatory responses, TA and THA contribute to the intestinal damage verified suggesting caution about the use of R. imperialis preparations, particularly in inflammatory bowel diseases.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Rubus/química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Antioxidantes/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/imunologia , Colo/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Metanol/química , Camundongos , Mucinas/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Folhas de Planta/química , Índice de Gravidade de DoençaRESUMO
The triterpenes friedelin (1), ß-friedelinol (2) and 3,15-dioxo-21α-hydroxyfriedelane (3) in the aerial parts of Maytenus robusta, a Brazilian medicinal plant with antiulcer potential, were seasonally quantified by gas chromatography flame-ionization detection (GC-FID) using an external standard. The method was found to be linear, precise and sensitive. Compounds 1 and 2 were found in M. robusta leaves and branches, with highest concentrations in the leaves collected in autumn, i.e. 3.21 ± 0.16 and 12.60 ± 1.49 mg g-1 dry weight of 1 and 2, respectively. On the other hand, compound 3 was found only in the branches, with the highest concentrations in winter and autumn (0.21 ± 0.01 and 0.20 ± 0.02 mg g-1). The results allow to define the optimal season and plant parts for the collection of M. robusta as a phytotherapeutic drug.
Assuntos
Cromatografia Gasosa/métodos , Maytenus/metabolismo , Estações do Ano , Estômago/efeitos dos fármacos , Terpenos/farmacologia , Limite de Detecção , Padrões de ReferênciaRESUMO
Here, we evaluate the anti-inflammatory and wound-healing effects of methanolic crude extract obtained from aerial parts (leaves and branches) of Rubus imperialis Chum. Schl. (Rosaceae) and the pure compound niga-ichigoside F1. Anti-inflammatory activity was determined in vivo and in vitro, and the healing effect was evaluated in surgical lesions in mice skin. The 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay and H2O2-induced oxidative stress were used to determine antioxidant activity. The efferocytosis activity was also determined. The data obtained show that the extract of R. imperialis promote reduction in the inflammatory process induced by lipopolysaccharide (LPS) or carrageenan in the air pouch model; the effects could be reinforced by nitric oxide reduction in LPS-stimulated neutrophils, and an increase in the efferocytosis. The extract showed wound healing property in vitro and in vivo, scavenging activity for DPPH, and cytoprotection in the H2O2-induced oxidative stress in L929 cells. In addition, the compound niga-ichigoside F1 was able to reduce the NO secretion; however, it did not present wound-healing activity in vitro. Together, the data obtained point out the modulatory actions of R. imperialis extract on leukocyte migration to the inflamed tissue, the antioxidant, and the pro-resolutive activity. However, the R. imperialis anti-inflammatory activity may be mediated in parts by niga-ichigoside F1, and on wound healing do not correlated with niga-ichigoside F1.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Inflamação/prevenção & controle , Extratos Vegetais/farmacologia , Rubus , Saponinas/farmacologia , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Ferimentos Penetrantes/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/química , Carragenina , Linhagem Celular , Quimiotaxia de Leucócito/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Masculino , Metanol/química , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Picratos/química , Componentes Aéreos da Planta , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Rubus/química , Saponinas/química , Saponinas/isolamento & purificação , Pele/lesões , Pele/metabolismo , Pele/patologia , Solventes/química , Ferimentos Penetrantes/metabolismo , Ferimentos Penetrantes/patologiaRESUMO
Natural products are considered important sources of potential chemotherapeutic agents. Here, we evaluated the antiproliferative activity and the toxicological effects of the methanolic extract and a pure compound obtained from Solanum capsicoides seeds. The phytochemical profile was analyzed by chromatographic and spectroscopy methods. The acute toxicity was assessed in mice orally treated with the extract (2000 mg/kg), in vitro hemolytic activity and micronucleus test. The mutagenicity, developmental toxicity, and lethal dose (LD50) of carpesterol were estimated by the Toxicity Estimation Software Tool (TEST) software. A sulforhodamine B assay was employed to evaluate the antiproliferative activity. The toxicological assays did not observe signs of toxicity, either during the behavioral observations or in the autopsies, as well as no mutagenicity and hemolytic activity. The carpesterol did not present mutagenic effect and hemolytic activity but presents developmental toxicology and LD50 of 410 mg/kg in toxicity estimations by the TEST software. The S. capsicoides extract exhibited antiproliferative activity mainly in leukemia (K562) cell lineage. However, carpesterol presented antiproliferative activity in glioma (U251), breast (MCF-7), kidney (786-0), ovary (OVCAR-03), and K562 cell lineages. The data obtained show that S. capsicoides extract presents antiproliferative and does not present toxicological effects. In addition, it was shown for the first time the antiproliferative and toxicological parameters of carpesterol.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Metanol/química , Neoplasias/tratamento farmacológico , Fitosteróis/farmacologia , Extratos Vegetais/farmacologia , Sementes , Solanum , Solventes/química , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Feminino , Hemólise/efeitos dos fármacos , Humanos , Células K562 , Dose Letal Mediana , Células MCF-7 , Camundongos , Testes para Micronúcleos , Neoplasias/patologia , Fitosteróis/isolamento & purificação , Fitosteróis/toxicidade , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Plantas Medicinais , Sementes/química , Solanum/químicaRESUMO
The present work evaluated the chemical composition and antiulcerogenic potential of the crude extract, fractions and pure compounds isolated of roots barks from Maytenus robusta Reiss, using different pharmacological models in mice. 3,12-Dioxofriedelane (1) and 11-hydroxylup-20 (29)-en-3-one (2) were isolated from the n-hexane fraction, and mayteine (3) and 3,7-dioxofriedelane (4) from the dichloromethane fraction. The crude extract (50, 259, 500 mg/kg), all the fractions (250 mg/kg) and cimetidine (100 mg/kg) significantly reduced the lesion index, total lesion area, and percentage of lesions, in comparison with the control group (p < 0.05), by ethanol and NSAID-induced ulcer models. All the isolated compounds also presented significant pharmacological effects at 30 mg/kg. These results show that the root bark of M. robusta may be a promising source of molecules with applicability in the treatment of gastric disorders.
Assuntos
Antiulcerosos/isolamento & purificação , Maytenus/química , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos , Casca de Planta/química , Raízes de Plantas/química , Distribuição AleatóriaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves from Vernonia condensata Baker are broadly used in folk medicine for the treatment of gastric ulcers and dyspepsia. The Brazilian Public Health System (SUS) describes this species as having the potential to serve as a new herbal product with therapeutic benefits. AIM OF THE STUDY: The purpose of the study was to evaluate the gastroprotective activity and gastric healing properties of a crude ethanolic extract from leaves of V. condensata (CEEV) in different animal models. MATERIALS AND METHODS: In order to assess the gastroprotective potential of CEEV, ulcer models were established using ethanol and indomethacin. The gastric healing effect was then evaluated in the acetic acid-induced ulcer model, where the tissue was used to assess oxidative levels (reduced glutathione and lipid hydroperoxide levels, as well as superoxide dismutase and catalase activity), inflammatory [myeloperoxidase (MPO)] parameters, and mucin content. Furthermore, the ligature pylorus model, with and without secretagogue stimuli, was employed to investigate the mechanism of action of CEEV. In addition, H(+)K(+)-ATPase activity, MPO activity, and antioxidant activity through the DPPH assay were examined through in vitro trials. Phytochemical analyses were also performed. The ethanol/HCl-induced gastric ulcer method was employed to verify the gastroprotective effect of the main compound in CEEV. RESULTS: CEEV (30 and 300mg/kg, p.o) exhibited gastroprotective activity and prevented both gastric lesions induced by ethanol or indomethacin in rats. The gastric healing effect of CEEV (300mg/kg, p.o. taken twice a day for a duration of seven days) was confirmed by examining the macroscopic and microscopic appearance of chronic gastric ulcers induced by acetic acid in rats. The restorative effect of CEEV was accompanied by a significant increase in mucin content (PAS staining) and by a reduction in oxidative stress and inflammatory parameters at the site of the ulcer. Moreover, CEEV (300mg/kg), administered via an intraduodenal route, significantly reduced the volume, pH, total acidity and pepsin activity of gastric content in the pylorus ligature model in rats. The gastric acid antisecretory effect of CEEV was maintained even in the presence of cholinergic and gastrinergic, but not histaminergic, stimuli. In vitro, CEEV (1-10µg/ml) was able to scavenge free radical DPPH, but did not promote inhibitory effects on MPO or H(+),K(+)-ATPAse activity. Phytochemical analysis of CEEV indicated that luteolin is the main compound present in the extract. However, luteolin (1, 3 and 10mg/kg, p.o or 1mg/kg, i.p.) did not promote gastroprotection against ethanol/HCl in mice. It is also important to mention that oral administration of CEEV did not produce any sign of acute toxicity in animals. CONCLUSIONS: V. condensata extract demonstrates gastroprotective effects through the inhibition of gastric secretion via cholinergic and gastrinergic pathways. Furthermore, it exhibits cytoprotective effects, involving antioxidant activity, an increase in mucin content and inhibition of neutrophil migration. Thus, this medicinal plant may be a suitable natural source for the prevention and treatment of gastric lesions.