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1.
Biomed Pharmacother ; 179: 117304, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39178813

RESUMO

Nymphaea candida Presl (NC), traditionally used in medicine for heat syndrome-related ailments, possesses antioxidative, anti-inflammatory, hepatoprotective, and neuroprotective properties. This research investigates the antidepressant and neuroprotective effects and mechanisms of Nymphaea candida Presl ethyl acetate (NCEA). Primary components of NCEA were identified as phenolic acids and flavonoids through UPLC-MS/MS analysis. The depression mouse model was induced via intracerebroventricular injection of Lipopolysaccharide (LPS), followed by oral administration of fluoxetine and NCEA for one week. Biochemical assays and HE staining confirmed NCEA's non-toxicity and protective effects on the liver and lungs. NCEA administration mitigated LPS-induced depressive behaviors, decreased IL-1ß, TNF-α levels in the hippocampus, suppressed microglial activation, reduced Iba-1 expression, and increased NA, brain-derived neurotrophic factor (BDNF), and dendritic spine density in the hippocampus. Furthermore, NCEA enhanced cell viability in a CORT-induced PC12 cell model, decreased lactate dehydrogenase (LDH) release rate, total superoxide dismutase (SOD) inhibition rate, intracellular nitric oxide (NO) release, and reduced reactive oxygen species (ROS) production. Our research findings suggest that NCEA exhibits significant antidepressant effects, which may be attributed to its reduction of neuroinflammation, improvement in neurotransmitter levels, neuronal protection, and antioxidative stress properties.


Assuntos
Acetatos , Antidepressivos , Fármacos Neuroprotetores , Extratos Vegetais , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Antidepressivos/farmacologia , Antidepressivos/isolamento & purificação , Camundongos , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Ratos , Acetatos/química , Acetatos/farmacologia , Células PC12 , Depressão/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Modelos Animais de Doenças , Lipopolissacarídeos , Comportamento Animal/efeitos dos fármacos
2.
ACS Chem Neurosci ; 15(9): 1893-1903, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38613492

RESUMO

Depression is a common mental disorder. In recent years, more and more attention has been paid to depression and its etiology and pathogenesis. This review aims to explore the neuroprotective and antidepressant effects of hop components. By establishing an in vitro cell damage model using PC12 cells induced by corticosterone (CORT) and an in vivo depression model through the intracranial injection of lipopolysaccharide (LPS) in mice, hop ethyl acetate extract (HEA) was used to study the protective effect and mechanism of HEA on neuronal cells in vitro and the antidepression effect and mechanism in vivo. The results showed that HEA increased the survival and decreased the rate of lactate dehydrogenase (LDH) release, apoptosis, and the ROS and NO content of CORT-induced PC12 cells. HEA alleviated depressive-like behavior, neuroinflammation, reduction of norepinephrine, and dendritic spines induced by intracerebroventricular injection of LPS in mice and increases the expression levels of BDNF, SNAP 25, and TrkB proteins without any significant side effects or toxicity. Hops demonstrated significant comprehensive utilization value, and this work provided an experimental basis for the role of hops in the treatment of depression and provided a basis for the development of HEA for antidepressant drugs or dietary therapy products.


Assuntos
Acetatos , Antidepressivos , Corticosterona , Depressão , Humulus , Fármacos Neuroprotetores , Extratos Vegetais , Animais , Células PC12 , Camundongos , Depressão/tratamento farmacológico , Extratos Vegetais/farmacologia , Acetatos/farmacologia , Antidepressivos/farmacologia , Ratos , Fármacos Neuroprotetores/farmacologia , Masculino , Humulus/química , Lipopolissacarídeos/farmacologia , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos
3.
ACS Nano ; 18(18): 11688-11702, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38665009

RESUMO

Designing an efficient nanocarrier to target multiple types of cancer remains a major challenge in the development of cancer nanomedicines. The majority of systemically administered nanoparticles (NPs) are rapidly cleared by the liver, resulting in poor tumor-targeting efficiency and severe side effects. Here, we present a delicately tailored design and synthesis of fluorescent bottle-brush polymers and screen nine derived NPs, each varying in size and surface coatings, for tumor imaging and targeted delivery. Our optimized polymer bearing (oligo(ethylene glycol) methyl ether methacrylate) in the side chains shows reduced macrophage uptake, prolonged blood-circulation time (up to 27 h), and exceptionally high accumulation in the tumor compared to the liver, elucidating an immune-evasion-induced tumor-targeting mechanism. High tumor accumulation significantly improved the antitumor efficacy. The outstanding tumor-targeting ability has been further validated across five distinct tumor models, including orthotopic glioblastoma and pancreatic cancer, which demonstrate the universality of our polymeric nanocarrier for tumor-targeting delivery.


Assuntos
Polímeros , Animais , Humanos , Camundongos , Polímeros/química , Nanopartículas/química , Nanomedicina Teranóstica , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Metacrilatos/química , Polietilenoglicóis/química
4.
Exp Ther Med ; 26(2): 397, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37533491

RESUMO

The present study investigated the expression level of microRNA (miR)-137 in glioma tissues and cell lines and explored its potential diagnostic significance as well as its function effects on glioma cells. miR-137 expression level was detected in glioma tissues using in situ hybridization, and in glioma cell lines using reverse transcription-quantitative PCR (RT-qPCR). The diagnostic significance of miR-137 in glioma was assessed using receiver operating characteristic curve analyses. Quantibody® Human Inflammation Array 1 was used to evaluate the impact of ectopic miR-137 expression on release of cytokines in glioma cell lines. IL-13, TNF-α and IFN-γ levels were detected using ELISA. To confirm that sphingosine kinase 2 (SPHK2) is a target of miR-137, RT-qPCR, western blot analysis and dual-luciferase assay were adopted. The results demonstrated that miR-137 expression was downregulated in both glioma tissues and cell lines. Downregulation of miR-137 was significantly associated with high grade gliomas. Additionally, it was found that overexpression of miR-137 reduced IL-13, but promoted TNFα and IFN-γ production. SPHK2 knockdown inhibited IL-13 release, promoted TNF-α and IFN-γ production. SPHK2 was a direct target of miR-137. Collectively, the results of the present study indicated that miR-137 expression plays a tumor-suppressive role in glioma. It is downregulated in glioma and may promote M1-type TAMs polarization, and may be a diagnostic biomarker and potential therapeutic strategy for glioma treatment in the future.

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