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1.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38931424

RESUMO

Diabetes, a multifactorial metabolic disorder, demands the discovery of multi-targeting drugs with minimal side effects. This study investigated the multi-targeting antidiabetic potential of quercetin and kaempferol. The druggability and binding affinities of both compounds towards multiple antidiabetic targets were explored using pharmacokinetic and docking software (AutoDock Vina 1.1.2). Our findings showed that quercetin and kaempferol obey Lipinski's rule of five and exhibit desirable ADMET (absorption, distribution, metabolism excretion, and toxicity) profiles. Both compounds showed higher binding affinities towards C-reactive protein (CRP), interleukin-1 (IL-1), dipeptidyl peptidase-4 (DPP-IV), peroxisome proliferator-activated receptor gamma (PPARG), protein tyrosine phosphatase (PTP), and sodium-glucose co-transporter-1 (SGLT-1) compared to metformin (the positive control). Both quercetin and kaempferol inhibited α-amylase activity (in vitro) up to 20.30 ± 0.49 and 37.43 ± 0.42%, respectively. Their oral supplementation significantly reduced blood glucose levels (p < 0.001), improved lipid profile (p < 0.001), and enhanced total antioxidant status (p < 0.01) in streptozotocin-nicotinamide (STZ-NA)-induced diabetic mice. Additionally, both compounds significantly inhibited the proliferation of Huh-7 and HepG2 (cancer cells) (p < 0.0001) with no effect on the viability of Vero cell line (non-cancer). In conclusion, quercetin and kaempferol demonstrated higher binding affinities towards multiple targets than metformin. In vitro and in vivo antidiabetic potential along with the anticancer activities of both compounds suggest promise for further development in diabetes management. The combination of both drugs did not show a synergistic effect, possibly due to their same target on the receptors.

2.
Int J Mol Sci ; 25(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255803

RESUMO

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-ß protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.


Assuntos
Sobrecarga de Ferro , Ferro , Humanos , Sistema Nervoso Central , Encéfalo , Peptídeos beta-Amiloides
3.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361743

RESUMO

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Quitosana/química , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Radiossensibilizantes/farmacologia , Nanomedicina Teranóstica/métodos , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Meios de Contraste/síntese química , Meios de Contraste/farmacologia , Curcumina/química , Curcumina/farmacologia , Sulfato de Dextrana/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Composição de Medicamentos/métodos , Humanos , Cinética , Nanopartículas de Magnetita/ultraestrutura , Oxigênio/química , Oxigênio/farmacologia , Radiossensibilizantes/síntese química
4.
Molecules ; 25(9)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365941

RESUMO

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.


Assuntos
Sistema Nervoso Central , Portadores de Fármacos/química , Hipertermia Induzida , Nanopartículas de Magnetita/química , Nanomedicina Teranóstica/métodos , Animais , Neoplasias Encefálicas/terapia , Sobrevivência Celular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Fenômenos Químicos , Sistemas de Liberação de Medicamentos , Células Endoteliais/metabolismo , Hemólise , Humanos , Hipertermia Induzida/métodos , Campos Magnéticos
5.
Materials (Basel) ; 12(3)2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717431

RESUMO

Magnetic Nanoparticles (MNPs) are of great interest in biomedicine, due to their wide range of applications. During recent years, one of the most challenging goals is the development of new strategies to finely tune the unique properties of MNPs, in order to improve their effectiveness in the biomedical field. This review provides an up-to-date overview of the methods of synthesis and functionalization of MNPs focusing on Iron Oxide Nanoparticles (IONPs). Firstly, synthesis strategies for fabricating IONPs of different composition, sizes, shapes, and structures are outlined. We describe the close link between physicochemical properties and magnetic characterization, essential to developing innovative and powerful magnetic-driven nanocarriers. In conclusion, we provide a complete background of IONPs functionalization, safety, and applications for the treatment of Central Nervous System disorders.

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