RESUMEN
OBJECTIVES: To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. METHODS: Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. KEY FINDINGS: Treatment of CIA mice with HCE 5 mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. CONCLUSIONS: HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.
Asunto(s)
Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Chenopodium ambrosioides/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Animales , Antiinflamatorios/aislamiento & purificación , Artritis Experimental/inmunología , Artritis Experimental/patología , Densidad Ósea/efectos de los fármacos , Interleucina-6/sangre , Masculino , Ratones Endogámicos DBA , Rótula/efectos de los fármacos , Rótula/patología , Extractos Vegetales/aislamiento & purificación , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVES: To evaluate the anti-inflammatory potential of Pterodon polygalaeflorus hexane extract (HE) and its fractions on macrophage migration in vitro and in vivo. METHODS: Hexane extract from P. polygalaeflorus fruits was fractionated and yielded four fractions. RAW 264.7 cells were treated with samples to evaluate cell viability (MTT assay), cell migration (wound healing and transwell assays), CD14 expression (flow cytometry), iNOS and cytokine mRNA expression (RT-qPCR), NO (Griess reaction) and cytokine (ELISA) production. In vivo migration was evaluated on the thioglycollate-induced peritonitis model. Qualitative analysis was performed by GC-MS. KEY FINDINGS: All fractions inhibited the NO production by LPS-stimulated RAW 264.7 cells. Fr3 and Fr4 presented the lowest IC50 values. The expressions of iNOS and IL-1ß, TNF-α and IL-10 cytokines were inhibited by Fr3 and Fr4, whereas the CD14 expression was only inhibited by Fr3. All the samples inhibited RAW 264.7 migration in the wound healing and transwell assays. Fr3 and Fr4 reduced the migration of Mac-1+ Gr-1- cells to the peritoneum and presented in their compositions: 6α-hydroxy-7ß-acetoxyvouacapan-17ß-oate, methyl 6α,7ß-dihydroxyvouacapan-17ß-oate, methyl 6α-acetoxy-7ß-hydroxyvouacapan-17ß-oate, geranylgeraniol and 14,15-epoxy-geranylgeraniol. CONCLUSIONS: The anti-inflammatory effects of Fr3 and Fr4 involve inhibition of cell migration, iNOS expression and NO production, cytokine expression (mRNA and proteins) and CD14 expression (Fr3).
Asunto(s)
Antiinflamatorios/farmacología , Movimiento Celular/efectos de los fármacos , Citocinas/biosíntesis , Diterpenos/farmacología , Fabaceae/química , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Frutas/química , Receptores de Lipopolisacáridos/biosíntesis , Macrófagos/citología , Ratones , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Extractos Vegetales/químicaRESUMEN
Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1ß production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 µg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins.
Asunto(s)
Apigenina/farmacología , Edema/tratamiento farmacológico , Peperomia/química , Extractos Vegetales/farmacología , Enfermedad Aguda , Animales , Apigenina/química , Biomarcadores , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/etiología , Edema/metabolismo , Edema/patología , Mediadores de Inflamación/metabolismo , Estructura Molecular , Fosfolipasas A2 Secretoras/metabolismo , Extractos Vegetales/química , RatasRESUMEN
BACKGROUND & OBJECTIVES: Aedes aegypti mosquito is the principal vector of the viruses responsible for urban yellow fever, dengue, dengue haemorrhagic fever, as well as Zika and chikungunya in Brazil. The present study was aimed to investigate the insecticidal potential of the extract and fractions of Ottonia anisum, along with special metabolites isolated from it, as natural alternatives against larvae (L3) of Ae. aegypti, vector of potentially deadly tropical infections in Brazil. METHODS: The plant species O. anisum was collected in March 2015, at Xerιm area, in Rio de Janeiro City, Brazil. Crude extracts and the isolated pure compounds were screened for toxicity against Ae. aegypti larvae (L3). Bioassays were performed on 20 larvae (L3) of Ae. aegypti in triplicate. The samples were dissolved in a mixture of acetone and DMSO at final concentrations of 1-200 µg/ml. The toxicity of the solutions was evaluated towards the growth and development of Ae. aegypti larvae till emergence of adults. RESULTS: The crude hexane extract showed 100% larval mortality 24 h after treatment at a concentration of 200 µg/ml. The bioassays using 1-butyl-3,4-methylenedioxybenzene revealed 100% mortality among L3 larvae, 24 h afterthe treatment at a concentration of 30 µg/ml, the LC recorded was 1.6 µg/ml. At concentration of 10 µg/ml, the L3 larval mortality recorded was 92%. INTERPRETATION & CONCLUSION: The metabolite 1-butyl-3,4-methylenedioxybenzene showed potent toxicity against Ae. aegypti larvae. This arylbutanoid agent could be used as a natural alternative adjuvant pesticide, in new compositions that would be environmentally safer.
Asunto(s)
Aedes/efectos de los fármacos , Insecticidas/farmacología , Mosquitos Vectores , Fitoquímicos/farmacología , Piper/química , Extractos Vegetales/farmacología , Aedes/fisiología , Animales , Bioensayo , Brasil , Insecticidas/aislamiento & purificación , Larva/efectos de los fármacos , Larva/fisiología , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Análisis de SupervivenciaRESUMEN
Piperaceae species can be found worldwide in tropical and subtropical areas and many of them have been used for centuries in traditional folk medicine and in culinary. In Brazil, species of Piperaceae are commonly used in some communities as local anesthetic and analgesic. Countrified communities have known some species of the genus Ottonia as "anestesia" and it is a common habit of chewing leaves and roots of Ottonia species to relief toothache. The purpose of this study is to report our findings on new molecules entities obtained from the roots of Ottonia anisum Spreng, in which local anesthetic activity (sensory blockage) is demonstrated for the first time in vivo guinea pig model. Phytochemical investigation led to the isolation of three amides (pipercallosidine, piperine and valeramide) and in an enriched mixture of seven amides (valeramide, 4,5-dihydropiperlonguminine, N-isobutil-6-piperonil-2-hexenamide, piperovatine, dihydropipercallosidine, pipercallosidine and pipercallpsine). Our findings demonstrated the anesthetic potential for the methanolic extract from roots, its n-hexane partition and amides from O. anisum and it is in agreement with ethnobotanical survey.
Asunto(s)
Amidas/aislamiento & purificación , Anestésicos Locales/aislamiento & purificación , Piperaceae/química , Extractos Vegetales/química , Raíces de Plantas/química , Animales , Benzodioxoles/aislamiento & purificación , Brasil , Cobayas , Hexanos/aislamiento & purificaciónRESUMEN
To determine the absolute configuration of 3-ishwarone, the experimental electronic circular dichroism (ECD), electronic dissymmetry factor (EDF), optical rotatory dispersion (ORD), vibrational circular dichroism (VCD), and vibrational dissymmetry factor (VDF) spectra of (+)-3-ishwarone are analyzed with the corresponding density functional theoretical predictions for different diastereomers. ECD and ORD spectra by themselves could not facilitate the determination of the absolute configuration of this molecule. However, the magnitude of the experimental EDF of (+)-3-ishwarone is found to match better with that predicted for the (1R,2S,4S,5R,9R,11R) diastereomer. The analyses of similarity measures between experimental and predicted spectra for VCD and VDF clearly suggested that the absolute configuration of (+)-3-ishwarone is (1R,2S,4S,5R,9R,11R).
Asunto(s)
Sesquiterpenos/química , Algoritmos , Brasil , Dicroismo Circular , Estructura Molecular , Dispersión Óptica Rotatoria , Peperomia/química , Componentes Aéreos de las Plantas/química , EstereoisomerismoRESUMEN
3-Ishwarone, (1), a sesquiterpene with a rare ishwarane skeleton, was isolated from Peperomia scandens Ruiz & Pavon (Piperaceae). Its structure was unambiguously determined by 1D- and 2D-NMR and infrared analyses, as well as by comparative theoretical studies which involved calculations of 13C-NMR chemical shifts, using the Density Functional Theory (DFT) with the mPW1PW91 hybrid functional and Pople's 6-31G(d) basis set, and of vibrational frequencies, using the B3LYP hybrid functional and triple ζ Dunning's correlation consistent basis set (cc-pVTZ), of (1) and three of its possible diastereomers, compounds 2-4.
Asunto(s)
Peperomia/química , Sesquiterpenos/química , Cromatografía de Gases y Espectrometría de Masas , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
The increased life expectancy of the population has led to increasing incidences of cancer, chronic inflammatory and autoimmune diseases. Thus the continuous search for new drugs is necessary because ineffectiveness and adverse effects have been described for standard drugs. Essential oils are important sources of bioactive metabolites and several clinical trials have been developed using them. The Pterodon genus has been used in traditional medicine to treat rheumatic disorders, thus this work investigated the properties of essential oil from Pterodon polygalaeflorus fruits (EsOPpg) on acute inflammation and lymphocyte activation. The essential oil was obtained by hydrodistillation and its components were identified by GC/MS. The anti-inflammatory response was assessed using the air pouch model. Antinociceptive potential was evaluated using the writhing model. Lymphocyte phenotyping, cell cycle and apoptosis were analyzed by flow cytometry. EsOPpg promoted a reduction in leukocyte counts and protein concentration in the exudate, and reduced vasodilatation and inflammatory cell infiltrate in air pouch tissue. No antinociceptive effect was demonstrated for the doses tested. EsOPpg inhibited lymphocyte proliferation, arresting the cell cycle in G1 phase, and induced apoptosis in these cells. EsOPpg downregulated both the total number of CD8(+) T cells and the activated subpopulation (CD8(+)CD69(+)), while promoting upregulation of the total number of CD19(+) and CD19(+)CD69(+) B cells. In conclusion, Pterodon polygalaeflorus essential oil diminished the acute inflammatory response and inhibited lymphocyte proliferation, reducing neutrophil recruitment into the cavity and air pouch tissue and promoting distinct modulations of the activation level of each lymphocyte subpopulation.
Asunto(s)
Antiinflamatorios/uso terapéutico , Fabaceae/química , Inflamación/tratamiento farmacológico , Activación de Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Aceites Volátiles/uso terapéutico , Fitoterapia , Animales , Antiinflamatorios/farmacología , Antígenos CD/metabolismo , Antígenos CD19/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Apoptosis/efectos de los fármacos , Linfocitos B/metabolismo , Linfocitos T CD8-positivos/metabolismo , Ciclo Celular/efectos de los fármacos , Frutas , Inflamación/inmunología , Lectinas Tipo C/metabolismo , Recuento de Leucocitos , Masculino , Ratones , Ratones Endogámicos , Infiltración Neutrófila/efectos de los fármacos , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Linfocitos T/metabolismo , Vasodilatación/efectos de los fármacosRESUMEN
The Piperaceae species are known worldwide for its medicinal properties and its chemical compounds. In Brazil, many species of this family are distributed mainly in Amazon Region and in the Atlantic Forest. The genus Ottonia is known as source of amides, flavonoids, arilpropanoids and terpenes with record biological activities. Six aristolactams, including, aristolactam BII, piperolactam C, goniothalactam, stigmalactam, aristolactam AII and aristolactam BIII were isolated from roots of this species. GC-MS, 1H NMR and NOESY techniques were used to characterize these compounds. This is the first report about the occurrence of aristolactams in the Ottonia anisum Sprengel.
Asunto(s)
Lactamas/aislamiento & purificación , Piperaceae/química , Brasil , Cromatografía de Gases y Espectrometría de Masas , Lactamas/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Raíces de Plantas/químicaRESUMEN
Analyses of essential oils obtained from fresh and dried leaves and inflorescences of Piper clausenianum were performed using GC-FID, GC-MS and NMR techniques. Forty compounds were detected for these four oils with the total of identified constituents ranging from 88.7% for the dried inflorescences to 97.7% for the dried leaves. Sesquiterpenes were the main constituents in the volatile fraction from leaves with a high percentage of (E)-nerolidol (up to 83%). However, monoterpenes were identified in greater amount in the inflorescences, with linalool percentages from 50% up. The essential oils from fresh leaves and inflorescences were submitted to anti-parasitic activity against a strain of Leishmania amazonensis. Both samples showed biological activity, but the essential oil from P. claussenianum fresh leaves, which was rich in (E)-nerolidol, showed effective growth inhibition of L. amazonensis due to the high percentage of this metabolite in the mixture.
Asunto(s)
Aceites Volátiles/química , Piper/química , Aceites de Plantas/química , Flores/química , Leishmania/efectos de los fármacos , Hojas de la Planta/químicaRESUMEN
The methanol extract from aerial parts of the Peperomia blanda (Piperaceae) yielded two C-glycosyl-flavones. Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR, chemical transformation and comparison with the related known compounds. The structure of the new flavonoids were established as 4'-methoxy-vitexin 7-O-beta-D-xylopyranoside (1) (7-O-beta-D-xylopyranosyl-8-C-beta-D-glucopyranosyl-4'-methoxy-apigenin) and vicenin-2 (2). The antioxidant activity of both compounds was investigated using the DPPH assay. Both compounds showed only modest activity, with IC50 values of 357.2 microM for 1, and 90.5 microM for 2.
Asunto(s)
Antioxidantes/aislamiento & purificación , Apigenina/aislamiento & purificación , Flavonas/aislamiento & purificación , Glucósidos/aislamiento & purificación , Peperomia/química , Extractos Vegetales/química , Antioxidantes/química , Antioxidantes/farmacología , Apigenina/química , Apigenina/farmacología , Flavonas/química , Flavonas/farmacología , Glucósidos/química , Glucósidos/farmacología , Estructura Molecular , Componentes Aéreos de las Plantas , Extractos Vegetales/farmacologíaRESUMEN
The family Piperaceae encompasses 5 genera, Piper, Peperomia, Pothomorphe, Ottonia and Sarcorhachis, and approximately 2,000 species widely distributed in the tropical and subtropical regions of the world. Most of the Ottonia species are native to Brazil and they are used in folk medicine as diuretic, salivating, and anaesthetic. Chemical studies of non-polar fractions from leaves and roots of Ottonia anisum Sprengel lead to the isolation of an arylbutanoic metabolite, the 1-butyl-3,4-methylenedioxybezene.
A família Piperaceae é formada por 5 gêneros, Piper, Peperomia, Pothomorphe, Ottonia e Sarcorhachis, com cerca de 2000 espécies de ampla distribuição nas regiões tropicais e subtropicais do mundo. Das 23 espécies descritas para o gênero Ottonia, a maioria é nativa do Brasil. Essas plantas são popularmente utilizadas no país como diuréticas, salivantes e anestésicas. O estudo químico dos extratos apolares de folhas e de raízes de Ottonia anisum Sprengel levou aoisolamento de um componente majoritário identifi cado como o derivado arilbutanoídico: 1-butil-3,4-metilenodioxibeneno.
RESUMEN
From the methanol extract of the aerial parts of Peperomia blanda (Piperaceae), two chromenes were isolated and characterized mainly through application of 2D-NMR spectroscopy. The structures were 2S-(4-methyl-3-pentenyl)-6-formyl-8-hydroxy-2,7-dimethyl-2H-chromene and 2S-(4-methyl-3-pentenyl)-5-hydroxy-6-formyl-2,7-dimethyl-2H-chromene named as blandachromenes I and II, respectively.