RESUMEN
This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. In addition, the toxicity and antioxidant capacities were tested in Artemia salina and rat erythrocytes, respectively. The results suggest that, an acute administration of the IF at doses of 25, 50, 75 and 150â¯mg/kg (intraperitoneal, i.p.) significantly (pâ¯<â¯0.05) reduced the marble burying behavior of the animals as compared to the vehicle group, which demonstrates a calming effect of this chemical. It was observed that, the pre-treatment with flumazenil (2.5â¯mg/kg, i.p.), an antagonist of the gamma-amino butyrinc acid (GABAA) receptor, significantly reversed the marble burying behavioral activity in the animals treated with the IF 150â¯mg/kg dose. Moreover, the reduction in nitrite content and lipid peroxidation levels, while an increased in the reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16â¯mM) did not show toxicity in A. salina but exhibited a prominent antioxidant capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In conclusion, IF exhibited an anxiety-like effect in mice along with a potent antioxidant capacity, and we suppose it may have neuroprotective effects possibly via GABAergic transmission pathway.
Asunto(s)
Ansiolíticos/farmacología , Biomarcadores/metabolismo , Ácidos Cumáricos/farmacología , Estrés Oxidativo/efectos de los fármacos , Ácido gamma-Aminobutírico/metabolismo , Animales , Antioxidantes/metabolismo , Artemia/efectos de los fármacos , Ácido Ascórbico/farmacología , Conducta Animal/efectos de los fármacos , Catalasa/metabolismo , Ácidos Cumáricos/toxicidad , Diazepam/farmacología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Hemólisis/efectos de los fármacos , Hipocampo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Nitritos/metabolismo , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Pruebas de ToxicidadRESUMEN
BACKGROUND: Research on natural bioactive compounds has increased exponentially over the last decades. The discovery of new phytochemicals that possess pharmaceutical properties is useful in the development of therapeutic alternatives. The nerolidol (3,7,11-trimetil-1,6,10-dodecatrien-3-ol or 3,7,11-trimetildodeca-1,6,10-trien-3-ol) has been extensively studied for its therapeutic potential because of its pharmacological activities in the treatment of neurodegenerative diseases. METHOD: All articles and patents regarding nerolidol and its pharmacological properties were revised, focusing mainly on the important properties in the treatment of neurodegenerative diseases. A thorough search in article databases (Science Direct, MEDLINE/PubMed, Scopus and Scielo) and patent database (WIPO, EPO, ESPTO, LATIPAT and INPI) was performed over the course of this study. RESULTS: Several studies stood out for their relevance regarding the treatment of neurodegenerative diseases. Nerolidol demonstrated anticholinesterasic, antioxidant, antinociceptive, anti-inflammatory and anxiolytic activities, thus classifying it as a promising phytochemical for the development of therapeutic drugs. CONCLUSION: Analysis suggested that nerolidol is a promising target for new drugs and treatment of neurodegenerative diseases.
Asunto(s)
Enfermedades Neurodegenerativas/tratamiento farmacológico , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , Analgésicos/química , Analgésicos/farmacología , Analgésicos/uso terapéutico , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/farmacología , Antagonistas Colinérgicos/uso terapéutico , Humanos , Estructura Molecular , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Patentes como Asunto , Fitoquímicos/química , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificaciónRESUMEN
D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E2, and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1ß levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.
Asunto(s)
Analgésicos/farmacología , Antiinflamatorios/farmacología , Edema/tratamiento farmacológico , Monoterpenos/farmacología , Animales , Permeabilidad Capilar/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Monoterpenos Ciclohexánicos , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Mediadores de Inflamación , Masculino , Ratones , Monoterpenos/uso terapéutico , Neutrófilos/citología , Dolor/tratamiento farmacológicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. AIM OF THE STUDY: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors. MATERIALS AND METHODS: Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed. RESULTS: The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D1 complex is up to 1000-fold more favourable than the Cas X-GABAA complex. All ∆G° values obtained for Cas X-D1 complexes were more negative than those seen with Cas X-GABAA complexes. CONCLUSIONS: Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system.
Asunto(s)
Conducta Animal/efectos de los fármacos , Casearia/química , Diterpenos/farmacología , Extractos Vegetales/farmacología , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/aislamiento & purificación , Ansiolíticos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Simulación por Computador , Diazepam/farmacología , Diterpenos/administración & dosificación , Diterpenos/aislamiento & purificación , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Neuronas/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/toxicidadRESUMEN
The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.
Asunto(s)
Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Sesquiterpenos/farmacología , Animales , Hipocampo/fisiología , RatonesRESUMEN
The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P < 0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P < 0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.
RESUMEN
Garcinielliptone FC (GFC), a natural prenylated benzophenone, was extracted from Platonia insignis Mart. (Clusiaceae), a native plant commonly known as bacuri and used in traditional Brazilian medicine for the treatment of skin diseases. The aim of this study was to evaluate the cytotoxic and leishmanicidal effects of GFC using in vitro models. The experimental data demonstrated that the polyisoprenylated benzophenone GFC possesses cytotoxic and leishmanicidal activities.
Asunto(s)
Benzofenonas/química , Clusiaceae/química , Leishmania/efectos de los fármacos , Tripanocidas/química , Tripanocidas/farmacología , Línea Celular Tumoral , Células HT29 , Humanos , TriterpenosRESUMEN
Blood flukes of the genus Schistosoma are the causative agents of human schistosomiasis, a debilitating disease that afflicts over 200 million people worldwide. Praziquantel is the drug of choice but concerns over praziquantel resistance have renewed interest in the search for alternative drug therapies. Carvacrol, a naturally occurring monoterpene phenol and food additive, has been shown high medicinal importance, including antimicrobials activities. The aim of this study was to evaluate in vitro effect of carvacryl acetate, a derivative of carvacrol, on Schistosoma mansoni adult worms. We demonstrated that carvacryl acetate at 6.25 µg/mL has antischistosomal activity, affecting parasite motility and viability. Additionally, confocal laser scanning microscopy pictures revealed morphological alterations on the tegumental surface of worms, where some tubercles appeared to be swollen with numerous small blebs emerging from the tegument around the tubercles. Furthermore, experiments performed using carvacryl acetate at sub-lethal concentrations (ranging from 1.562 to 6.25 µg/mL) showed an inhibitory effect on the daily egg output of paired adult worms. Thus, carvacryl acetate is toxic at high doses, while at sub-lethal doses, it significantly interferes with the reproductive fitness of S. mansoni adult worms. Due to its safety and wide use in the industry, carvacryl acetate is a promising natural product-derived compound and it may represent a step forward in the search for novel anthelmintic agents, at a time when there is an urgent need for novel drugs.