RESUMO
Urtica circularis is an Argentinean species traditionally used to treat inflammation symptoms and oxidative stress-related diseases. Considering the uses in folk medicine, the purpose of this work was to evaluate and compare the anti-inflammatory and antioxidant activities of two different U. circularisextracts. The contribution of vicenin-2 and vitexin, two compounds identified in the phytochemical analysis, in the biological activity of the extracts was evaluated. The anti-inflammatory activity of the extracts and the isolated compounds was tested on lipopolysaccharide (LPS)-stimulated macrophages, while the antioxidant activity was evaluated through the 2,2 Ì diphenyl-1-picrylhydrazyl (DPPH) radical and 2,2 Ì-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) scavenging activities. The popular uses of both extracts were validated, i.e., the use of U. circularis ethanol extract for the treatment of inflammation, and the use of the aqueous extract to treat oxidative stress related-diseases. The differences in the biological activities observed between the extracts are probably due to qualitative and/or quantitative differences in the chemical composition and/or the occurrence of synergism between compounds.
Urtica circularis es una especie argentina utilizada para tratar los síntomas de la inflamación y enfermedades relacionadas con el estrés oxidativo. El objetivo de este trabajo fue evaluar y comparar las actividades anti-inflamatoria y antioxidante de dos extractos teniendo en cuenta su uso popular. Además, se analizó la participación de vicenina-2 y vitexina, compuestos identificados en el análisis fitoquímico, en la actividad de los extractos. La actividad anti-inflamatoria fue evaluada en macrófagos activados con lipopolisacárido (LPS). Se midió su actividad antioxidante con los métodos del 1,1,difenil-2-picril-hidrazilo (DPPH) y del ácido2,2 Ìazinobis-3 etilbenzotialzolin-6-sulfónico (ABTS). Los usos populares de ambos extractos fueron validados: el extracto etanólico para la inflamación y el extracto acuoso para el tratamiento de enfermedades relacionadas con el estrés oxidativo. Las diferencias en las actividades biológicas observadas entre los extractos están probablemente relacionadas con diferencias cualitativas y/o cuantitativas en su composición química y/o a la presencia de sinergismo entre compuestos
Assuntos
Urticaceae/química , Apigenina , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologiaRESUMO
While the fruits of Xylopia aethiopica (Dunal) A. Rich. are important in African countries as a local trade product, their composition remains scarcely investigated. Phenolic fingerprint is herein delivered through HPLC-DAD-ESI(Ion Trap)-MSn and UPLC-ESI-QTOF-MS2 analysis, six cinnamoylquinic acid derivatives and twenty-four flavonoid glycosides being determined, chrysoeriol-7-O-glycosides being the main constituents. A cytotoxicity screening of twenty-eight hydroethanol extracts, obtained from a collection of Guinea-Bissauan plants, against A549 and AGS carcinoma cells, revealed the selective and potent effect towards AGS cells (IC50 = 151 × 10-3 g L-1), upon exposure to the extract from X. aethiopica fruits. Additional experiments demonstrated insignificant effect on LDH release at 151 × 10-3 g L-1, morphological analysis further suggesting induction of apoptosis. Pro-apoptotic effects were confirmed, as the extract enabled the activation of the effector caspase-3, broadening the knowledge on the anticancer mechanisms elicited by the fruits of X. aethiopica. Phenolic constituents might contribute to the cytotoxic effects, particularly via caspase-3 activation. Considering that X. aethiopica fruit is very often referred as an anticancer ingredient in Africa, but mainly the potent cytotoxicity herein recorded, our results call for additional research aiming to identify non-phenolic constituents contributing to the effects and also to further detail the anticancer mechanisms.
Assuntos
Adenocarcinoma , Xylopia , África , Caspase 3 , Cromatografia Líquida de Alta Pressão , Frutas , Extratos Vegetais/farmacologia , Neoplasias GástricasRESUMO
The aim of this study was to investigate the effects of two structurally related flavonoids found in Cyclopia subternata, vicenin-2 (VCN) and scolymoside (SCL) on lipopolysaccharide (LPS)-induced liver failure in mice and to elucidate underlying mechanisms. Mice were treated intravenously with VCN or SCL at 12 h after LPS treatment. LPS significantly increased mortality, serum levels of alanine transaminase, aspartate transaminase, and inflammatory cytokines, and toll-like receptor 4 (TLR4) protein expression; these effects of LPS were inhibited by VCN or SCL. It also attenuated the LPS-induced activation of myeloid differentiation primary response gene 88 and TLR-associated activator of interferon-dependent signaling pathways of the TLR system. Our results suggest that VCN or SCL protects against LPS-induced liver damage by inhibiting the TLR-mediated inflammatory pathway, indicating its potential to treat liver diseases.
Assuntos
Apigenina/química , Glucosídeos/química , Inflamação/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Luteolina/química , Animais , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Transdução de SinaisRESUMO
The economic value of fig trees has been globally acknowledged due to their utilization in the food industry, being also frequently used in traditional medicine. While ubiquitously distributed in Southeast Asia, Ficus curtipes Corner remains uninvestigated concerning its biological properties and chemical profile. HPLC-DAD-ESI/MSn characterization of methanol extracts obtained from the stem bark and leaves allowed the identification and quantitation of 21 phenolic compounds for the first time; the stem bark was predominantly rich in flavan-3-ols and apigenin derivatives, while solely apigenin-di-glycosides have been identified and quantitated on the leaf extract. Both extracts inhibited 5-lipoxygenase (5-LOX) activity in a concentration-dependent manner, the one obtained from the stem bark being significantly more active (IC50 = 10.75 µg/mL). The effect of both extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages was evaluated, and while the stem bark extract did not lead to a noticeable interference on nitric oxide (NO) levels, the extract obtained from the leaves notably decreased NO and L-citrulline levels at concentrations ranging from 250 to 500 µg/mL. Herein, F. curtipes is valorized due to its modulatory effects on inflammatory mediators and also as a source of bioactive phenols, which may fuel further studies on the development of nutraceuticals.
Assuntos
Ficus/química , Lipopolissacarídeos/farmacologia , Inibidores de Lipoxigenase/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fenóis/farmacologia , Casca de Planta/química , Animais , Araquidonato 5-Lipoxigenase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores de Lipoxigenase/isolamento & purificação , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Fenóis/isolamento & purificação , Células RAW 264.7RESUMO
Ultrafiltration of Cyclopia genistoides extract was optimised to increase its benzophenone and xanthone content as quantified using HPLC-DAD. Regenerated cellulose (RC) and polyethersulphone membranes with molecular weight cut-offs of 10 and 30â¯kDa were evaluated in terms of compound enrichment, permeate flux and permeate yield, using dead-end ultrafiltration. Compound enrichment was subsequently optimised using the 10â¯kDa RC membrane and tangential flow ultrafiltration (TFU). The effect of extract composition on compound enrichment, due to natural variation in the source material, was assessed using extracts from different batches of plant material (nâ¯=â¯11). Transmembrane pressure and feed flow rate affected (pâ¯<â¯0.05) process efficiency (mean permeate flux, compound enrichment and membrane fouling). TFU achieved ≥20% enrichment of the target compounds, proving its suitability for preparation of a nutraceutical extract of C. genistoides.
Assuntos
Benzofenonas/análise , Fabaceae/metabolismo , Extratos Vegetais/química , Ultrafiltração/métodos , Xantonas/análise , Benzofenonas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Membranas Artificiais , Xantonas/isolamento & purificaçãoRESUMO
BACKGROUND: Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. The risk of developing diabetic foot ulcers for diabetic patients is 15% over their lifetime and approximately 85% of limb amputations is caused by non-healing ulcers. Unhealed, gangrenous wounds destroy the structural integrity of the skin, which acts as a protective barrier that prevents the invasion of external noxious agents into the body. Vicenin-2 (VCN-2) has been reported to contain prospective anti-oxidant and anti-inflammatory properties that enhance cell proliferation and migration. Sodium Alginate (SA) is a natural polysaccharide that possesses gel forming properties and has biodegradable and biocompatible characteristics. Therefore, the objective of this study is to evaluate the effect of SA wound dressings containing VCN-2 on diabetic wounds. METHODS: Wounds were inflicted in type-1 diabetic-streptozotocin (STZ) induced male Sprague Dawley rats. Subsequently, relevant groups were topically treated with the indicated concentrations (12.5, 25 and 50 µM) of VCN-2 hydrocolloid film over the study duration (14 days). The control group was treated with vehicle dressing (blank or allantoin). Wounded tissues and blood serum were collected on 0, 7 and 14 days prior to sacrifice. Appropriate wound assessments such as histological tests, nitric oxide assays, enzyme-linked immunosorbent assays (ELISA) and immunoblotting assays were conducted to confirm wound healing efficacy in the in vivo model. One-way Analysis of Variance (ANOVA) was used for statistical analysis. RESULTS: Results showed that hydrocolloid film was recapitulated with VCN-2 enhanced diabetic wound healing in a dose-dependent manner. VCN-2 reduced pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α), mediators (iNOS and COX-2), and nitric oxide (NO) via the NF-κB pathway. Data suggests that the VCN-2 film facilitated healing in hyperglycemic conditions by releasing growth factors such as (VEGF and TGF-ß) to enhance cell proliferation, migration, and wound contraction via the VEGF and TGF-ß mechanism pathways. CONCLUSIONS: This study's findings suggest that VCN-2 may possess wound healing potential since topical treatment with VCN-2 hydrocolloid films effectively enhanced wound healing in hyperglycemic conditions.
Assuntos
Alginatos , Apigenina , Curativos Hidrocoloides , Pé Diabético/tratamento farmacológico , Glucosídeos , Cicatrização/efeitos dos fármacos , Alginatos/administração & dosagem , Alginatos/uso terapêutico , Animais , Apigenina/administração & dosagem , Apigenina/farmacologia , Apigenina/uso terapêutico , Modelos Animais de Doenças , Glucosídeos/administração & dosagem , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Exposure of ultraviolet (UV) radiation is the major factor from environment to cause erethema, inflammation, photoaging and skin carcinogenesis. Vicenin-2, a bioflavonoid which are isolated from several medicinal plants. The present study was demonstrated the role of vicenin-2 on UVB linked oxidative stress and photoaging signaling in human dermal fibroblasts (HDF). In this study, UVB-irradiation (100â¯mJ/cm2) significantly elevated the intracellular ROS levels, lipid peroxidation, DNA damage, depletion of antioxidants resulted in apoptotic HDF cells. Interestingly, HDF cells were administrated with vicenin-2, 1â¯h before UVB-irradiation prevents ROS generation, TBARS, apoptotic changes and DNA damage in HDF. MAPKs and MMP signaling are implicated in oxidative stress and photoaging; these signaling events are considered as photoaging and differentiation. We found that Vicenin-2 prevents over expression of MAPKs (p-ERK1, p-JNK & p-p38), AP-1 and MMPs (MMP-2, 9 & 12) in during the exposure of UVB in HDF cells. These findings conclude that vicenin-2 could be a potential bioactive ingredient to absorb UV photons and protects the dermal cells from the UVB associated oxidative stress and photoaging signaling due to sunscreen properties.
Assuntos
Apigenina/uso terapêutico , Fibroblastos/efeitos da radiação , Glucosídeos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Apigenina/farmacologia , Linhagem Celular , Glucosídeos/farmacologia , Humanos , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Substâncias Protetoras/farmacologia , Transdução de Sinais , Pele/patologiaRESUMO
The bitter taste of Cyclopia genistoides infusions is unacceptable to consumers, who are used to the slightly sweet taste of the herbal teas produced from other Cyclopia species. Bitter taste intensities of crude phenolic fractions of a bitter hot water extract of C. genistoides were determined by a trained panel to identify the fraction contributing most to the bitter taste. Fractions, enriched in benzophenones (B), xanthones (X) and flavanones (F), and each tested at their infusion equivalent concentration (IEC) scored 5, 31 and 13 (on a 100-point scale), respectively. Fraction B, containing mostly iriflophenone glucosides, was perceived as not bitter. The major xanthone in fraction X, mangiferin, was significantly (pâ¯<â¯0.05) more bitter than its regio-isomer, isomangiferin, at equal concentration. A mixture of isomangiferin and mangiferin at their IECs was significantly (pâ¯<â¯0.05) less bitter than the mangiferin solution alone, indicating bitter suppression by isomangiferin.
Assuntos
Fabaceae/química , Fenóis/análise , Paladar , Chás de Ervas/análise , Fenóis/química , EstereoisomerismoRESUMO
BACKGROUND: Colorectal cancer (CRC) is among highest prevailing cancers in the whole world, especially in western countries. For a diverse of reasons, patients prefer naturally occurring dietary substances over synthetic agents to prevent cancer. Vicenin-2 is largely available in a medicinal plant Ocimum sanctum and is an apigenin form, 6,8-di-C-glucoside, which has been reported to have a range of pharmacological values which includes antioxidant, hepatoprotective, anti-inflammatory and anti-cancer. This study was aimed to analyze the anti-proliferative effect of Vicenin-2 on human colon cancer cells via the Wnt/ß-catenin signaling inhibition. METHODS: MTT assay was used to assess the cell viability at different concentrations and time point. Vicenin-2 at a concentration of 50 µM (IC50) decreased the phosphorylated (inactive) glycogen synthase kinase-3ß, cyclin D1, and non-p-ß-catenin expressions in HT-29 cells, which were evidenced through western blot analysis. RESULTS: Further, Vincenin-2 reduced the T-cell factor (TCF) / Leukocyte erythroid factor (LEF) reporter activity in HT-29 cells. Vicenin-2 also promoted substantial cell cycle arrest at the G2M phase of HT-29 cells, as well induced apoptosis in HT-29 cells, as revealed through flow cytometric analysis. Furthermore, immunoblot analysis showed that Vicenin-2 treatment enhanced the expression of Cytochrome C, Bax and caspase-3 whereas suppressed the Bcl-2 expression. CONCLUSION: Together, these results revealed that Vicenin-2 can act as a potent inhibitor of HT-29 cell proliferation and can be used as an agent against CRC.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Glucosídeos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Relação Dose-Resposta a Droga , Células HT29 , Humanos , Relação Estrutura-Atividade , Células Tumorais Cultivadas , beta Catenina/metabolismoRESUMO
The small tree Allophylus africanus, widespread in the African continent, has long been considered valuable, as noted by the number of reports on their multiple medicinal uses. With this work, we aimed to extend the current, and so far restricted, knowledge on the chemical composition of the plant, particularly as source of flavonoids, as well as to assess its potential anti-inflammatory properties. The chemical characterization of the aqueous extract obtained from the leaves allowed the identification and quantitation of 30 flavones, predominantly apigenin derivatives, but also four luteolin derivatives, while the stem bark extract was solely characterized by apigenin di-C-glycosides and mono-C-glycosides-O-glycosylated. Strong inhibitory effects towards 5-lipoxygenase were observed with the aqueous extracts obtained from the leaves and stem bark, with IC50 values of 41.28 and 107.77⯵gâ¯mL-1, respectively. Both extracts were also found to reduce NO levels in LPS-challenged RAW 264.7 macrophages, without noticeable cytotoxicity. The flavonoid profile of the plant is disclosed for the first time, allowing the identification of several molecules that may contribute to mitigate the inflammatory response. Jointly, with the current study the anti-inflammatory use of the leaves and stem bark is partially validated.
Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Paullinia/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Anti-Inflamatórios/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Flavonoides/isolamento & purificação , Limite de Detecção , Inibidores de Lipoxigenase/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Células RAW 264.7 , Reprodutibilidade dos Testes , Espectrofotometria UltravioletaRESUMO
Cymbidium kanran, an orchid exclusively distributed in Northeast Asia, has been highly valued as a decorative plant and traditional herbal medicine. Here, C. kanran extracts were prepared in 70% aqueous methanol using ultrasound-assisted extraction (UAE) and subjected to liquid chromatography-photodiode array detection and ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry analysis, which were used for quantitative and qualitative analysis, respectively. It was found that the extracts were rich in flavone C-glycosides including vicenin-2, vicenin-3, schaftoside, vitexin, and isovitexin. Ten deep eutectic solvents (DESs) were synthesized by combining choline chloride (hydrogen bond acceptor) with various polyols and diols (hydrogen bond donors) and were tested as a medium for the efficient production of extracts enriched with potentially bioactive flavone C-glycosides from C. kanran. A DES named ChCl:DPG, composed of choline chloride and dipropylene glycol at a 1:4 molar ratio, exhibited the best extraction yields. Then, the effects of extraction conditions on the extraction efficiency were investigated by response surface methodology. Lower water content in the extraction solvent and longer extraction time during UAE were desirable for higher extraction yields. Under the statistically optimized conditions, in which 100 mg of C. kanran powder were extracted in 0.53 mL of a mixture of ChCl:DPG and water (74:26, w/w) for 86 min, a total of 3.441 mg g-1 flavone C-glycosides including 1.933 mg g-1 vicenin-2 was obtained. This total yield was 196%, 131%, and 71% more than those obtained using 100% methanol, water, and 70% methanol, respectively.
Assuntos
Flavonas/química , Monossacarídeos/química , Orchidaceae/química , Extratos Vegetais/química , Solventes/química , Apigenina/química , Glucosídeos/química , GlicosídeosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia campestris L. (Asteraceae) has many traditional uses, among which treatment of diabetes and hypertension. AIM OF THE STUDY: This study was conducted in order to confirm the antihypertensive and hypotensive effects of A. campestris L. aqueous extract (AcAE) and to explore the underlying mechanism of action of its vasorelaxant effect, besides the acute toxicity. Also, the chemical composition of AcAE was investigated. MATERIAL AND METHODS: the chemical content of AcAE was determined by using HPLC and NMR techniques. The antihypertensive effect was assessed indirectly by tail-cuff method on L-NAME induced hypertensive rats, while the hypotensive action was monitored intravenously by invasive method on normotensive rats. The vasorelaxant effect and vascular mechanism of action were studied in the presence of antagonists and blockers on aorta isolated from normotensive rats. On the other side, the acute toxicity was studied by oral feeding of extract to the mice. RESULTS: The global phytochemical profile of AcAE reveals the presence of several polyphenols as main components. A. campestris L. infusion was characterized by mono- and di-cinnamoyl compounds, with 3,5-dicaffeoylquinic (isochlorogenic A) acid being the main compound, followed by 5-caffeoylquinic (chlorogenic) acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant compound among flavonoids. The daily treatment with AcAE at 150mg/kg/day prevented the installation of hypertension on L-NAME hypertensive rats, and reduced SBP from 172mmHg up to 144mmHg. At the dose 40mg/kg, AcAE provoked reduction of systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP), without affecting the heart rate. Also, AcAE (10-2-2mg/ml) relaxed the precontracted aorta by 95.8±1.3%. The denudation and preincubation of aorta with atropine, calmidazolium, L-NAME, hydroxycobalamin, ODQ, 8-RP-Br-PET-cGMP, thapsigargin and verapamil attenuated the vasorelaxant response, while the pre-treatment with 4-AP, TEA, glibenclamide and BaCl2 did not alter this effect. The oral administration of AcAE (0-6g/kg) reveals no mortality or toxicity. CONCLUSIONS: our study proved that AcAE possess an important antihypertensive, hypotensive and vasorelaxant effect, which is mediated via calmodulin-NO-cGC-PKG pathway, and via inhibition of calcium influx through voltage-operated calcium channels and activation of intracellular calcium mobilization into sarcoplasmic reticulum. Therefore, our findings give first evidence about the traditional use of A. campestris L. as antihypertensive plant.
Assuntos
Anti-Hipertensivos/farmacologia , Artemisia/química , Extratos Vegetais/farmacologia , Vasodilatadores/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Camundongos , Marrocos , Ratos , Ratos Wistar , Espectrofotometria UltravioletaRESUMO
Diabetic foot ulcer is a serious complication of diabetes, which affects a significant percentage (15%) of diabetics and up to 15%-24% of those affected may require amputation. Therefore, the economic burden of diabetic foot ulcers is enormous and is associated with high cost of treatment and prolongs hospitalization. The present study was conducted to evaluate antibacterial and in vivo wound healing activities of an aqueous fraction of Moringa oleifera on a diabetic condition. Antibacterial activity testing was carried out using agar well and tube dilution techniques. The in vivo study was conducted using six groups of animals that comprise of one normal and diabetic control group each, three treatment groups of 0.5%, 1%, and 2% w/w aqueous fraction, and a positive control group (1% w/w silver sulfadiazine). Rats were induced with diabetes using a combination of streptozotocin 65 and 150 mg/kg nicotinamide daily for 2 days, and excision wounds were created and treated with various doses (0.5%, 1%, and 2% w/w aqueous fraction) daily for 21 days. Biophysical, histological, and biochemical parameters were investigated. The results of the study revealed that aqueous fraction possessed antibacterial activity through inhibition of growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli organisms. The topical application of aqueous fraction revealed enhancement of wound healing under sustained hyperglycemic condition for the duration of the experiment. This enhancement was achieved through decreased wound size, improved wound contraction, and tissue regeneration, as well as downregulation of inflammatory mediators, such as tumor necrosis factor-α, interleukin-1ß, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2, and upregulation of an angiogenic marker vascular endothelial growth factor in wound tissue treated with various doses of aqueous fraction of M. oleifera. The findings suggest that aqueous fraction of M. oleifera containing Vicenin-2 active compound may accelerate wound healing in hyperglycemic condition.
Assuntos
Antibacterianos/farmacologia , Apigenina/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Glucosídeos/farmacologia , Moringa oleifera/química , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Apigenina/química , Apigenina/isolamento & purificação , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Experimental/fisiopatologia , Pé Diabético/microbiologia , Pé Diabético/patologia , Pé Diabético/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Glucosídeos/química , Glucosídeos/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana , Niacinamida/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Estreptozocina/administração & dosagem , Relação Estrutura-Atividade , Água/químicaRESUMO
AIM AND OBJECTIVE: Recent results indicate that polyphosphate (polyP) released by human endothelial cells can function as a pro-inflammatory mediator. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. This study was undertaken to investigate whether two structurally related active compounds found in C. subternata, namely vicenin-2 and scolymoside, can modulate polyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. METHODS: The anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in polyP-activated HUVECs and mice. In addition, the beneficial effects of vicenin-2 and scolymoside on survival rate in polyP-injected mice were determined. RESULTS: We found that vicenin-2 and scolymoside inhibits polyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, polyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by vicenin-2 and scolymoside in HUVECs. These anti-inflammatory functions of vicenin-2 and scolymoside were confirmed in polyP-injected mice. CONCLUSIONS: These results suggest that vicenin-2 and scolymoside have therapeutic potential for various systemic inflammatory diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Glucosídeos/farmacologia , Luteolina/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Apigenina/uso terapêutico , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Endotoxemia/tratamento farmacológico , Endotoxemia/metabolismo , Glucosídeos/uso terapêutico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Luteolina/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , PolifosfatosRESUMO
Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, which are 2 active compounds from C. subternata that act against high mobility group box 1 (HMGB1)-mediated septic responses in human umbilical vein endothelial cells (HUVECs) and mice. The antiseptic activities of vicenin-2 and scolymoside were determined by measuring permeability, neutrophil adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. According to the results, vicenin-2 and scolymoside effectively inhibited lipopolysaccharide-induced release of HMGB1, and suppressed HMGB1-mediated septic responses such as hyperpermeability, the adhesion and migration of leukocytes, and the expression of cell adhesion molecules. In addition, vicenin-2 and scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6, and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
Assuntos
Anti-Infecciosos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Cyclopia (Planta) , Glucosídeos/farmacologia , Proteína HMGB1/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Luteolina/farmacologia , Sepse/tratamento farmacológico , Animais , Apigenina/isolamento & purificação , Adesão Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Cyclopia (Planta)/química , Glucosídeos/isolamento & purificação , Proteína HMGB1/antagonistas & inibidores , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Luteolina/isolamento & purificação , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fitoterapia , Plantas Medicinais , Sepse/metabolismo , Sepse/microbiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Transforming growth factor ß-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-ß. TGFBIp is released by the human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, two active compounds in C. subternata against TGFBIp-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of vicenin-2 or scolymoside were determined by measuring permeability, human neutrophils adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated HUVECs and mice. According to the results, vicenin-2 or scolymoside effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, vicenin-2 or scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6 and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by TGFBIp. Vicenin-2 or scolymoside reduced cecal ligation and puncture (CLP)-induced septic mortality and pulmonary injury. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.
Assuntos
Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Cyclopia (Planta) , Proteínas da Matriz Extracelular/metabolismo , Glucosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Luteolina/farmacologia , Extratos Vegetais/farmacologia , Sepse/prevenção & controle , Fator de Crescimento Transformador beta/metabolismo , Animais , Anti-Inflamatórios/isolamento & purificação , Apigenina/isolamento & purificação , Permeabilidade Capilar/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Quimiotaxia de Leucócito/efeitos dos fármacos , Cyclopia (Planta)/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ativação Enzimática , Proteínas da Matriz Extracelular/imunologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glucosídeos/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/imunologia , Mediadores da Inflamação/metabolismo , Luteolina/isolamento & purificação , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Edema Pulmonar/imunologia , Edema Pulmonar/prevenção & controle , Sepse/imunologia , Sepse/metabolismo , Sepse/microbiologia , Fatores de Tempo , Fator de Crescimento Transformador beta/imunologiaRESUMO
Vicenin 2, isolated from a traditionally used medicinal plant Artemisia capillaris, is a 6,8-di-C-glucoside of apigenin which has been previously reported to possess a wide variety of pharmacological activities including antioxidant, anti-inflammatory, anti-cancer, and hepatoprotective. However, there have not been any reports concerning its anti-diabetic potential until now. Therefore, in the present study, we evaluated the anti-diabetic potential of vicenin 2 via α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), rat lens aldose reductase (RLAR), and advanced glycation end products (AGE) formation inhibitory assays. Vicenin 2 strongly inhibited α-glucosidase, PTP1B, and RLAR in the corresponding assays. In addition, vicenin 2 inhibited the formation of both fluorescent AGE and nonfluorescent AGE, e.g., CML, as well as the level of fructosamine in glucose-fructose-induced bovine serum albumin (BSA) glycation. In the test system, vicenin 2 suppressed glycation-induced protein oxidation by attenuating the formation of protein carbonyl groups as well as by inhibiting the modification of protein thiol groups. Moreover, vicenin 2 was found to be a potent inhibitor of glycation-induced formation of amyloid cross-ß structures in BSA. Taken together, vicenin 2 might be a useful lead for the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-associated complications.
Assuntos
Apigenina/isolamento & purificação , Apigenina/farmacologia , Artemisia/química , Inibidores Enzimáticos/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Produtos Finais de Glicação Avançada/metabolismo , Aldeído Redutase/antagonistas & inibidores , Aldeído Redutase/metabolismo , Amiloide/química , Amiloide/efeitos dos fármacos , Animais , Apigenina/química , Frutosamina/metabolismo , Glucosídeos/química , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/farmacologia , Cristalino/enzimologia , Lisina/análogos & derivados , Lisina/metabolismo , Oxirredução , Plantas Medicinais/química , Carbonilação Proteica/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Ratos Sprague-Dawley , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , alfa-Glucosidases/metabolismoRESUMO
Siparuna guianensis Aubl., Siparunaceae, is used as anxiolytic plants in folk medicine by South-American indians, "caboclos" and river-dwellers. This work focused the evaluation of phenolic composition of hydroethanolic extract of S. guianensis through HPLC-DAD-ESI/MS/MS. The constituents exhibited protonated, deprotonated and sodiated molecules and the MS/MS fragmentation of protonated, deprotonated and sodiated molecules provided product ions with rich structural information. Vicenin-2 (apigenin-6,8-di-C-glucoside) was the main constituent found in S. guianensis together quercetin-3,7-di-O-rhamnoside and kaempferol-3,7di-O-rhamnoside. A commercial extract of Passiflora incarnata (Phytomedicine) was used as surrogate standard and also was analyzed through HPLC-DAD-ESI/ MS/MS, showing flavones C-glycosides as constituents, among them, vicenin-2 and vitexin. The main constituent was vitexin. Flavonols triglycosides was also found in low content in S. guianensis and were tentatively characterized as quercetin-3O-rutinoside-7-O-rhamnoside, quercetin-3-O-pentosyl-pentoside-7-O-rhamnoside and kaempferol-3-O-pentosyl-pentoside-7-O-rhamnoside. Apigenin and kaempferol derivatives had been reported as anxiolytic agents. Flavonoids present in this extract were correlated with flavonoids reported as anxiolytics.
RESUMO
Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) is a medicinal plant popularly used as an anti-ulcer medicine. The plant native from Southern Brazil was chemically investigated and tested for its in vivo gastric anti-ulcer property by chloride acid/ethanol model. The chromatographic analysis of the hydroethanol extract of its leaves revealed the presence of C-glycosylflavonoids. From the n-butanol fraction of the hydroethanol extract of its aerial parts, vicenin-2 was isolated as the main component and identified by spectroscopic methods; and, a direct comparison with authentic samples was made. This fraction afforded three other C-glycosylflavonoids: vitexin, orientin and swertisin; all of them identified by direct comparison with authentic samples. We found that the oral administration of aqueous and hydroethanolic extracts led to a significant decrease in the ulcer index.
Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) é uma espécie vegetal nativa do Sul do Brasil e usada externamente na medicina popular para o tratamento de úlcera na pele. Neste trabalho foi estudada a atividade antiúlcera gástrica em ratos usando como indutor ácido clorídrico/etanol. Os extratos hidroetanólico e aquoso apresentaram atividade antiúlcera no modelo utilizado. A análise cromatográfica do extrato hidroetanólico das folhas indicou a presença de C-glicosilflavonóides. Da fração n-butanólica obtida por extração seqüencial do extrato hidroetanólico foi isolada e identificada por métodos espectroscópicos a vicenina-2 como substância majoritária. Desta fração também foram identificados por CCD bidimensional, com auxílio de substâncias de referência, outros três C-glicosídeos: vitexina, orientina e swertisina.
RESUMO
AIM: To develop an RP-HPLC method for preparing the reference substanc of vicenin-2 in Desmodium styracifolium. METHODS: Ethanol-extract of desmodium styracifolium was isolated and purified by RP-HPLC combining solvent extraction with column chromatography and recrystalliztion.The purity and content of vicenin-2 were identified by HPLC. RESULTS: The flvonoids were completely separated under this chromatographic condition.The purity of the reference substance was 99.0% or above. CONCLUSION: The method is simple,accurate,better on repeatability,and effective to yield high-purity product.It can be used as reference substance for the research of herbal medicine.