Langassner, Silvana Maria ZucolottoAlves, Jovelina Samara Ferreira2020-01-222019-08-30ALVES, Jovelina Samara Ferreira. Obtenção, caracterização e avaliação da atividade antidepressiva de extrato rico em flavonoides na forma livre e de nanopartículas poliméricas elaborados a partir das folhas de Passiflora edulis fo. flavicarpa (maracujá-amarelo). 2019. 108f. Tese (Doutorado em Ciências da Saúde) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2019.https://repositorio.ufrn.br/jspui/handle/123456789/28346Passiflora species are recognized for synthesizing various flavonoid derivatives with neuroactive and antioxidant properties, which can prevent brain damage caused by depressive disorders. However, due to the low bioavailability, its clinical application is a challenge for pharmaceutical technology. In this context, Passiflora edulis fo. flavicarpa O. Degener (Passifloraceae) species, popularly known as yellow passion fruit has been researched. Thus, the aims of this work are: i. to develop a method for obtaining a flavonoid enriched extract (FRE) from Passiflora edulis fo. flavicarpa leaves; ii. purify and characterize flavonoids from FRE extract; iii. develop a FRE extract-loaded nanoparticle system; iv. evaluate the biocompatibility and antidepressant-like effect of FRE extract and loaded-nanoparticles. Raw material (leaves) were collected in a cultivation and dried to obtain a flavonoid rich extract by optimization of extraction through surface response methodology. FRE was used for isolation of major compounds by HPLC-UV-DAD-Prep. After, a FRE extract-loaded nanoparticle system produced with poly (methyl methacrylate) (PMMA) polymer was developed and characterized by size measurement, zeta potential, encapsulation efficiency, infrared and atomic force microscopy. Furthermore, biocompatibility (through acute oral toxicity model) and antidepressant-like effect (using forced swimming and open field models) were evaluated after oral administration of FRE extract and loaded nanoparticles and isoorientin in in vivo models. Quantitative analysis showed that the FRE has a total flavonoid content of 11.42 mg/g and a isoorientin content of 5.21 mg/g. Thirteen glycosylated flavonoids derived from luteolin, chrysin and apigenin were identified by HPLC-ESI-IT-MS/MS analysis. After, the content of flavonoids vicenin-2 (5.20 mg/g), orientin (0.59 mg/g), vitexin (0.20 m /g) and isovitexin (0.96 mg/g) were evaluated. Physicochemical analysis showed that extract-loaded nanoparticles are spherical, with a zeta potential size of 65.6 nm, high isoorientin encapsulation efficiency (EE = 100%) and that the system remained stable throughout the six months. Histopathological and biochemical analyzes of animals serum and tissues showed the biocompatibility of blank nanoparticles, extract (2 g/kg kg; p.o.) and extract-loaded nanoparticles 5 mg/kg; p.o.). The antidepressant-like effect after acute oral administration of FRE (50 and 100 mg/kg; P <0.01 and P <0.001) and extract-loaded nanoparticles (5 mg/kg; P <0.01) and isoorientin (1 -10 mg / kg, P <0.001) was investigated in the forced swimming test. The results were similar to the nortriptyline antidepressant drug, that showed a reduction of animals immobility time. Thus, the optimization of the extraction method increased the antidepressant potential 10-fold when compared with previous results in the literature. The encapsulation of FRE in PMMA nanoparticles promoted a decrease of 10-fold of dose to maintain the same antidepressant-like effect of free extract. Ultimately, this work described to the first time the antidepressant-like effect of isoorientin, suggesting it as a possible active marker for P. edulis. Our results confirm that extract and extract-loaded nanoparticle obtained from P. edulis leaves are a promising raw material that can be used in the development of an antidepressant herbal medicine.Acesso AbertoPassifloraceaeFitoterápicoMarcadorNanotecnologiaDepressãodoctoralThesisCNPQ::CIENCIAS DA SAUDE