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1.
Toxicol In Vitro ; 90: 105609, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37164183

RESUMO

Salix babylonica L. is a species of the willow tree. Insulinoma is a tumor originating from pancreatic beta cells. This study aims to research the effect of different fractions of Salix babylonica L. leaf extract on INS-1 cells for treating pancreatic tumors. Cell death occurred at lower doses in the EtOAc fraction. The cells are functional in the BuOH fraction but not in EtOAc and H2O fractions. The EtOAc fraction has a higher percentage of necrosis and ROS. INS1, INS2, and AKT gene expressions in the H2O fraction, GLUT2, IR, HSP70 gene expressions, and WNT4 protein levels increased in the BuOH fraction. HSP90 gene expression, Beta-actin, GAPDH, insulin, HSP70, HSP90, HSF1, Beta-Catenin, and WNT7A protein levels were decreased, while IR immunolabelling intensity increased in both fractions. Ca+2, K+, Na+, and CA-19-9 in the cell, Ca+2 and K+ in secretion increased. The secondary metabolites in the EtOAc fraction cause more damage in INS-1 cells. Since the water fraction also causes the cells to die in high doses, cell function is damaged. The secondary metabolites in the BuOH fraction kill INS-1 cells with less damage. This makes the BuOH fraction of Salix babylonica L. more valuable.


Assuntos
Insulinoma , Neoplasias Pancreáticas , Salix , Salix/metabolismo , Extratos Vegetais , Neoplasias Pancreáticas/tratamento farmacológico , Insulina/metabolismo
2.
Curr Pharm Biotechnol ; 21(8): 681-701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31820684

RESUMO

BACKGROUND: The role of Fe+2, Cu+2 and Zn+2 in facilitating aggregation of Amyloid ß (Aß) and consequently, the progression of Alzheimer's disease (AD) is well established. OBJECTIVE: Development of non-toxic metal chelators is an emerging era in the treatment of AD, in which complete success has not been fully achieved. The purpose of this study was to determine plant extracts with high metal chelator and to encapsulate them in nano-micellar systems with the ability to pass through the Blood Brain Barrier (BBB). METHODS: Extracts of 36 different Anatolian plants were prepared, total phenolic and flavonoid contents were determined, and the extracts with high content were examined for their Fe+2, Cu+2 and Zn+2 chelating activities. Apolipoprotein E4 (Apo E) decorated nano-formulations of active extracts were prepared using Poly (Lactide-co-Glycolide) (PLGA) (final product ApoEPLGA) to provide BBB penetrating property. RESULTS: Verbascum flavidum aqueous extract was found as the most active sample, incubation of which, with Aß before and after metal-induced aggregation, resulted in successful inhibition of aggregate formation, while re-solubilization of pre-formed aggregates was not effectively achieved. The same results were obtained using ApoEPLGA. CONCLUSION: An optimized metal chelator nano-formulation with BBB penetrating ability was prepared and presented for further in-vivo studies.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Quelantes/farmacologia , Portadores de Fármacos/química , Metais Pesados/metabolismo , Nanopartículas/química , Extratos Vegetais/farmacologia , Agregados Proteicos/efeitos dos fármacos , Apolipoproteína E4/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quelantes/administração & dosagem , Quelantes/isolamento & purificação , Quelantes/toxicidade , Composição de Medicamentos , Fibroblastos/efeitos dos fármacos , Humanos , Metais Pesados/toxicidade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Cultura Primária de Células , Verbascum/química
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