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1.
J Ethnopharmacol ; 330: 118188, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-38608797

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The species Jatropha gossypiifolia, popularly known as "pinhão-roxo", is distributed throughout Brazil, is commonly employed for topical or oral administration in treating wounds, inflammations, and snake bites. Given the significant impact of snakebites on public health and the limitations of antivenom, coupled with the diverse molecular composition of this plant species, investigating its healing and antidermonecrotic capacities is relevant. AIM OF THE STUDY: This study aimed to develop a topical nanoemulsion incorporating the hydroethanolic extract of J. gossypiifolia leaves, to evaluate its therapeutic potential, particularly in terms of its efficacy in wound healing and inhibition of dermonecrosis induced by B. erythromelas venom (BeV). MATERIAL AND METHODS: The extract of J. gossypiifolia (JgE) leaves was obtained by maceration and remaceration. The phytochemical analysis was conducted and J. gossypiifolia nanoemulsion (JgNe) was obtained, characterized and assessed for stability. The cytotoxicity was determined in normal cells (erythrocytes and 3T3) using hemolytic assay and cell viability assay using crystal violet staining. The antioxidant activity was evaluated by the reduction of ABTS and DPPH radicals. The evaluation of wound healing was conducted in vivo following treatment with JgNe, wherein the percentage of wound closure and inflammatory mediators. The skin irritation test was assessed in vivo by applying JgNe directly to the animal's skin. In vitro, the antivenom capacity was evaluated through enzymatic inhibition assays (phospholipase A2 and hyaluronidase) of BeV. Additionally, the in vivo antidermonecrotic activity of JgNe was evaluated by measuring the reduction of the dermonecrotic halo. RESULTS: The HPLC-DAD analysis identified flavonoids, specifically vitexin, luteolin derivatives and apigenin derivatives. In addition, 95.08 ± 5.46 mg of gallic acid/g of extract and 137.92 ± 0.99 mg quercetin/g extract, was quantified. JgNe maintained stability over a 4-week period. Moreover, JgE and JgNe demonstrated no cytotoxicity in human erythrocytes and murine fibroblasts at tested concentrations (32.25-250 µg/mL). Additionally, exhibited significant antioxidant activity by reducing ABTS and DPPH radicals. The treatment with JgNe did not induce skin irritation and accelerated wound healing, with significant wound closure observed from 5th day and reduction in nitrite levels, myeloperoxidase activity, and cytokine. Both JgE and JgNe demonstrated in vitro inhibition of the phospholipase and hyaluronidase enzymes of BeV. Moreover, JgNe exhibited antidermonecrotic activity by reducing the dermonecrotic halo caused by BeV after 24 h. CONCLUSIONS: JgNe and JgE exhibited no cytotoxicity at the tested concentrations. Additionally, our findings demonstrate that JgNe has the ability to accelerate wound closure and reduce dermonecrosis caused by BeV, indicating to be promising formulation for complementary therapy to antivenom treatment.


Asunto(s)
Bothrops , Venenos de Crotálidos , Emulsiones , Necrosis , Extractos Vegetales , Hojas de la Planta , Cicatrización de Heridas , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Cicatrización de Heridas/efectos de los fármacos , Hojas de la Planta/química , Venenos de Crotálidos/toxicidad , Ratones , Masculino , Necrosis/tratamiento farmacológico , Piel/efectos de los fármacos , Piel/patología , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Células 3T3 , Hemólisis/efectos de los fármacos , Ratas Wistar , Nanopartículas/química , Serpientes Venenosas
2.
Biomed Pharmacother ; 149: 112921, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-36068780

RESUMEN

The growing use of phytotherapy in clinical practice arouses interest in studies using medicinal plants as active ingredients for new medicines. Ipomoea pes-caprae has a wide medicinal use in the treatment of inflammatory disorders, skin wounds, stings, and painful rheumatic processes. Assayed in this study are the physicochemical characterization of a gel developed with this extract and the evaluation of its anti-inflammatory and healing efficacy, in addition to its antiedematogenic action on Bothrops snake envenoming in mice. The qualitative and quantitative analyses of the hydroethanolic extract by mass spectrometry showed 18 phenolic compounds, highlighting a high content of chlorogenic acid (0.92 µg/g), neochlorogenic acid (6.07 µg/g), and isochlorogenic acid (0.80 µg/g) compounds. The formulation was stable in relation to the physical-chemical characteristics during the time of analysis and was considered safe for topical treatment in animals, causing no skin irritation. Although the results have shown an absence of activity in the model of ear edema induced by croton oil (acute inflammation), the herbal gel efficiently inhibited carrageenan paw edema and chronic ear edema induced by multiple applications of croton oil, which may indicate the possible performance under the kinin pathway such as bradykinin, histamine, and serotonin. Wound healing in the group treated with the I. pes-caprae gel was accelerated compared with the placebo group, also confirmed through histological data. Edema induced by Bothrops erythromelas snake venom was efficiently reduced in the treatment with I. pes-caprae gel associated with the antibothropic-crotalic serum, whereas the antivenom alone was not effective. This approach presents a promising formulation based on I. pes-caprae with potential therapeutic use for inflammatory disorders.


Asunto(s)
Bothrops , Convolvulaceae , Ipomoea , Mordeduras de Serpientes , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antivenenos/farmacología , Aceite de Crotón/farmacología , Edema/inducido químicamente , Geles/farmacología , Ratones , Fenoles/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Mordeduras de Serpientes/tratamiento farmacológico , Venenos de Serpiente/farmacología , Cicatrización de Heridas
3.
Front Pharmacol ; 13: 1104705, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36712663

RESUMEN

Bryophyllum pinnatum (Crassulaceae) is used in traditional medicine for treating skin wounds. In our previous study, a topical gel containing B. pinnatum aqueous leaf extract showed a preclinical anti-inflammatory effect in in vivo acute edema models. In continuation, the present study aims to evaluate the phytochemical content and the stability of a formulation in gel containing B. pinnatum aqueous leaf extract and its healing properties and mechanism of action through an experimental model of induction of skin wounds in rats and in vitro assays. The animals were treated topically for 7 or 14 days with a formulation in gel containing extract at 5% or a placebo or Fibrinase® in cream. In addition, to establish some quality control parameters, the total phenolic content (TPC), total flavonoid content (TFC), and a study focusing on the phytochemical and biological stability of a gel for 30 days at two different conditions (room temperature and 40°C/75% RH) were performed. Gel formulation containing extract showed a TPC and TFC of 2.77 ± 0.06 mg of gallic acid/g and 1.58 ± 0.03 mg of quercetin/g, respectively. Regarding the stability study, the formulation in gel showed no significant change in the following parameters: pH, water activity, chromatographic profile, and the content of the major compound identified in the extract. The gel formulation containing extract stimulated skin wound healing while reducing the wound area, as well as decreasing the inflammatory infiltrate, reducing the levels of IL-1ß and TNF-α, and stimulating angiogenesis with increased expression of VEGF, an effect similar to Fibrinase. In conclusion, the gel formulation containing extract exhibited relevant skin wound healing properties and, therefore, has the potential to be applied as a novel active ingredient for developing wound healing pharmaceuticals.

4.
Toxicon ; 179: 42-52, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32174508

RESUMEN

Scorpionism represents a serious public health problem due to its increasing incidence. In Brazil, Tityus serrulatus is a species of major medical importance, especially in children and the elderly, as envenomation may induce serious acute pulmonary edema. "Mangaba" (Hancornia speciosa Gomes) fruit juice is popularly used in the treatment of several inflammatory disorders. The objective of this study was to analyze the chemical composition of fruit juice of H. speciosa by HPLC-DAD-MS/MS, as well as to evaluate its anti-inflammatory potential and antioxidant activity, and analyze the biochemical and hematological parameters in acute pulmonary edema induced by T. serrulatus venom (TsV) in mice. Mice were challenged with TsV (30 µg/kg, subcutaneously) and were treated with dexamethasone (2 mg/kg, intraperitoneally) or fruit juice (pre- or post-treatment protocols, by intra-gastric route at 100 and 200 mg/kg), and 2 h later were anesthetized for blood, lung, and kidney collection, for several biochemical analyses. Results showed that the juice decreased edema, myeloperoxidase levels, vascular permeability, and production of cytokines (IL-1ß, IL-6, and TNF-α) in lung tissue. Also, the juice reduced the concentration of nitrite and malondialdehyde oxidative stress markers in renal tissue. Amylase, lactate dehydrogenase, aspartate aminotransferase, and creatine kinase seric levels were reduced when the animals were treated with the juice. HPLC-DAD-MS/MS analysis identified 13 phenolic derivatives. The results suggest that the juice was able to decrease the inflammatory effects induced by T. serrulatus, demonstrating that the use of juice can be relevant for the treatment of scorpion stings.


Asunto(s)
Antiinflamatorios/uso terapéutico , Apocynaceae/química , Extractos Vegetales/uso terapéutico , Edema Pulmonar/tratamiento farmacológico , Picaduras de Escorpión/tratamiento farmacológico , Venenos de Escorpión/toxicidad , Animales , Antiinflamatorios/farmacología , Humanos , Extractos Vegetales/farmacología , Edema Pulmonar/inducido químicamente , Escorpiones
5.
Biomed Pharmacother ; 113: 108721, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30856538

RESUMEN

Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine in the treatment of wound healing. In this context, the objective of the present study was to evaluate the local anti-inflammatory activity of a topical formulation containing aqueous extract of both species. The in vivo model used was ear edema induced by croton oil and paw edema induced by carrageenan. The Swiss mice treatments use formulations containing aqueous extract at different concentrations (1.25%, 2.5%, and 5%) or dexamethasone (1 mg/g), all administered topically and immediately after edema induction. The treatment with formulations containing aqueous extract of both species reduced ear and paw edema, besides that, the decrease in edema was evidenced by reduction of myeloperoxidase activity, IL-1ß, and TNF-α levels and increase IL-10 levels. In conclusion, the two species showed local anti-inflammatory activity; however K. brasiliensis showed a better result in both edematogenic models since it had activity in the lowest concentration.


Asunto(s)
Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Kalanchoe/química , Extractos Vegetales/farmacología , Administración Cutánea , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Carragenina/toxicidad , Aceite de Crotón/toxicidad , Dexametasona/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/tratamiento farmacológico , Edema/patología , Femenino , Inflamación/patología , Interleucina-1beta/metabolismo , Masculino , Ratones , Peroxidasa/metabolismo , Extractos Vegetales/administración & dosificación , Hojas de la Planta , Factor de Necrosis Tumoral alfa/metabolismo , Agua/química
6.
Toxicon ; 164: 1-9, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30902683

RESUMEN

Scorpion envenomation has been considered a public health issue around the world. Tityus serrulatus represents a specie of major medical importance in Brazil due to mortality rates of approximately 1% among children and elderly populations. The aim of this work was to evaluate the in vivo anti-inflammatory potential of aqueous extract from Hancornia speciosa fruits, its fractions and its phenolic compounds against T. serrulatus envenomation. After receiving the T. serrulatus venom (TsV, 0.8 mg/kg) intraperitoneally, the animals were treated intravenously with the aqueous extract (20, 30 and 40 mg/kg), the arachnid antivenom (50 µL/animal), the dichloromethane, ethyl acetate and n-butanol fractions (20 mg/kg) as well as rutin and chlorogenic acid (2, 2.5 and 5 mg/kg). The treatment with the aqueous extract, fractions and phenolic compounds decreased the migration of leukocytes to the peritoneal cavity and reduced the levels of IL-1ß, IL-6 and IL-12. Moreover, the pulmonary histopathologic analysis showed a reduction in both interstitial and alveolar edema, as well as in the leukocytes infiltration and vascular ectasia in the mice's lungs, which evidences a protective effect attributed to H. speciosa. This is the first study that demonstrates the inhibitory potential of the aqueous extract from H. speciosa fruits against inflammation induced by TsV. These findings suggest that the bioactive compounds from the aqueous extract, especially chlorogenic acid and rutin, are responsible for the reported anti-inflammatory activity of H. speciosa.


Asunto(s)
Antiinflamatorios/farmacología , Apocynaceae/química , Fenoles/farmacología , Extractos Vegetales/farmacología , Neumonía/tratamiento farmacológico , Venenos de Escorpión/toxicidad , Animales , Antiinflamatorios/uso terapéutico , Antivenenos/farmacología , Movimiento Celular , Ácido Clorogénico/farmacología , Femenino , Frutas/química , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Ratones Endogámicos BALB C , Fenoles/uso terapéutico , Extractos Vegetales/uso terapéutico , Neumonía/inducido químicamente , Neumonía/patología , Edema Pulmonar/inducido químicamente , Edema Pulmonar/tratamiento farmacológico , Edema Pulmonar/patología , Rutina/farmacología
7.
Int J Mol Sci ; 18(11)2017 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-29137120

RESUMEN

Scorpions of the genus Tityus are responsible for the majority of envenomation in Brazil, the Tityus serrulatus species being the most common and dangerous in South America. In this approach, we have investigated the ability of the aqueous extract from the leaves of Aspidosperma pyrifolium in reducing carrageenan-induced inflammation and the inflammation induced by T. serrulatus envenomation in mice. We also evaluated the cytotoxic effects of this extract, using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl-2H-tetrazolium (MTT) assay and the results revealed that the extract is safe. Analysis by High Performance Liquid Chromatography coupled with Diode Array Detector (HPLC-DAD) and Liquid Chromatography Coupled with Mass Spectrometry with Diode Array Detection (LC-DAD-MS) showed one major chemical component, the flavonoid rutin and phenolics compounds. For in vivo studies in carrageenan-induced peritonitis model, mice received extracts, dexamethasone, rutin or saline, before administration of carrageenan. For venom-induced inflammation model, animals received T. serrulatus venom and were, simultaneously, treated with extracts, antivenom, rutin or saline. The extract and rutin showed a reduction in the cell migration into the peritoneal cavity, and in the same way the envenomated animals also showed reduction of edema, inflammatory cell infiltration and vasodilation in lungs. This is an original study revealing the potential action of A. pyrifolium against inflammation caused by Tityus serrulatus venom and carrageenan, revealing that this extract and its bioactive molecules, specifically rutin, may present potential anti-inflammatory application.


Asunto(s)
Antiinflamatorios/uso terapéutico , Aspidosperma/química , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Células 3T3 , Animales , Antiinflamatorios/farmacología , Carragenina , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Inflamación/patología , Cinética , Pulmón/efectos de los fármacos , Pulmón/patología , Espectrometría de Masas , Ratones , Ratones Endogámicos BALB C , Peritonitis/complicaciones , Peritonitis/patología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Rutina/farmacología , Venenos de Escorpión , Factores de Tiempo
8.
Artículo en Inglés | MEDLINE | ID: mdl-28904556

RESUMEN

Snakebites are a serious problem in public health due to their high morbimortality. Most of snake venoms produce intense local tissue damage, which could lead to temporary or permanent disability in victims. The available specific treatment is the antivenom serum therapy, whose effectiveness is reduced against these effects. Thus, the search for complementary alternatives for snakebite treatment is relevant. There are several reports of the popular use of medicinal plants against snakebites worldwide. In recent years, many studies have been published giving pharmacological evidence of benefits of several vegetal species against local effects induced by a broad range of snake venoms, including inhibitory potential against hyaluronidase, phospholipase, proteolytic, hemorrhagic, myotoxic, and edematogenic activities. In this context, this review aimed to provide an updated overview of medicinal plants used popularly as antiophidic agents and discuss the main species with pharmacological studies supporting the uses, with emphasis on plants inhibiting local effects of snake envenomation. The present review provides an updated scenario and insights into future research aiming at validation of medicinal plants as antiophidic agents and strengthens the potentiality of ethnopharmacology as a tool for design of potent inhibitors and/or development of herbal medicines against venom toxins, especially local tissue damage.

9.
Chemosphere ; 177: 93-101, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28284120

RESUMEN

Phytol (PYT) is a diterpenoid having important biological activity. However, it is a water non-soluble compound. This study aims to prepare PYT nanoemulsion (PNE) and evaluation of toxic, cytotoxic and genotoxic activities of PYT and PNE. For this, the PNE was prepared by the phase inversion method. The cytotoxicity test was performed in Artemia salina, while toxicity, cytotoxicity and genotoxicity in Allium cepa at concentrations of 2, 4, 8 and 16 mM. Potassium dichromate and copper sulfate were used as positive controls for the tests of A. salina and A. cepa, respectively. In addition, an adaptation response was detected in A. cepa by using the comet assay. The results suggest that both PYT and PNE exhibited toxic and cytotoxic effects at 4-16 mM in either test system, while genotoxicity at 2-16 mM in A. cepa. PNE exhibited more toxic, cytotoxic and genotoxic effects at 8 and 16 mM than the PYT. However, both PYT and PNE at 2 and 4 mM decreased the index and frequency of damage in A. cepa after 48 and 72 h, suggesting a possible adaptation response or DNA damage preventing capacity. Nanoemulsified PYT (PNE) may readily cross the biological membranes with an increase in bioavailability and produce more toxic, cytotoxic and genotoxic effects in the used test systems.


Asunto(s)
Artemia/crecimiento & desarrollo , Daño del ADN/efectos de los fármacos , Nanopartículas/toxicidad , Cebollas/citología , Fitol/toxicidad , Animales , Artemia/efectos de los fármacos , Ensayo Cometa , Emulsiones/química , Emulsiones/toxicidad , Nanopartículas/química , Cebollas/efectos de los fármacos
10.
Biomed Res Int ; 2016: 6101742, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27847818

RESUMEN

Snakebites are a serious worldwide public health problem. In Brazil, about 90% of accidents are attributed to snakes from the Bothrops genus. The specific treatment consists of antivenom serum therapy, which has some limitations such as inability to neutralize local effects, difficult access in some regions, risk of immunological reactions, and high cost. Thus, the search for alternative therapies to treat snakebites is relevant. Jatropha mollissima (Euphorbiaceae) is a medicinal plant popularly used in folk medicine as an antiophidic remedy. Therefore, this study aims to evaluate the effect of the aqueous leaf extract from J. mollissima on local effects induced by Bothrops venoms. High Performance Liquid Chromatography with Diode Array Detection analysis and Mass Spectrometry analysis of aqueous leaf extract confirmed the presence of the flavonoids isoschaftoside, schaftoside, isoorientin, orientin, vitexin, and isovitexin. This extract, at 50-200 mg/kg doses administered by intraperitoneal route, showed significant inhibitory potential against local effects induced by Bothrops erythromelas and Bothrops jararaca snake venoms. Local skin hemorrhage, local edema, leukocyte migration, and myotoxicity were significantly inhibited by the extract. These results demonstrate that J. mollissima extract possesses inhibitory potential, especially against bothropic venoms, suggesting its potential as an adjuvant in treatment of snakebites.


Asunto(s)
Bothrops , Venenos de Crotálidos/envenenamiento , Euphorbiaceae/química , Extractos Vegetales/administración & dosificación , Mordeduras de Serpientes/inducido químicamente , Mordeduras de Serpientes/tratamiento farmacológico , Animales , Antivenenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Extracción Líquido-Líquido , Masculino , Ratones , Fitoterapia/métodos , Hojas de la Planta/química , Plantas Medicinales/química , Resultado del Tratamiento , Agua/química
11.
BMC Complement Altern Med ; 16: 275, 2016 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-27496015

RESUMEN

BACKGROUND: Hancornia speciosa Gomes (Apocynaceae), popularly known as "mangabeira," has been used in folk medicine to treat inflammatory disorders, hypertension, dermatitis, diabetes, liver diseases and gastric disorders. Although the ethnobotany indicates that its fruits can be used for the treatment of ulcers and inflammatory disorders, only few studies have been conducted to prove such biological activities. This study investigated the anti-inflammatory properties of the aqueous extract of the fruits of H. speciosa Gomes as well as its bioactive compounds using in vivo experimental models. METHODS: The bioactive compounds were identified by High Performance Liquid Chromatography coupled with diode array detector (HPLC-DAD) and Liquid Chromatography coupled with Mass Spectrometry (LC-MS). The anti-inflammatory properties were investigated through in vivo tests, which comprised xylene-induced ear edema, carrageenan-induced peritonitis and zymosan-induced air pouch. The levels of IL-1ß, IL-6, IL-12 and TNF-α were determined using ELISA. RESULTS: Rutin and chlorogenic acid were identified in the extract as the main secondary metabolites. In addition, the extract as well as rutin and chlorogenic acid significantly inhibited the xilol-induced ear edema and also reduced the cell migration in both carrageenan-induced peritonitis and zymosan-induced air pouch models. Reduced levels of cytokines were also observed. CONCLUSION: This is the first study that demonstrated the anti-inflammatory activity of the extract of H. speciosa fruits against different inflammatory agents in animal models, suggesting that its bioactive molecules, especially rutin and chlorogenic acid are, at least in part, responsible for such activity. These findings support the widespread use of Hancornia speciosa in popular medicine and demonstrate that its aqueous extract has therapeutical potential for the development of herbal drugs with anti-inflammatory properties.


Asunto(s)
Antiinflamatorios/farmacología , Apocynaceae/química , Ácido Clorogénico/farmacología , Frutas/química , Extractos Vegetales/farmacología , Rutina/farmacología , Animales , Antiinflamatorios/química , Ácido Clorogénico/química , Edema , Femenino , Inflamación/metabolismo , Interleucinas/análisis , Masculino , Ratones , Ratones Endogámicos BALB C , Peritonitis , Extractos Vegetales/química , Rutina/química
12.
J Ethnopharmacol ; 192: 225-235, 2016 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-27448455

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea asarifolia (Desr.) Roem. and Schult.(Convolvulaceae), popularly known as salsa or salsa-brava, is a plant of which the decoction of leaves is used in folk medicine to treat various inflammatory disorders such of dermatitis, scabies, symptoms of syphilis, skin ulcers and external wounds. However, little is known about possible compounds and mechanisms of action of the plant to support the activities reported by popular use. AIM OF THE STUDY: The study aimed to identify bioactive molecules present in the crude extract of I. asarifolia leaves and investigate the anti-inflammatory potential of this extract in different experimental in vivo models to improve the understanding on that activity. MATERIAL AND METHODS: Aqueous extract of I. asarifolia leaves was prepared by decoction (1:10 m/v) and its chromatographic profile was obtained by high performance liquid chromatography coupled with diode array detector (HPLC-DAD) and liquid chromatography diode array detector coupled with mass spectrometry (LC-DAD-MS). The potential anti-inflammatory activity of the extract was assessed using the following in vivo models: xylene-induced ear edema (20, 30 and 40mg/kg), evaluating the degree of edema formation; carrageenan-induced peritonitis (10, 20 and 30mg/kg), evaluating leukocyte migration and cytokine levels (IL-1ß, IL-6, IL-12 and TNF-α) at 4h; zymosan-induced air pouch inflammation (20, 30 and 40mg/kg), evaluating the kinetics of leukocyte migration by total and differential counts at 6, 24 and 48h. The same tests were conducted using pure compounds identified in the aqueous extract from I. asarifolia leaves in different doses for each experimental model. RESULTS: The compounds identified in the aqueous extract of I. asarifolia leaves by HPLC-DAD and LC-DAD-MS were rutin, chlorogenic acid and caffeic acid. The extract significantly reduced ear edema induced by xylene (81%, 85% and 86% for doses of 20, 30 and 40mg/kg, respectively, p<0.001), as well as cell migration in experimental models of peritonitis (70%, 78% and 83% for doses of 10, 20 and 30mg/kg, respectively, p<0.001) and air pouch inflammation (58%, 67% and 53% for doses of 20, 30 and 40mg/kg, respectively, p<0.001). In addition, the extract demonstrated the ability to significantly inhibit the production of cytokines IL-1ß, IL-6, IL-12 and TNF-α (p<0.001). The secondary metabolites tested (rutin, chlorogenic acid and caffeic acid) also showed the ability to significantly (p<0.001) decrease the parameters analyzed above. CONCLUSION: This is the first study to identify and confirm these phenolic compounds in I. asarifolia leaves extract and to suggest that these compounds contribute to the anti-inflammatory activity in vivo, as reported by ethnomedicinal use of this plant. Through the different experimental models performed, we can conclude that the results obtained with the aqueous extract from I. asarifolia leaves support its popular use for the treatment of inflammatory disorders.


Asunto(s)
Antiinflamatorios/farmacología , Edema/prevención & control , Inflamación/prevención & control , Ipomoea/química , Peritonitis/prevención & control , Fenoles/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Animales , Antiinflamatorios/aislamiento & purificación , Carragenina , Quimiotaxis de Leucocito/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Citocinas/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Edema/metabolismo , Femenino , Inflamación/inducido químicamente , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Recuento de Leucocitos , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Espectrometría de Masas , Ratones Endogámicos BALB C , Peritonitis/inducido químicamente , Peritonitis/metabolismo , Fenoles/aislamiento & purificación , Fitoterapia , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Factores de Tiempo , Xilenos , Zimosan
13.
BMC Complement Altern Med ; 14: 405, 2014 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-25328027

RESUMEN

BACKGROUND: Jatropha gossypiifolia L. (Euphorbiaceae) is a medicinal plant largely used in folk medicine. Teas from the leaves are popularly used as an antithrombotic agent and the branches are frequently employed as a "thick blood" agent. Considering that the anticoagulant activity associated with antioxidant properties could be beneficial for various cardiovascular diseases, this study's aim is the evaluation of anticoagulant and antioxidant activities of J. gossypiifolia leaves, seeking new therapeutic purposes for this plant. METHODS: The aqueous leaf crude extract (CE) was prepared by decoction and was fractionated by liquid-liquid partition with solvents of increasing polarity. The phytochemical analysis was performed by thin layer chromatography (TLC) and by the spectrophotometric quantification of sugars, proteins and phenolic compounds. The anticoagulant activity was evaluated by prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests. The capacity to act in the fibrinolytic system (fibrinolytic and fibrinogenolytic activities) was also assessed. The antioxidant activity was evaluated by total antioxidant capacity, reducing power, copper chelating activity, iron chelating activity, hydroxyl radical scavenging activity and superoxide radical scavenging assays. The potential toxicity was evaluated using hemolytic assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay on HEK-293 cells. RESULTS: CE showed significant anticoagulant activity in aPTT test, while no action was observed in PT test, suggesting a preferential action toward the intrinsic and/or common pathway of coagulation. No effect was observed in the fibrinolytic system. Using the aPTT test, it was observed that the residual aqueous (RA) fraction was the most active, being two times more active than CE. RA presented very significant antioxidant activity in all models tested comparable to or even higher than CE. Regarding the safety, CE and RA did not produce significant cytotoxicity in both tests employed. Phytochemical analysis revealed the presence of alkaloids, flavonoids, proteins, tannins, steroids and/or terpenoids and sugars. CONCLUSIONS: CE and RA possessed significant anticoagulant and antioxidant activity and absence of cytotoxic effect in vitro, thus showing the potential of the plant, especially RA fraction, as a new source of bioactive molecules for therapeutic purposes, with particular emphasis on the treatment of cardiovascular diseases.


Asunto(s)
Anticoagulantes/farmacología , Antioxidantes/farmacología , Jatropha/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Anticoagulantes/química , Antioxidantes/química , Eritrocitos/efectos de los fármacos , Flavonoides/química , Flavonoides/farmacología , Células HEK293 , Humanos , Medicina Tradicional , Extractos Vegetales/química , Plantas Medicinales/química , Tiempo de Protrombina
14.
Biomed Res Int ; 2014: 378235, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25013776

RESUMEN

Scorpion bite represents a significant and serious public health problem in certain regions of Brazil, as well as in other parts of the world. Inflammatory mediators are thought to be involved in the systemic and local immune response induced by Tityus serrulatus scorpion envenomation. The aim of this study was to evaluate the effect of extracts of Mimosa tenuiflora on model envenomation. In mice, the envenomation model is induced by Tityus serrulatus venom. Previous treatment of mice with fractions from M. tenuiflora was able to suppress the cell migration to the peritoneal cavity. The treatment of mice with M. tenuiflora extracts also decreased the levels of IL-6, IL-12, and IL-1ß. We concluded that the administration of the extract and fractions resulted in a reduction in cell migration and showed a reduction in the level of proinflammatory cytokines. This study demonstrates, for the first time, the anti-inflammatory effect of aqueous extract from the Mimosa tenuiflora plant on T. serrulatus venom.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Venenos de Escorpión/toxicidad , Animales , Brasil , Humanos , Inflamación/inducido químicamente , Interleucina-12/biosíntesis , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , Ratones , Mimosa/química , Extractos Vegetales/química , Escorpiones/patogenicidad
15.
J Ethnopharmacol ; 153(3): 890-5, 2014 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-24704487

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Envenoming caused by scorpion sting is a serious public health problem. In Brazil, 13,038 accidents caused by venomous animals have been reported. Of this total, 53% of the cases and 14 deaths were caused by scorpions. Furthermore, Tityus serrulatus (Buthidae) is the most dangerous scorpion due to the high toxicity of its venom. The treatment is the common supportive therapy and the serum therapy, but some people do not have access to both therapies and seek healing through the use of medical plants. AIM OF THE STUDY: This study evaluated the ability of the crude extract and fractions from the leaves of Ipomoea asarifolia in neutralizing the main biological effects caused by Tityus serrulatus envenoming in mice. MATERIALS AND METHODS: BALB/c mice were pretreated (i.v.) with 100 µλ of aqueous extracts and fractions dichloromethane, ethyl acetate, and n-butanol (CH2Cl2, EtOAc, and n-BuOH, respectively) of Ipomoea asarifolia, rutin or saline. Then, the animals received 100 µλ (i.p.) of venom of Tityus serrulatus (0.8 mg/kg). After six hours, the peritoneal lavage was performed with PBS and the number cells were determined using a Neubauer chamber. The supernatants were collected for determination of cytokines, such as IL-6, IL-12, and IL-1ß. RESULTS: The aqueous extract, fractions and rutin, at all doses, significantly reduced cell migration, which was endorsed by the reduction of the levels of certain cytokines. CONCLUSION: This is the first study that demonstrated the potential effect of Ipomoea asarifolia against inflammation caused by Tityus serrulatus venom, suggesting that these extracts and/or their bioactive molecules, especially the flavonoid rutin, have potential use in the therapy of this envenomation.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antídotos/uso terapéutico , Ipomoea , Extractos Vegetales/uso terapéutico , Rutina/uso terapéutico , Venenos de Escorpión/toxicidad , Células 3T3 , Animales , Antiinflamatorios/farmacología , Antídotos/farmacología , Movimiento Celular/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Fitoterapia , Extractos Vegetales/farmacología , Hojas de la Planta , Rutina/farmacología , Escorpiones
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