Several natural products have been proven to prevent neurodegenerative disorders by potentiating the action of nerve growth factor (NGF). Among them, secoiridoids have recently attracted interest for their potential use as neuritogenic compounds. A source of these compounds is the root of Gentiana lutea L. used in food products to improve digestion. The aim of this work was to evaluate the neuritogenic activity of methanolic extracts of cultivated, wild and commercial roots of G. lutea using rat pheochromocytoma (PC12) cells. Neuritogenic activity was assessed by xCELLigence real time cell analysis system (RTCA DP), neurite outgrowth image analysis and immunofluorescence staining. Extracts at 12.5 and 25 μg/ml with or without NGF showed a marked stimulation of neuritogenesis, without cytotoxic effects, and their neuritogenic action was synergistic to NGF activity. These results represent the first evidence of the neuritogenic effects of G. lutea and of its potential use as a functional food ingredient

Recent advancements in cancer therapy have led to the development of novel nanoparticle-based drug delivery systems aimed at enhancing the efficacy of chemotherapeutic agents. This study focuses on evaluating aprepitant-loaded PLGA and Eudragit RS 100 nanoparticles for their potential antiangiogenic effects. Characterization studies revealed that aprepitant-loaded nanoparticles exhibited particle sizes ranging from 208.50 to 238.67 nm, with monodisperse distributions (PDI < 0.7) and stable zeta potentials (between − 5.0 and − 15.0 mV). Encapsulation efficiencies exceeding 99% were achieved, highlighting the efficacy of PLGA and Eudragit RS 100 as carriers for aprepitant. Cellular uptake studies demonstrated enhanced internalization of aprepitant-loaded nanoparticles by HUVEC cells compared to free aprepitant, as confirmed by fluorescence microscopy. Furthermore, cytotoxicity assays revealed significant dose-dependent effects of aprepitant-loaded nanoparticles on HUVEC cell viability, with IC₅₀ values at 24 h of 11.9 µg/mL for Eudragit RS 100 and 94.3 µg/mL for PLGA formulations. Importantly, these nanoparticles effectively inhibited HUVEC cell migration and invasion induced by M2c supernatant, as evidenced by real-time cell analysis and gene expression studies. Moreover, aprepitant-loaded nanoparticles downregulated VEGFA and VEGFB gene expressions and reduced VEGFR-2 protein levels in HUVEC cells, highlighting their potential as antiangiogenic agents. Overall, this research underscores the promise of nanoparticle-based aprepitant formulations in targeted cancer therapy, offering enhanced therapeutic outcomes through improved drug delivery and efficacy against angiogenesis.

Parkinson’s disease (PD) is a chronic, progressive, and age-related neurodegenerative disorder characterized by the loss of midbrain dopaminergic neurons caused by the accumulation of free radicals and oxidative stress. Based on the neuroprotective properties of 2-pyrazoline derivatives, in the current work, 1-(phenyl/4-substituted phenyl)-3-(2-furanyl/thienyl)-5-aryl-2-pyrazolines (3a–i, 4a–i) were synthesized via the cyclization of the chalcones (1, 2) with suitable phenylhydrazine hydrochloride derivatives. All these compounds were investigated for their neuroprotective effects using an in vitro 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model of PD in the rat pheochromocytoma (PC-12) Adh cell line. In addition, some different pharmacokinetic parameters of all compounds were in silico predicted by the QikProp module of Schrödinger’s Maestro molecular modeling package. 4-Methylsulfonylphenyl substituted compounds 3h (20%) and 4h (23%) were determined as the most promising neuroprotective agents related to their inductive roles in cell viability when compared with the 6-OHDA-positive control group (43% and 42%, respectively). Moreover, in silico pharmacokinetic results indicated that all compounds were within the acceptable range intended for human use. According to both in vitro and in silico studies, compounds 3h and 4h draw attention as potential orally bioavailable therapeutic drug candidates against neurodegeneration in PD.

Chlamydia pneumoniae (Cpn)is a gram-negative intracellular pathogen that causes a variety of pulmonary diseases, and there is growing evidence that it may play a role in Alzheimer’s disease (AD) pathogenesis. Cpn can interact functionally with host histones, altering the host’s epigenetic regulatory system by introducing bacterial products into the host tissue and inducing a persistent inflammatory response. Because Cpn is difficult to propagate, isolate, and detect, a modified LPS-like neuroinflammation model was established using lyophilized cell free supernatant (CFS) obtained from infected cell cultures, and the effects of CFS were compared to LPS. The neuroprotective effects of Trichostatin A (TSA), givinostat, and RG108, which are effective on epigenetic mechanisms, and the antibiotic rifampin, were studied in this newly introduced model and in the presence of amyloid beta (Aβ) 1–42. The neuroprotective effects of the drugs, as well as the effects of CFS and LPS, were evaluated in Aβ-induced neurotoxicity using a real-time cell analysis system, total ROS, and apoptotic impact. TSA, RG108, givinostat, and rifampin all demonstrated neuroprotective effects in both this novel model and Aβ-induced neurotoxicity. The findings are expected to provide early evidence on neuroprotective actions against Cpn-induced neuroinflammation and Aβ-induced neurotoxicity, which could represent a new treatment option for AD, for which there are currently few treatment options.

Background: Glioblastoma (GB) is an aggressive brain tumor characterized by rapid proliferation, invasion, and resistance to therapy. The substance P (SP)/neurokinin‐1 receptor (NK‐1R) pathway contributes to GB progression by promoting angiogenesis, inflammation, and extracellular matrix remodeling. Aprepitant, an FDA‐approved NK‐1R antagonist, has shown potential as a therapeutic agent in glioma treatment. Methods: This study investigates the anti‐metastatic effects of aprepitant on U87‐MG glioblastoma cells. Cell viability, migration, and invasion were evaluated using WST‐1, real‐time cell analysis, and Oris migration assays. Gene and protein expression levels were assessed by RT‐PCR, ELISA, and microarray analysis. Results: Aprepitant significantly reduced glioma cell proliferation, migration, and invasion in a dose‐dependent manner. It downregulated pro‐tumorigenic mediators such as VEGF, NF‐kB, TNF‐α, IL‐6, IL‐8, CCL3, CXCL3, and TRIM5, indicating suppression of angiogenesis, inflammation, and chemotaxis pathways. Discussion: These findings underscore the potent anti‐metastatic and anti‐angiogenic effects of NK‐1R antagonism in glioblastoma and highlight aprepitant as a promising candidate for future in vivo and in ovo therapeutic investigations targeting extracellular matrix (ECM) remodeling, chemotaxis, and angiogenesis.