RESUMO
Plant lectins are carbohydrate-binding proteins, which can interact with cell surfaces to initiate anti-inflammatory pathways, as well as immunomodulatory functions. Here, we have extracted, purified and part-characterized the bioactivity of Jacalin, Frutalin, DAL and PNA, before evaluating their potential for wound healing in cultured human skin fibroblasts. Only Frutalin stimulated fibroblast migration in vitro, prompting further studies which established its low cytotoxicity and interaction with TLR4 receptors. Frutalin also increased p-ERK expression and stimulated IL-6 secretion. The in vivo potential of Frutalin for wound healing was then assessed in hybrid combination with the polysaccharide galactomannan, purified from Caesalpinia pulcherrima seeds, using both hydrogel and membrane scaffolds formulations. Physical-chemical characterization of the hybrid showed that lectin-galactomannan interactions increased the pseudoplastic behaviour of solutions, reducing viscosity and increasing Frutalin's concentration. Furthermore, infrared spectroscopy revealed -OH band displacement, likely caused by interaction of Frutalin with galactose residues present on galactomannan chains, while average membrane porosity was 100⯵m, sufficient to ensure water vapor permeability. Accelerated angiogenesis and increased fibroblast and keratinocyte proliferation were observed with the optimal hybrid recovering the lesioned area after 11â¯days. Our findings indicate Frutalin as a biomolecule with potential for tissue repair, regeneration and chronic wound healing.
Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Galectinas/química , Hidrogéis/química , Mananas/química , Membranas Artificiais , Cicatrização/efeitos dos fármacos , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Linhagem Celular , Galactose/análogos & derivados , Humanos , Camundongos , Modelos Moleculares , Conformação Proteica , Receptor 4 Toll-Like/química , Receptor 4 Toll-Like/metabolismoRESUMO
This study aimed to evaluate a microemulsion system (ME) containing phenobarbital in epilepsy model induced by pilocarpine in rats and to oxidative stress and histologic lesions in hippocampus. The microemulsion was applied to the shaved back of Wistar rats. The animals were divided into the following groups: control group (P400); ME50 40mg/kg, topically-t.p.; ME100, 40mg/kg, t.p.; EM50, 40mg/kg, t.p.; phenobarbital solution 40mg/kg (PS), oral. After 60min, behavioral changes were evaluated for 1h in the model of epileptical crisis induced by pilocarpine. Phenobarbital in microemulsion was able to increase the latency for status epilepticus (SE) (p<0.05), decrease the number of epileptical crisis (ME50: p<0.001; ME100: p<0.01) and decrease mortality rate by 80% compared to P400. In EM50 and PS groups, deaths were decreased by 53.3% and 100% respectively. The ME50 and ME100 groups were able to reduce oxidative stress in experimental animals when compared to the P400. The microemulsion was still capable of reducing neuronal damage in the hippocampal areas. The results of this study come in an innovative way, demonstrating the ability of transdermal ME50 and ME100 to reduce pilocarpine-induced epileptical crisis, oxidative stress, besides neuronal damages.
Assuntos
Anticonvulsivantes/administração & dosagem , Antioxidantes/administração & dosagem , Fenobarbital/administração & dosagem , Pilocarpina/farmacologia , Convulsões/tratamento farmacológico , Administração Cutânea , Animais , Anticonvulsivantes/uso terapêutico , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Emulsões/administração & dosagem , Feminino , Hipocampo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenobarbital/uso terapêutico , Ratos , Ratos Wistar , Convulsões/induzido quimicamenteRESUMO
Farnesol, a sesquiterpene alcohol, has been shown to have antioxidant and anti-inflammatory properties. Recent studies have found that antioxidant compounds may exert a certain protective effect against neurotoxicity. The objective of this study was to evaluate the antinociceptive activity of farnesol (FAR) and its neurotoxic effects on the brains of adult mice. In this study, two mouse models of analgesia were used to evaluate FAR at doses of 50, 100, and 200 mg/kg, injected intraperitoneally (i.p.). In the acetic acid-induced writhing test, a significant decrease was found in the number of contortions in the FAR-treated mice at doses of 50, 100, and 200 mg/kg. FAR was also found to inhibit the licking response in the injected paw at doses of 100 and 200 mg/kg (i.p.) in the first (0-5 min) and second phases (15-30 min) of the formalin test. To evaluate neurotoxic effects, Swiss mice were treated with 0.9% saline (i.p., control group), 0.05 Tween 80 dissolved in 0.9% saline (i.p., vehicle group), and FAR 50, 100, or 200 mg/kg, i.p. Following treatment, all groups were observed for 72 h. In the FAR 200-mg group, 16% of the animals suffered brain injury that affected 12% of the area of the hippocampus. No lesions were found in the hippocampal and striatal regions of the brain in any of the animals treated with the 50 and 100 mg/kg doses of FAR. In conclusion, FAR exerts an antinociceptive effect with no significant neurotoxicity in the brains of adult mice.