RESUMO
OBJECTIVE: Aluminum is a widely used metal in homes and industries. Xylopia aethiopica is an important medicinal plant with antioxidant properties. The objective of this study is to investigate the ameliorative potential of Xylopia aethiopica on aluminum-induced ovarian toxicity in Wistar rat. METHODS: Twenty-five rats were randomized into five groups with five rats per group. Group 1 received only distilled water; Group 2: received 150mg/kg of aluminum chloride; Group 3: received 150mg/kg aluminum chloride with 100/kg Xylopia aethiopica seed extracts; Group 4: received 150mg/kg aluminum chloride with 50 mg/kg Xylopia aethiopica seed extracts, and Group 5: received 150mg/kg aluminum chloride with 50mg/Kg zinc sulphate. For twenty-one days, all administrations were done orally. The rats were then sacrificed following chloroform anesthesia. The ovaries were harvested for histological examination. RESULTS: The data were analyzed on IBM SPSS software version 21 and the differences in mean values were considered significant at p<0.05. Xylopia aethiopica extracts significantly (p<0.05) reversed the detrimental effects of aluminum chloride on luteinizing hormone, follicle stimulating hormone, progesterone and estradiol. The histological analysis of the ovaries showed a significant improvement in rats treated with Xylopia aethiopica extract and zinc sulphate. However, Xylopia aethiopica was more effective in a dose-dependent manner. CONCLUSIONS: This study suggests that Xylopia aethiopica has ameliorative potential on aluminum-induced toxicity in the ovaries of adult female Wistar Rats.
Assuntos
Ovário , Extratos Vegetais , Ratos Wistar , Xylopia , Animais , Feminino , Extratos Vegetais/farmacologia , Ratos , Ovário/efeitos dos fármacos , Ovário/patologia , Xylopia/química , Cloreto de Alumínio/toxicidade , Estradiol , Alumínio/toxicidade , Hormônio Foliculoestimulante/sangueRESUMO
Xylopia benthamii (Annonaceae) is a plant with limited phytochemical and pharmacological evidence. Thus, using LC-MS/MS, we performed exploratory analyses of the fruit extract of X. benthamii, resulting in the tentative identification of alkaloids (1-7) and diterpenes (8-13). Through the application of chromatography techniques with the extract of X. benthamii, two kaurane diterpenes were isolated, xylopinic acid (9) and ent-15-oxo-kaur-16-en-19-oic acid (11). Their structures were established using spectroscopy (NMR 1D/2D) and mass spectrometry. The isolated compounds were submitted to anti-biofilm analysis against Acinetobacter baumannii, anti-neuroinflammatory and cytotoxic activity in BV-2 cells. Compound 11 (201.75 µM) inhibited 35% of bacterial biofilm formation and high anti-inflammatory activity in BV-2 (IC50 = 0.78 µM). In conclusion, the results demonstrated that compound 11 was characterized for the first time with pharmacological potential in the development of new alternatives for studies with neuroinflammatory diseases.
Assuntos
Diterpenos , Xylopia , Xylopia/química , Frutas , Cromatografia Líquida , Espectrometria de Massas em Tandem , Diterpenos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
The extensive distribution of Xylopia aethiopica across the continent of Africa has firmly established its medicinal value in diverse disease management. While its phytochemistry is well established, the diversity, molecular, biochemical, and antimicrobial-biosynthetic characterizations of culturable bacterial endophytes residing in fruits of X. aethiopica have not been studied previously. Additionally, danger continues to loom the global health care and management due to antibiotic resistance; hence, the discovery of microbial natural products especially from endophytes could offer a lasting solution to the quest for novel antimicrobial compounds. In this study, we isolated two bacterial endophytes Serratia sp. XAFb12 and Pseudomonas sp. XAFb13 from fresh X. aethiopica fruit. The 16S rRNA gene sequencing, Vitex biochemical test, Gram staining, and 16S rRNA gene analysis were used to confirm their phenotypic and genotypic profiles. Phylogenetic tree analysis reveals their divergence in a separate branch, indicating their uniqueness. The crude extract of both strains showed inhibition against all tested bacterial and fungal pathogens. The minimum inhibition concentration (MIC) ranged from 2.5 to 10%. Chemical analysis of the crude extracts using gas chromatography-mass spectroscopy (GC-MS) revealed the most abundant compounds to be hydrocinnamic acid, 2-piperidinone, 5-isopropylidene-3,3-dimethyl-dihydrofuran-2-one, and diethyl trisulfide. The bacterial endophytes linked to X. aethiopica were described in this study for the first time in relation to clinically significant pathogens. Our findings imply that crude extracts of the endophytic bacteria from X. aethiopica could be potentially employed as antibiotics. Hence, it is crucial to characterize the active ingredient in further detail for future pharmaceutical applications.
Assuntos
Xylopia , Xylopia/química , Filogenia , RNA Ribossômico 16S/genética , Pseudomonas/genética , Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , EndófitosRESUMO
The essential oils (EOs) of Guatteria schomburgkiana (Gsch) and Xylopia frutescens (Xfru) (Annonaceae) were obtained by hydrodistillation, and their chemical composition was evaluated by gas chromatography-mass spectrometry (GC/MS). Herbicide activity was measured by analyzing the seed germination percentage and root and hypocotyl elongation of two invasive species: Mimosa pudica and Senna obtusifolia. The highest yield was obtained for the EO of Xfru (1.06%). The chemical composition of Gsch was characterized by the presence of the oxygenated sesquiterpenes spathulenol (22.40%) and caryophyllene oxide (14.70%). Regarding the EO of Xfru, the hydrocarbon monoterpenes α-pinene (35.73%) and ß-pinene (18.90%) were the components identified with the highest concentrations. The germination of seeds of S. obtusifolia (13.33 ± 5.77%) showed higher resistance than that of seeds of M. pudica (86.67 ± 5.77%). S. obtusifolia was also more sensitive to the EO of Xfru in terms of radicle (55.22 ± 2.72%) and hypocotyl (71.12 ± 3.80%) elongation, while M. pudica showed greater sensitivity to the EO of Gsch. To screen the herbicidal activity, the molecular docking study of the major and potent compounds was performed against 4-hydroxyphenylpyruvate dioxygenase (HPPD) protein. Results showed good binding affinities and attributed the strongest inhibitory activity to δ-cadinene for the target protein. This work contributes to the study of the herbicidal properties of the EOs of species of Annonaceae from the Amazon region.
Assuntos
Annonaceae , Guatteria , Óleos Voláteis , Xylopia , Annonaceae/química , Xylopia/química , Guatteria/química , Óleos Voláteis/química , Brasil , Simulação de Acoplamento Molecular , Folhas de Planta/químicaRESUMO
Hydro-distilled essential oil from leaves of Xylopia laevigata was characterized by GC-MS. Twenty-seven components were identified and the oil's major constituents comprised germacrene D, bicyclogermacrene, (E)-caryophyllene and germacrene B. The cytotoxicity of the essential oil of X. laevigata (EOXL), determined by MTT and mitotic index methods in cultured human lymphocytes was observed in all tested concentrations. Cultures treated with EOXL demonstrated significant increase in the frequencies of micronuclei in the cytokinesis-block micronucleus assay (CBMN) and reduction of the cytokinesis-block proliferation index (CBPI) rates. Results demonstrated the cytostatic and mutagenic effects of EOXL, the latter for the first time.
Assuntos
Citostáticos/farmacologia , Linfócitos/efeitos dos fármacos , Mutagênicos/farmacologia , Óleos Voláteis/farmacologia , Xylopia/química , Células Cultivadas , Citostáticos/química , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Linfócitos/fisiologia , Testes para Micronúcleos , Mutagênicos/química , Óleos Voláteis/química , Óleos Voláteis/toxicidade , Folhas de Planta/química , Plantas Medicinais/química , Sesquiterpenos Policíclicos/análise , Sesquiterpenos de Germacrano/análiseRESUMO
Aiming to investigate the antiplasmodial activity and the phytochemical composition of Xylopia sericea leaves, the essential oil and dichloromethane extract were analyzed by gas and liquid chromatography, respectively, both of them coupled to mass spectrometry, and were evaluated against the chloroquine-resistant Plasmodium falciparum strain (W2) and for cytotoxicity to HepG2 cells. Low growth inhibition of P. falciparum as well as low cytotoxicity to HepG2 cells were observed for the essential oil. The leaves dichloromethane extract showed moderate growth inhibition of P. falciparum and low cytotoxicity to HepG2 cells. Bioguided chromatographic fractionation of this extract led to fractions with increased antiplasmodial activity from which liriodenine (IC50 6.1 ± 0.1 µg/mL, CC50 > 1000.0 µg/mL, SI > 164), an aporphine alkaloid, and an acetogenin-rich fraction containing mainly isomers of annomontacin and 4-deoxy-annomontacin (IC50 22.7 ± 1.9 µg/mL, CC50 336.1 ± 15.5 µg/mL, SI = 15) might be highlighted for their antiplasmodial activity.
Assuntos
Antimaláricos/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Xylopia/química , Animais , Antimaláricos/química , Antimaláricos/toxicidade , Aporfinas/química , Aporfinas/farmacologia , Cloroquina/farmacologia , Cromatografia Gasosa , Cromatografia Líquida , Avaliação Pré-Clínica de Medicamentos , Resistência Microbiana a Medicamentos , Furanos/farmacologia , Células Hep G2 , Humanos , Lactonas/farmacologia , Óleos Voláteis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/químicaRESUMO
Bioguided fractionation of Xylopia sericea antiplasmodial dichloromethane leaves extract led to the isolation of (-)-7-oxo-ent-kaur-16-en-19-oic acid (C20 H28 O3 ) that was identified by a combination of 1D and 2D NMR experiments (COSY, HMBC, HSQC, HSQC-TOCSY, HSQC-NOESY and NOESY) and by X-ray crystallography. A feature to be pointed out is its (4R) configuration that was inferred from the NOE experiments (HSQC-NOESY and NOESY) and X-ray crystallography. In vitro evaluation of this rare diterpene acid against the chloroquine-resistant strain Plasmodium falciparum W2 by the PfLDH method showed it disclosed a low antiplasmodial activity and was not cytotoxic to HepG2 cells (CC50 862.6±6.7â µm) by the MTT assay. The unequivocal NMR signals assignments, the X-ray crystallographic structure, the assessment to the bioactivities and the occurrence this diterpene in X. sericea are reported here for the first time.
Assuntos
Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Diterpenos do Tipo Caurano/farmacologia , Diterpenos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plasmodium falciparum/efeitos dos fármacos , Xylopia/química , Antimaláricos/química , Antimaláricos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/química , Diterpenos/isolamento & purificação , Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
BACKGROUND: This work describes a chemical study of the essential oil from leaves of Xylopia ochrantha, an endemic Annonaceae species from Brazil, and its activity against Biomphalaria species. Considering its poor solubility in aqueous medium, the essential oil was nanoemulsified to evaluate its action on controlling some mollusc species of genus Biomphalaria, snail hosts of Schistosoma mansoni that causes schistosomiasis, which mainly affects tropical and subtropical countries. OBJECTIVES: The main aims of this work were to analyse the chemical composition of essential oil from X. ochrantha, and to evaluate the effect of its nanoemulsion on molluscs of genus Biomphalaria and their oviposition. METHODS: Chemical analysis was performed by gas chromatography coupled to mass spectrometry. Nanoemulsions were prepared by a low energy method and characterised by particle size and polydispersity index. Biological assays evaluating the mortality of adult species of B. glabrata, B. straminea and B. tenagophila and their ovipositions upon contact with the most stable nanoemulsion during 24 and 48 h were performed. FINDINGS: Chemical analysis by mass spectrometry revealed the majority presence of bicyclogermacrene and germacrene D in the essential oil. The formulation with a hydrophilic-lipophilic balance (HLB) of 9.26 was the most suitable for the oil delivery system. This nanoemulsion caused the mortality in B. tenagophila, B. straminea and B. glabarata of different sizes at levels ranging from 50 to 100% in 48 h. Additionally, the formulation could inhibit the development of deposited eggs. CONCLUSION: Thus, these results suggest the use of nanoemulsified essential oil from X. ochrantha as a possible alternative in controlling some Biomphalaria species involved in the schistosomiasis cycle.
Assuntos
Biomphalaria/efeitos dos fármacos , Vetores de Doenças , Óleos Voláteis/farmacologia , Oviposição/efeitos dos fármacos , Xylopia/química , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Óleos Voláteis/isolamento & purificação , Esquistossomose mansoni/transmissãoRESUMO
OBJECTIVES: To assess the antiplasmodial activity of the ethanol extract of Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to perform a bioguided isolation of active compounds. METHODS: Dereplication of ethanol extract by the UPLC-DAD-ESI-MS/MS technique allowed the identification of the major constituents, isolation and identification of alkaloids. The antiplasmodial and cytotoxic activity of the extract, fractions and isolated compounds was evaluated against the chloroquine-resistant W2 strain Plasmodium falciparum and HepG2 cells, respectively. KEY FINDINGS: Ethanol extract showed high reduction of parasitemia as well as moderate cytotoxicity (86.5 ± 3.0% growth inhibition at 50 µg/ml and CC50 72.1 ± 5.1 µg/ml, respectively). A total of eight flavonoids were identified, and two aporphine alkaloids, anonaine and O-methylmoschatoline, were isolated. Anonaine disclosed significant antiplasmodial effect and moderate cytotoxicity (IC50 23.2 ± 2.7 µg/ml, CC50 38.3 ± 2.3 µg/ml, SI 1.6) while O-methylmoschatoline was not active against P. falciparum and showed a low cytotoxicity (33.5 ± 1.9% growth inhibition at 50 µg/ml, CC50 274.4 ± 0.5 µg/ml). CONCLUSIONS: Characterization of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS as well as its antiplasmodial activity and the occurrence of anonaine and O-methylmoschatoline in this Xylopia species are reported by the first time.
Assuntos
Alcaloides/farmacologia , Antimaláricos/farmacologia , Extratos Vegetais/farmacologia , Xylopia/química , Alcaloides/isolamento & purificação , Alcaloides/toxicidade , Antimaláricos/isolamento & purificação , Antimaláricos/toxicidade , Aporfinas/isolamento & purificação , Aporfinas/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Dioxóis/isolamento & purificação , Dioxóis/farmacologia , Etanol/química , Células Hep G2 , Humanos , Concentração Inibidora 50 , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Folhas de Planta , Plasmodium falciparum/efeitos dos fármacos , Espectrometria de Massas em Tandem/métodosRESUMO
Trachyloban-19-oic acid (1) is a diterpene very abundant in nature and its structural modification can furnish new bioactive compounds. Biotransformation of 1 by fungus Syncephalastrum racemosum provided three derivatives, two hydroxylated products (2-3) and one product of rearrangement (4). Products 3 and 4 have never been reported so far, to the best of our knowledge. Structure of 3 was formed after oxidation and rearrangement of compound 2. Compounds 1-4 were evaluated for inhibition of acetylcholinesterase, enzyme linked to the symptomatic control of Alzheimer's disease. All the compounds presented inhibitory activity higher than starting material 1, and product 3 presented IC50â¯=â¯0.06⯵M, which is about six times higher than activity found for galanthamine (IC50â¯=â¯0.38⯵M), the positive control used in this assay.
Assuntos
Inibidores da Colinesterase/química , Diterpenos/química , Diterpenos/metabolismo , Mucorales/metabolismo , Acetilcolinesterase/metabolismo , Animais , Biotransformação , Electrophorus , Ensaios Enzimáticos , Frutas/química , Estrutura Molecular , Oxirredução , Xylopia/químicaRESUMO
Brazil has the greatest vegetal biodiversity in the world, but products derived from native species are not optimally utilized. Oxalis cordata and Xylopia aromatica are two underutilized species whose leaves and fruits, respectively, have been used as food in the 19th century. In this study, we used chemical and in vitro assays to evaluate the potential of these species as functional foods. The inhibitory activity on pancreatic lipase and DPP-IV were evaluated using the crude extracts and fractions ethyl acetate, butanol and water of these two species. For polyphenols determination, samples were prepared with different solvents and these were analysed by chromatographic and spectroscopic methods. Finally, fatty acids profile was determinated by gas chromatography. The crude extract (IC50=0.84mg/ml), ethyl acetate extract (IC50=0.88mg/ml) an aqueous fraction (IC50=0.63mg/ml) of C. cordata were inhibitory on pancreatic lipase but inactive against dipeptidyl peptidase IV (DPP-IV). Extracts from X. aromatica were inactive against the lipase pancreatic enzyme, but a butanolic fraction inhibited DPP-IV (IC50=0.71±0.05mg/ml). The phenolic acids orientin/isorientin, chlorogenic acid (0.32g/100g) and the flavonoid derivatives rutin (0.27g/100g), quercetin and luteolin were observed in all products. Additionally, fatty acid quantification showed that oleic (7.5g/100g) and linoleic acid (6.5g/100g) were predominant in X. aromatica fruit. This study confirms the potential for the use of both plants as functional foods due to their nutritional value, biological activity and important phytochemical content.
Assuntos
Fármacos Antiobesidade/farmacologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Alimento Funcional/análise , Lipase/antagonistas & inibidores , Valor Nutritivo , Oxalidaceae/química , Pâncreas/enzimologia , Xylopia/química , Fármacos Antiobesidade/química , Fármacos Antiobesidade/isolamento & purificação , Brasil , Inibidores da Dipeptidil Peptidase IV/química , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Frutas/química , Pradaria , Lipase/isolamento & purificação , Lipase/metabolismo , Folhas de Planta/química , Solventes/químicaRESUMO
OBJECTIVES: The aims of this study were to investigate the chemical composition and the antioxidant activity and antibacterial activity of the essential oil of Xylopia sericea fruits (OXS). The fruits of this species are popularly used for medicinal purposes, and as a condiment in food preparation. METHODS: The chemical composition of OXS was analysed by GC/MS. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging, ß-carotene/linoleic acid bleaching and phosphomolybdenum and thiobarbituric acid-reactive substance (TBARS) assays were used to evaluate the antioxidant activity. Antibacterial activity was assessed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against bacterial strains of interest to human health and food spoilage. KEY FINDINGS: Eighty-four compounds were identified. The sesquiterpenes spathulenol (16.42%), guaiol (13.93%) and germacrene D (8.11%) were the most abundant constituents. OXS presented a significant antioxidant activity and also a high bacteriostatic effect against Staphylococcus aureus, Enterobacter cloacae, Bacillus cereus and Klebsiella pneumoniae. CONCLUSIONS: Those results evidenced the potential of OXS to treat human bacterial infections and as an antimicrobial ingredient for food preservation.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Frutas/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Xylopia/química , Antibacterianos/química , Antioxidantes/química , Bactérias/efeitos dos fármacos , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Brasil , Testes de Sensibilidade Microbiana/métodos , Óleos Voláteis/química , Picratos/química , Picratos/farmacologia , Extratos Vegetais/química , Óleos de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de GuaianoRESUMO
Xylopia laevigata (Annonaceae), known locally as "meiú" or "pindaíba", is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (-)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (-)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (-)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G2/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids.
Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Aporfinas/farmacologia , Citotoxinas/farmacologia , Caules de Planta/química , Xylopia/química , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Aporfinas/química , Aporfinas/isolamento & purificação , Citotoxinas/química , Citotoxinas/isolamento & purificação , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células HL-60 , Células Hep G2 , Humanos , Células K562 , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Camundongos , Extratos Vegetais/química , Cultura Primária de CélulasRESUMO
Gastrointestinal pathology in diabetic patients has become a source of concern in recent times. The aim of this study was to investigate the ultrastructural and immunohistochemical effects of aqueous leaf extract of Xylopia aethiopica on the stomach in streptozotocin-induced diabetic rats. This study was conducted using thirty adult Wistar rats. The animals were divided into three groups (n= 10). Group A was the control animals (administered with equivalent volume of citrate buffer), group B was diabetic animals induced by a single intraperitoneal injection of streptozotocin dissolved in citrate buffer (65 mg/kg) and group C was diabetic animals treated with 200 mg/kg body weight of aqueous leave extract of X. aethiopica for twenty five days. At the expiration of the study, all the animals in each of the groups were sacrificed and the stomach excised and fixed in both 10 % formol and karnovsky fixatives immunohistochemical, light microscopic and electron microscopic studies respectively. The results showed a gradual decline (P<0.05) in the blood glucose level in the extract treated group as against the increment in untreated diabetic group. There was a distortion of the glandular mucosa and epithelium in the untreated diabetic group vis-à-vis the extract treated and control groups. The immunohistochemical staining and percentage immunoreactivity of the stomach of untreated diabetic group showed that the immunoexpression of H+/K+-ATPase were sparse and significantly (p<0.000) lower compared with the control group. There was a better staining pattern for H+/K+-ATPase gastric proton pump in the group treated with aqueous leaf extract of X. aethiopica as compared with the untreated diabetic group. The ultrastructural studies of untreated diabetic group revealed a reduction in the density of mitochondria as compared with the control group. Treatment with leaf extract of X. aethiopica increased the mitochondrial density as well as uniform dispersal of chromatin. It is concluded that diabetes causes gastric pathology thus resulting in morphological changes in the gastric histo-architecture and parietal cells. The aqueous leaf extract of X. aethiopica enhances the recovery/restoration of these defects in streptozotocin induced diabetic rats and as such, may play a significant role in the management of complications associated with diabetes mellitus.
La enfermedad gastrointestinal en pacientes diabéticos se ha convertido en una fuente de preocupación en los últimos tiempos. El objetivo fue investigar los efectos ultraestructurales e inmunohistoquímicos de extracto acuoso de la hoja de Xylopia aethiopica en el estómago de ratas con diabetes inducida por estreptozotocina. Se utilizaron 30 ratas Wistar adultas, divididas en tres grupos (n= 10). El Grupo A, control (se le administró un volumen equivalente de tampón de citrato); el Grupo B, animales diabéticos inducidos por una sola inyección intraperitoneal de estreptozotocina disuelta en tampón de citrato (65 mg/kg) y el Grupo C, animales diabéticos con 200 mg/kg peso corporal tratados con extracto acuoso de X. aethiopica durante 25 d. Luego, todos los animales fueron sacrificados, se les extirpó el estómago y fijó en formol al 10 % y en fijador Karnovsky para anticuerpos monoclonales contra la bomba de protones gátrica H+/K+-ATPasa; las muestras se observaron mediante microscopías óptica y electrónica. Los resultados mostraron una disminución gradual (P<0,05) en el nivel de glucosa en sangre del grupo tratado con el extracto, contra un incremento en el grupo diabético no tratado. Hubo una distorsión de la mucosa glandular y el epitelio en el grupo diabético no tratado vis-à-vis los grupos tratados con extracto y el de control. La tinción inmunohistoquímica del estómago del grupo diabético no tratado, mostró escasas células parietales inmunorreactivas en el grupo diabético no tratado comparado con el grupo control. Hubo un mejor patrón de tinción en la bomba de protones gátrica H+/K+-ATPasa en el grupo tratado con el extracto de hoja acuosa de X. aethiopica, en comparación con el grupo diabético no tratado. Los estudios ultraestructurales del grupo diabético no tratado revelaron una reducción en la densidad de las mitocondrias en comparación con el grupo control. El tratamiento con extracto de hoja de X. aethiopica aumentó la densidad mitocondrial, así como la dispersión uniforme de la cromatina. Se concluye que la diabetes causa una enfermedad gástrica que genera cambios morfológicos en la histoarquitectura de las células parietales gástricas. El extracto de hoja acuosa de X. aethiopica mejora la recuperación/restauración de estos defectos en ratas diabéticas inducidas por estreptozotocina y, como tal, puede jugar un rol significativo en el tratamiento de las complicaciones asociadas con la diabetes mellitus.
Assuntos
Animais , Masculino , Ratos , Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Estômago/efeitos dos fármacos , Xylopia/química , Imuno-Histoquímica , Microscopia Eletrônica , Ratos Wistar , Estômago/ultraestruturaRESUMO
BACKGROUND: Xylopia frutescens Aubl. (embira, semente-de-embira or embira-vermelha), is used in folk medicine as antidiarrheal. The essential oil from its leaves (XF-EO) has been found to cause smooth muscle relaxation. Thus, the aim of this study was to investigate the spasmolytic action by which XF-EO acts on guinea pig ileum. METHODS: The components of the XF-EO were identified by gas chromatography-mass spectrometry. Segments of guinea pig ileum were suspended in organ bath containing modified Krebs solution at 37 °C, bubbled with carbogen mixture under a resting tension of 1 g. Isotonic contractions were registered using kymographs and isometric contractions using force transducer coupled to an amplifier and computer. Fluorescence measurements were obtained with a microplate reader using Fluo-4. RESULTS: Forty-three constituents were identified in XF-EO, mostly mono- and sesquiterpenes. XF-EO has been found to cause relaxation on guinea pig ileum. The essential oil inhibited in a concentration-dependent manner both CCh- and histamine-induced phasic contractions, being more potent on histamine-induced contractions as well as antagonized histamine-induced cumulative contractions in a non-competitive antagonism profile. XF-EO relaxed in a concentration-dependent manner the ileum pre-contracted with KCl and histamine. Since the potency was smaller in organ pre-contracted with KCl, it was hypothesized that XF-OE would be acting as a K(+) channel positive modulator. In the presence of CsCl (non-selective K(+) channel blocker), the relaxant potency of XF-OE was not altered, indicating a non-participation of these channels. Moreover, XF-EO inhibited CaCl2-induced cumulative contractions in a depolarizing medium nominally without Ca(2+) and relaxed the ileum pre-contracted with S-(-)-Bay K8644 in a concentration-dependent manner, thus, was confirmed the inhibition of Ca(2+) influx through Cav1 by XF-EO. In cellular experiments, the viability of longitudinal layer myocytes from guinea pig ileum was not altered in the presence of XF-OE and the Fluo-4-associated fluorescence intensity in these intestinal myocytes stimulated by histamine was reduced by the essential oil, indicating a [Ca(2+)]c reduction. CONCLUSION: Spasmolytic action mechanism of XF-EO on guinea pig ileum can involve histaminergic receptor antagonism and Ca(2+) influx blockade, which results in [Ca(2+)]c reduction leading to smooth muscle relaxation.
Assuntos
Cálcio/análise , Íleo/efeitos dos fármacos , Óleos Voláteis/farmacologia , Parassimpatolíticos/farmacologia , Óleos de Plantas/farmacologia , Xylopia/química , Animais , CobaiasRESUMO
Xylopia langsdorfiana A. St.-Hil. &Tul. (Annonaceae) is popularly known in the northeast of Brazil as 'pimenteira da terra', and an essential oil (XL-OE) was extracted from its leaves. Since Xylopia species are cited in folk medicine and diterpenes from X. langsdorfiana have spasmolytic activity, this study aimed to investigate a possible spasmolytic action of XL-OE on smooth muscle models. XL-OE (243 and 729 µg/mL) showed low pharmacologic efficacy on guinea pig trachea and rat aorta and uterus. However, in guinea pig ileum, XL-OE (27-729 µg/mL) inhibited carbachol or histamine-induced phasic contractions (1 µM) in a significant and concentration-dependent manner. In addition, XL-OE (81 µg/mL) reduced fluorescence intensity in ileal myocytes stimulated by histamine, indicating a decrease in cytosolic calcium concentration, which could explain the spasmolytic activity. Thus, XL-OE proved to be a promising natural product to be used in gastrointestinal diseases acting by modulating the cytosolic calcium concentration.
Assuntos
Óleos Voláteis/química , Parassimpatolíticos/química , Óleos de Plantas/química , Xylopia/química , Animais , Aorta/efeitos dos fármacos , Cálcio/química , Citosol/química , Diterpenos/química , Feminino , Cobaias , Íleo/efeitos dos fármacos , Células Musculares/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Folhas de Planta/química , Ratos , Traqueia/efeitos dos fármacos , Útero/efeitos dos fármacosRESUMO
Xylopia laevigata (Annonaceae) is a medicinal plant used in folk medicine to treat pain and inflammation. Thus, we investigated the possible antioxidant, antinociceptive, and anti-inflammatory effects of X. laevigata leaf essential oil (EOX) in animal models. Our EOX sample showed the presence of γ-muurolene (17.78%), δ-cadinene (12.23%), bicyclogermacrene (7.77%), and α-copaene (7.17%) as main compounds. EOX presented a strong antioxidant potential according to the DPPH, TBARS, and nitrite production tests. Additionally, pretreatment with EOX, in mice, also significantly produced (P < 0.05 or P < 0.001) antinociceptive effect by reduction of nociceptive behavior (in formalin and writhing tests). The EOX showed c-Fos label in the olfactory bulb, piriform cortex, and periaqueductal gray. Acute administration of EOX exhibited a significant (P < 0.01 or P < 0.001) anti-inflammatory profile in the carrageenan-induced peritonitis and by the carrageenan-induced hindpaw edema tests in mice. Our results provide evidence for the use of X. laevigata by traditional medicine practitioners in the management of pain and inflammatory disorders.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Xylopia/química , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/uso terapêutico , Peritonite/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Sesquiterpenos/análiseAssuntos
Xylopia/química , Xylopia/metabolismo , Alcaloides/análise , Alcaloides/metabolismo , Benzoatos/análise , Benzoatos/metabolismo , Metabolismo dos Carboidratos , Carboidratos/análise , Clorofila/análise , Clorofila/metabolismo , Flavonoides/análise , Flavonoides/metabolismo , Lignanas/análise , Lignanas/metabolismo , Terpenos/análise , Terpenos/metabolismo , Xantenos/análise , Xantenos/metabolismoRESUMO
Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca(2+)-calmodulin complex was eliminated as chlorpromazine (10(-6) M), a calmodulin inhibitor, did not significantly alter the diterpene-induced relaxation (pD2 = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD2 = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K(+) channels. This was confirmed, as in the presence of 10 mM TEA(+) (a non-selective K(+) channel blocker), diterpene relaxation potency was significantly reduced (pD2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K(+) channel subtypes KATP, KV, SKCa and BKCa seem to be modulated positively by trachylobane-318 (pD2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the Kir subtype channel (pD2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10(-5) M trachylobane-318 (pD2 = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K(+) channels, particularly the KATP, KV, SKCa and BKCa subtypes.
Assuntos
Diterpenos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Xylopia/química , Animais , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Cobaias , Técnicas In Vitro , Masculino , Canais de Potássio/classificação , Canais de Potássio/metabolismoRESUMO
The aim of this study was to investigate the chemical composition and anticancer effect of the leaf essential oil of Xylopia frutescens in experimental models. The chemical composition of the essential oil was analysed by GC/FID and GC/MS. In vitro cytotoxic activity of the essential oil was determined on cultured tumour cells. In vivo antitumour activity was assessed in Sarcoma 180-bearing mice. The major compounds identified were (E)-caryophyllene (31.48%), bicyclogermacrene (15.13%), germacrene D (9.66%), δ-cadinene (5.44%), viridiflorene (5.09%) and α-copaene (4.35%). In vitro study of the essential oil displayed cytotoxicity on tumour cell lines and showed IC50 values ranging from 24.6 to 40.0 µg/ml for the NCI-H358M and PC-3M cell lines, respectively. In the in vivo antitumour study, tumour growth inhibition rates were 31.0-37.5%. In summary, the essential oil was dominated by sesquiterpene constituents and has some interesting anticancer activity.