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1.
Int J Mol Sci ; 25(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39063085

RESUMO

The genus Sambucus, mainly Sambucus nigra, has emerged as a valuable source of bioactive compounds with potential neuroprotective properties. This review explores the antioxidant, anti-inflammatory, and neuroregenerative effects of Sambucus-derived compounds and their implications for brain health and cognitive function. In vitro studies have demonstrated the ability of Sambucus extracts to mitigate oxidative stress, modulate inflammatory responses, and promote neural stem cell proliferation and differentiation. In vivo studies using animal models of neurodegenerative diseases, such as Alzheimer's and Parkinson's, have shown that Sambucus compounds can improve cognitive function, motor performance, and neuronal survival while attenuating neuroinflammation and oxidative damage. The neuroprotective effects of Sambucus are primarily attributed to its rich content of polyphenols, particularly anthocyanins, which exert their benefits through multiple mechanisms, including the modulation of signaling pathways involved in inflammation, apoptosis, mitochondrial function, and oxidative stress. Furthermore, the potential of Sambucus as a functional food ingredient is discussed, highlighting its application in various food products and the challenges associated with the stability and bioavailability of its bioactive compounds. This review provides a comprehensive overview of the current state of research on the neuroprotective potential of Sambucus and its derivatives, offering valuable insights for the development of dietary strategies to promote brain health and prevent age-related cognitive decline.


Assuntos
Anti-Inflamatórios , Antioxidantes , Alimento Funcional , Fármacos Neuroprotetores , Extratos Vegetais , Sambucus , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Sambucus/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Estresse Oxidativo/efeitos dos fármacos
2.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674113

RESUMO

The diterpene 7α-acetoxy-6ß-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6ß-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.


Assuntos
Diterpenos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Plectranthus , Humanos , Plectranthus/química , Diterpenos/química , Diterpenos/farmacologia , Diterpenos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Simulação por Computador , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos
3.
ACS Omega ; 9(32): 34905-34917, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39157076

RESUMO

A method for the synthesis of a new SERS substrate-anisotropic silver nanoparticles using mellitic acid as a new capping agent is presented. The synthesis is free of toxic substances and does not require special temperature or lighting conditions. Moreover, it is fast, easy, and inexpensive. Depending on the concentration of silver ions and nanoparticle seeds, four different colloids were obtained, representing the evolution of nanoparticle growth along different paths from the first common stage. One of the synthesized colloids consists mainly of triangular nanoplates, while the other consists of polyhedral NPs. The analysis of the synthesis process together with the observation of TEM images and UV-vis extinction spectra enabled the proposal of the mechanism of interaction of mellitic acid molecules as the capping agent. The ability of mellitic acid molecules to form a hydrogen bond network, together with a ratio of silver ions to the mellitic acid concentration, turned out to be crucial for determining the shape of the NPs. All obtained colloids strongly enhance the Raman spectra of analyte molecules, thus proving their applicability as efficient new SERS substrates. For the one that enhanced the spectra the most, the detection limit was set at 10-9 M. Using it as a SERS substrate enables the identification of a trace amount of a designer drug, i.e., 4-chloromethcathinone (4-CMC, clephedrone). For the first time, SERS spectra of this substance, illegal in many countries, are presented.

4.
Cancers (Basel) ; 16(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38201643

RESUMO

Due to the impact of nodal metastasis on colon cancer prognosis, adequate regional lymph node resection and accurate pathological evaluation are required. The ratio of metastatic to examined nodes may bring an additional prognostic value to the actual staging system. This study analyzes the identification of factors influencing a high lymph node yield and its impact on survival. The lymph node ratio was determined in patients with fewer than 12 or at least 12 evaluated nodes. The study included patients after radical colon cancer resection in UICC stages II and III. For the lymph node ratio (LNR) analysis, node-positive patients were divided into four categories: i.e., LNR 1 (<0.05), LNR 2 (≥0.05; <0.2), LNR 3 (≥0.2; <0.4), and LNR 4 (≥0.4), and classified into two groups: i.e., those with <12 and ≥12 evaluated nodes. The study was conducted on 7012 patients who met the set criteria and were included in the data analysis. The mean number of examined lymph nodes was 22.08 (SD 10.64, median 20). Among the study subjects, 94.5% had 12 or more nodes evaluated. These patients were more likely to be younger, women, with a lower ASA classification, pT3 and pN2 categories. Also, they had no risk factors and frequently had a right-sided tumor. In the multivariate analysis, a younger age, ASA classification of II and III, high pT and pN categories, absence of risk factors, and right-sided location remained independent predictors for a lymph node yield ≥12. The univariate survival analysis of the entire cohort demonstrated a better five-year overall survival (OS) in patients with at least 12 lymph nodes examined (68% vs. 63%, p = 0.027). The LNR groups showed a significant association with OS, reaching from 75.5% for LNR 1 to 33.1% for LNR 4 (p < 0.001) in the ≥12 cohort, and from 74.8% for LNR2 to 49.3% for LNR4 (p = 0.007) in the <12 cohort. This influence remained significant and independent in multivariate analyses. The hazard ratios ranged from 1.016 to 2.698 for patients with less than 12 nodes, and from 1.248 to 3.615 for those with at least 12 nodes. The LNR allowed for a more precise estimation of the OS compared with the pN classification system. The metastatic lymph node ratio is an independent predictor for survival and should be included in current staging and therapeutic decision-making processes.

5.
Brain Pathol ; : e13255, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504469

RESUMO

Premature birth or complications during labor can cause temporary disruption of cerebral blood flow, often followed by long-term disturbances in brain development called hypoxic-ischemic (HI) encephalopathy. Diffuse damage to the white matter is the most frequently detected pathology in this condition. We hypothesized that oligodendrocyte progenitor cell (OPC) differentiation disturbed by mild neonatal asphyxia may affect the viability, maturation, and physiological functioning of oligodendrocytes. To address this issue, we studied the effect of temporal HI in the in vivo model in P7 rats with magnetic resonance imaging (MRI), microscopy techniques and biochemical analyses. Moreover, we recreated the injury in vitro performing the procedure of oxygen-glucose deprivation on rat neonatal OPCs to determine its effect on cell viability, proliferation, and differentiation. In the in vivo model, MRI evaluation revealed changes in the volume of different brain regions, as well as changes in the directional diffusivity of water in brain tissue that may suggest pathological changes to myelinated neuronal fibers. Hypomyelination was observed in the cortex, striatum, and CA3 region of the hippocampus. Severe changes to myelin ultrastructure were observed, including delamination of myelin sheets. Interestingly, shortly after the injury, an increase in oligodendrocyte proliferation was observed, followed by an overproduction of myelin proteins 4 weeks after HI. Results verified with the in vitro model indicate, that in the first days after damage, OPCs do not show reduced viability, intensively proliferate, and overexpress myelin proteins and oligodendrocyte-specific transcription factors. In conclusion, despite the increase in oligodendrocyte proliferation and myelin protein expression after HI, the production of functional myelin sheaths in brain tissue is impaired. Presented study provides a detailed description of oligodendrocyte pathophysiology developed in an effect of HI injury, resulting in an altered CNS myelination. The described models may serve as useful tools for searching and testing effective of effective myelination-supporting therapies for HI injuries.

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