RESUMO

Abstract The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5ßH-9ßH-iridoid-1α-O-(6'-O-(6,7-dihydrofoliamenthonyl)-ß-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6'-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal

Assuntos

Animais , Masculino , Feminino , Camundongos , Ratos , Lamiaceae/anatomia & histologia , Vitex/efeitos adversos , Analgésicos/classificação , Anti-Inflamatórios/classificação , Cromatografia Líquida de Alta Pressão/métodos , Folhas de Planta/efeitos adversos , Compostos Fitoquímicos

RESUMO

Abstract Adenocalymma axillarum (K.Schum.) L.G. Lohmann is a liana belonging to the family Bignoniaceae. In traditional medicine, the genus Adenocalymma is used to treat fever, skin ailments, and body, joint, and facial muscle pains, and it is also applied as cosmetic. Biological assays conducted with the A. axillarum crude leaf ethanol extract have indicated leishmanicidal activity and absence of cytotoxicity. This study aimed to analyze the A. axillarum leaf ethanol crude extract by high-performance liquid chromatography-high-resolution mass spectrometry- diode array detector (HPLC-HRMS-DAD) and to evaluate the leishmanicidal and cytotoxic activities of this crude extract, its fractions, and isolated compounds. HPLC-HRMS-DAD analysis of this extract revealed that it consisted mainly of flavonoids, with nine major compounds. Extract purification yielded 4-hydroxy-N-methylproline, 6-β-hydroxyipolamiide, quercetin-3-O-robinobioside, hyperin, isorhamnetin-3-O-robinobioside, and 3'-O-methylhyperin, which were identified by Nuclear Magnetic Resonance. The isolated compounds were inactive against Leishmania amazonensis promastigotes and human lung fibroblast cells.

Assuntos

Espectrometria de Massas/métodos , Espectroscopia de Ressonância Magnética/métodos , Cromatografia Líquida de Alta Pressão/métodos , Folhas de Planta/classificação , Misturas Complexas/química , Leishmania/classificação , Bignoniaceae/classificação , Articulações/anormalidades

RESUMO

Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl-), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.

RESUMO

Plumieride (PLU), an iridoid isolated from Allamanda cathartica flowers, has been studied by our research group due to its anti-inflammatory potential, antidepressant-like and anxiolytic-like effects. This research investigated the involvement of GABAergic and monoaminergic systems in the anxiolytic-like effect elicited by PLU. Therefore, mice were pre-treated with GABAergic, serotonergic, adrenergic or dopaminergic receptor antagonists (i.p.), and exposed to Elevated Plus-Maze (EPM) and Open-Field Test (OFT). The preliminary results revealed that PLU (p.o.) possibly interacts with the mentioned systems through the GABAA, GABAB, 5-HT1A, 5-HT3, α1, α2, and D2 receptors.

Assuntos

Ansiolíticos , Compostos de Espiro , Animais , Ansiolíticos/farmacologia , Antidepressivos , Furanos , Camundongos

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chilean population relies on medicinal plants for treating a wide range of illnesses, especially those of the gastrointestinal system. Junellia spathulata (Gillies & Hook.) Moldenke var. spathulata (Verbenaceae), called as "verbena-azul-de-cordilleira", is a medicinal plant native to Argentina and Chile traditionally used for treating digestive disorders. Although the species of the genus are important as therapeutic resources for the Andean population, the plants are very scarcely studied. AIMS OF THE STUDY: The purpose of the present study was to find out the main constituents and investigate the protective effect of J. spathulata against oxidative stress induced by the potent oxidant 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in human hepatoblastoma cells. MATERIALS AND METHODS: The crude methanol extract of J. spathulata and an iridoid obtained by chromatographic processes were tested to access the hepatoprotective effect and cytotoxicity in HepG2 cell. In addition, the reducing power of the samples and their ability to scavenge free radicals were evaluated using FRAP and ORAC assay systems. RESULTS: The iridoid asperuloside, the main compound of the crude methanol extract of J. spathulata, was isolated and identified by means of NMR analysis. The crude methanol extract of J. spathulata and asperuloside protected HepG2 cells against oxidative damage triggered by AAPH-derived free radicals. This effect can be credited to the ability of the extract and asperuloside to protect the liver cells from chemical-induced injury, which might be correlated to their free radical scavenging potential. CONCLUSIONS: This study experimentally evidenced the ethnopharmacological usefulness of J. spathulata as a treatment of digestive disorders. Our result could stimulate further investigations of hepatoprotective agents in other Chilean Junellia species.

Assuntos

Monoterpenos Ciclopentânicos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Glucosídeos/farmacologia , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Piranos/farmacologia , Verbenaceae , Sobrevivência Celular/efeitos dos fármacos , Chile , Monoterpenos Ciclopentânicos/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Glucosídeos/isolamento & purificação , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Extratos Vegetais/isolamento & purificação , Piranos/isolamento & purificação , Verbenaceae/química

RESUMO

Iridoid blue-based pigments can be found in fruits of genipap (Genipa americana L.). Besides being a potential source of natural blue colorant in the food industry, they have also been associated with pharmacological effects. Therefore, the recovery of iridoids by ultrasound-assisted extraction from both unripe and ripe fruits was analysed by UPLC-DAD-ESI-(-)-QTOF-MS/MS. Nine iridoids were identified from their exact masses and fragmentation pattern, namely geniposidic acid, gardenoside, genipin-1-ß-gentiobioside, geniposide, 6''-O-p-coumaroyl-1-ß-gentiobioside geniposidic acid, 6''-O-p-coumaroylgenipin-gentiobioside, genipin, 6'-O-p-coumaroyl-geniposidic acid and 6'-O-feruloyl-geniposidic acid. Among them, genipin (60.77 mg/g fdw) was found to be the most abundant iridoid in unripe genipap extract, while the ripe genipap extract mainly contained geniposide and geniposidic acid (89.48 and 25.04 mg/g fdw, respectively). It was also observed that the iridoids of the unripe genipap extract are able to scavenger DPPH, ABTS and peroxyl radicals as well as exerting a cytostatic effect against both glioma and breast cancer cell lines. This study provided information about the properties of unripe and ripe genipap extracts which can be used as a reference for further studies focusing on the potential application of G. americana L. in commercial products containing natural blue colorant with functional claims.

Assuntos

Antioxidantes , Frutas , Antioxidantes/farmacologia , Iridoides , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem

RESUMO

Genipap (Genipa americana L.) is a native fruit from Amazonia that contains bioactive compounds with a wide range of bioactivities. However, the response to genipap juice ingestion in the human exposome has never been studied. To identify biomarkers of genipap exposure, the untargeted metabolomics approach in human urine was applied. Urine samples from 16 healthy male volunteers, before and after drinking genipap juice, were analyzed by liquid chromatography⁻high-resolution mass spectrometry. XCMS package was used for data processing in the R environment and t-tests were applied on log-transformed and Pareto-scaled data to select the significant metabolites. The principal component analysis (PCA) score plots showed a clear distinction between experimental groups. Thirty-three metabolites were putatively annotated and the most discriminant were mainly related to the metabolic pathways of iridoids and phenolic derivatives. For the first time, the bioavailability of genipap iridoids after human consumption is reported. Dihydroxyhydrocinnamic acid, (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate, hydroxyhydrocinnamic acid, genipic acid, 12-demethylated-8-hydroxygenipinic acid, 3(7)-dehydrogenipinic acid, genipic acid glucuronide, nonate, and 3,4-dihydroxyphenylacetate may be considered biomarkers of genipap consumption. Human exposure to genipap reveals the production of derivative forms of bioactive compounds such as genipic and genipinic acid. These findings suggest that genipap consumption triggers effects on metabolic signatures.

Assuntos

Sucos de Frutas e Vegetais , Frutas , Iridoides/urina , Fenóis/urina , Rubiaceae , Administração Oral , Adolescente , Adulto , Biomarcadores/urina , Biotransformação , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Humanos , Masculino , Metabolômica/métodos , Espectrometria de Massas por Ionização por Electrospray , Urinálise , Adulto Jovem

RESUMO

ABSTRACT The phytochemical study of Galium tunetanum Lam., Rubiaceae, leaves led to the isolation of 13 compounds from the chloroform-methanol and the methanol extracts, including six iridoid glycosides, one non-glycoside iridoid, two p-coumaroyl iridoid glycosides, two phenolic acids, and two flavonoid glycosides. The structural determination of the isolated compounds was performed by mono- and bidimensional NMR spectroscopic data, as well as ESI-MS experiments. All compounds were isolated from this species for the first time. The anti-angiogenic effects of the isolated iridoids were also reported on new blood vessels formation using the chick embryo chorioallantoic membrane as in vivo model. Results showed that among the isolated iridoids tested at the dose of 2 µg/egg, asperuloside (1), geniposidic acid (2), and iridoid V1 (3) reduced microvessel formation of the chorioallantoic membrane on morphological observations using a stereomicroscope. The anti-angiogenic effects of the active compounds, expressed as percentages of inhibition versus control, were 67% (1), 59% (2), and 54% (3), respectively. In addition, the active compounds were able to inhibit angiogenesis in the chorioallantoic membrane assay, in a dose-dependent manner (0.5-2 µg/egg) as compared to the standard retinoic acid.

RESUMO

ABSTRACT One new glucosidic iridoid, 6-O-veratroylbarlerin, was isolated from the chloroform/methanol extract of Isodon rubescens (Hemsl.) H.Hara, Lamiaceae aerial parts, along with the known compounds apigenin and caffeic acid. The structure of the new compound was elucidated on the basis of 1D and 2D NMR experiments and ESI-MS technique.

RESUMO

This study aimed to investigate the potential effect of plumieride, an iridoid glycoside isolated from Alamanda cathartica L. flowers, against dextran sulfate sodium (DSS)-induced colitis in mice. Colitis was induced in female swiss mice by adding DSS 3% to the drinking water. The animals were treated with vehicle (water), 5-aminosalicylic acid (100?mg/kg) or plumieride (10, 30 and 100?mg/kg) once a day, during 7 days. The body weight progression and the disease activity index was evaluated daily. On the eighth day, colons were collected for the measurement of the size, histological, histochemical, biochemical and inflammatory analysis. The cytotoxicity of plumieride on intestinal epithelial cell (IEC-6 cell line) was also evaluated. Plumieride, at dose of 100?mg/kg, significantly attenuated the mice weight loss, showed lower score in the disease activity index, diminished the colon shortening, improved the histological damage and avoided mucosa intestinal mucus depletion when compared with vehicle-treated only group. Moreover, plumieride was able to reduce the amount of colonic lipid hydroperoxides, while augmented reduced glutathione levels and superoxide dismutase activity. Although DSS intake stimulated an increase in myeloperoxidase activity and in tumor necrosis factor content on the colon tissue of the vehicle-treated group, the colons obtained from mice treated with plumieride did not present any of these changes. Taking together, the results of the present study disclose that plumieride exhibited a significant efficacy in attenuating the parameters of experimental ulcerative colitis, which may be mediated by an antioxidant and anti-inflammatory effect.

Assuntos

Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Colite/tratamento farmacológico , Furanos/farmacologia , Compostos de Espiro/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Apocynaceae/química , Linhagem Celular , Colite/patologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Furanos/administração & dosagem , Furanos/isolamento & purificação , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mesalamina/farmacologia , Camundongos , Ratos , Compostos de Espiro/administração & dosagem , Compostos de Espiro/isolamento & purificação , Fator de Necrose Tumoral alfa/metabolismo

RESUMO

The amount of damage that herbivorous insects impose on plants varies as a function of plant ontogenetic trajectories in tissue quality and defenses, and the herbivores' own developmental trajectories in body size, mandible shape and detoxification enzymes, among others. However, little is known about how host plant and herbivore ontogeny interact. Using four ontogenetic stages of Plantago lanceolata (Plantaginaceae) and three to five larval stages of the specialist caterpillar Junonia coenia (Nymphalidae), we evaluated how ontogenies in both of these trophic levels shape: (i) caterpillar feeding choice, (ii) performance, and (iii) sequestration of plant allelochemicals. Plant physical (leaf toughness) and chemical (iridoid glycosides) defenses increased, while nutritional quality (water and nitrogen content) decreased, as plants aged. These plant ontogenetic trajectories strongly altered the behavior and physiology of this specialist herbivore, but the magnitude of the response varied with larval stage. In feeding experiments, while first instar larvae showed little preference among plant stages, older larvae significantly preferred juvenile over reproductive stages. In turn, larval consumption increased and digestive efficiency decreased, potentially explaining their decrease in relative growth rate, as larvae and host plant aged, but differences were greater for younger than older caterpillars. Finally, sequestration of plant allelochemicals increased through plant and larval development; however, the major differences due to diet occurred earlier during larval development. Our results highlight that changes in plant ontogeny most strongly influence early herbivore instars, emphasizing the need to consider the developmental stage of both trophic levels to better understand temporal variation in herbivore damage.

Assuntos

Borboletas , Plantago , Animais , Herbivoria , Glicosídeos Iridoides , Larva

RESUMO

ABSTRACT Gentiana veitchiorum Hemsl., Gentianaceae, a traditional Tibetan medicine, was used for the treatment of liver jaundice with damp-heat pathogen, as well as for headache and chronic pharyngitis. A rapid ultra-performance liquid chromatography, photodiode array detector, quadrupole time-of-flight mass spectrometry method was developed for the fast and accurate identification and quantification of the chemical constituents of G. veitchiorum. In fact, eighteen compounds were detected and identified on the basis of their mass spectra, fragment characteristics and comparison with published data. Especially, the MS fragmentation pathways of iridoid glycosides and flavone C-glycosides were illustrated. Five compounds among them were quantified by UHPLC-PDA, including swertiamarin, gentiopicroside, sweroside, isoorientin, and isovitexin. The proposed method was then validated based on the analyses of linearity, accuracy, precision, and recovery. The overall recoveries for the five analytes ranged from 96.54% to 100.81%, with RSD from 1.05% to 1.82%. In addition, ten batches of G. veitchiorum from different areas were also analyzed. The developed method was rapid and reliable for both identification and quantification of the chemical constituents of G. veitchiorum, especially for simultaneous qualitative and quantitative analysis of iridoid glycosides and flavone C-glycosides.

RESUMO

Abstract A new iridoid glycoside, barlupulin C methyl ester (1), together with two known phenylethanoid glycosides (2 and 3) and three known simple phenolic glycosides (4-6) were isolated from the aerial parts of Barleria lupulina Lindl., Acanthaceae. The structure of the new compound (1) was elucidated through 1D and 2D NMR spectroscopic data, and HR-ESIMS. Interestingly, compound (1) has a formate group attached to the C-6 hydroxy group of the glucose unit. Compounds 2-6 were identified as poliumoside (2), decaffeoylacteoside (3), protocatechuic acid 4-O-β-glucoside (4), vanillic acid 4-O-β-glucoside (5), and leonuriside A (6) on the basis of NMR spectroscopic data analyses and comparison with those reported in the literature. Compounds 3-6 were isolated from B. lupulina for the first time.

RESUMO

A new iridoid glucoside has been isolated from the Chilean native Alonsoa meridionalis (L.f.) Kuntze. Its structure has been assigned as 6'-O-ß-d-glucopyranosyl-8-O-acetylharpagide (1) by using spectroscopic methods. Harpagoside (2), laterioside (3) and verbascoside (4) were also identified.

Assuntos

Glicosídeos Iridoides/isolamento & purificação , Scrophulariaceae/química , Chile , Glicosídeos , Glicosídeos Iridoides/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Piranos

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Castilleja tenuiflora Benth. (Orobanchaceae) is a perennial shrub used since the 16(th) century in Mexican traditional medicine for the treatment of a number of health disorders including inflammation, stomach pain and tumors. The aim of the present study was to evaluate the cytotoxic, anti-inflammatory and anti-ulcerogenic activities of ethyl acetate (EaE), methanol (ME) and aqueous extracts (AE) of Castilleja tenuiflora wild grown (CtW) and in vitro plants (CtIv). MATERIAL AND METHOD: Phytochemical analysis of the phenylethanoid glycoside (PhG) and iridoid glycoside (IG) components was carried out by chromatographic methods. In vitro cytotoxic activity of the extracts was evaluated in the following four carcinoma cell lines: colon (HF-6), breast (MCF-7), prostate (PC-3), and nasopharyngeal (KB). The topical anti-inflammatory activity was evaluated in mouse ear edema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Anti-ulcerogenic activity was evaluated in rats using an absolute ethanol-induced acute gastric ulcer model. RESULTS: The main compounds in the extracts were isoverbascoside, verbascoside and aucubin and their concentration depended both on the solvent used and on the plant material origin. None of the extracts showed cytotoxicity against the tested cell lines. In contrast, CtWEaE, CtWAE and CtIvEaE (1.6 mg/ear) showed moderate anti-inflammatory activity similar to dexamethasone (1 mg/ear) with a 38.2, 39.3 and 49.1% decrease of inflammation, respectively. CtWEaE and CtIvEaE (100 mg/kg) showed high anti-ulcerogenic activity with 88.3 and 83.1% inhibition, respectively, compared to famotidine (20 mg/kg, 32.8% inhibition). CONCLUSION: Castilleja tenuiflora extracts provided significant gastric protection in an acute ulcer induction model and topical anti-inflammatory activity in a mouse ear edema model. These activities are related to verbascoside and may explain the traditional use of Castilleja tenuiflora in the treatment of anti-inflammatory and gastrointestinal disorders. Cultured Castilleja tenuiflora plants (in vitro) exhibited pharmacological activities and also have the potential to produce bioactive compounds.

Assuntos

Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Orobanchaceae , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Etanol , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fitoterapia , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia

RESUMO

The methanol extract of the aerial parts of the medicinal plant Pedicularis sibthorpii Boiss., Scrophulariaceae, growing in the Azerbaijan province of Iran, was found to be active in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and the antibacterial agar well diffusion assays, but no general toxicity was observed in the brine shrimp lethality assay. A combination of solid-phase extraction (SPE) and preparative reversed-phase high-performance liquid chromatography (prep-RP-HPLC) analyses of the methanolic extract afforded three phenylethanoids (verbascoside, martynoside and isomartynoside), an iridoid (aucubin), a flavonoid (luteolin 7-O-β-D-glucopyranoside) and mannitol, and the structures of these compounds were elucidated unambiguously by spectroscopic means. The distribution of the isolated compounds within the genus Pedicularis has also been discussed.

RESUMO

Species of the genus Lantana, belonging to the family Verbenaceae, is among the various species studied scientifically. These species are mainly native to the tropical and subtropical regions of the Americas. Currently, they are present in various countries, where they are often grown as ornamental plants. For decades, species of Lantana have been of great interest for phytochemical, biological and pharmacological studies, which have been recently intensified. The components isolated from different species of Lantana cited in the literature constitute the focus of this review. Information ethnopharmacology of Lantana, as well as the activities of their different phytochemicals are discussed. In this review, it was observed that the genus Lantana has been widely studied in relation to its phytochemical components and terpenoids, flavonoids and phenylpropanoids are the more common secondary metabolites in Lantana. All these aspects, considered in this review, allow an evaluation of the ethnopharmacological potential of Lantana for the utilization of the large biomass of these plants.