Biology subjects

Boldizsar, I.

Publications and source records attributed to Boldizsar, I..

3 recordsLinked to original sources

bioRxiv2025

Petasol Exhibits Rapid and Efficient Epithelial Transport in Epithelial Barrier Models

The epithelial permeability of petasol, a sesquiterpene derivative with reported antiviral properties, remains largely unexplored despite its potential as a therapeutic candidate. Here, we systematically characterize the transport of petasol across epithelial barriers using a combination of in vitro transwell models, automated millifluidic sampling, mathematical modeling, optical- and HPLC-mass spectroscopy. Vero E6 and Caco-2 cell layers were employed as epithelial barrier models, with transepithelial electrical resistance (TEER) measurements confirming the formation of functionally intact epithelial layers. Mathematical modeling of passive diffusion and cellular uptake allowed estimation of key transport parameters, including permeability coefficients and intracellular sequestration rates. Trans-barrier transport of petasol was compared to that of nitazoxanide, chloroquine, and FITC-dextran. Our results reveal that petasol exhibits efficient and rapid transport across both epithelial cell types without substantial intracellular accumulation or metabolic degradation, suggesting favorable properties for systemic delivery.

pharmacology and toxicology↗

bioRxiv2025

Characterizing Solute Transport Across Cell Layers: Artifact Correction and Parameter Extraction from a Simplified Three-Compartment Model

Quantifying solute transport across epithelial cell layers grown on transwell inserts is a common approach in early-stage drug development to estimate pharmacokinetic properties such as absorption and bioavailability. To increase throughput and reduce variability, these assays are increasingly automated, including the use of robotic or microfluidic systems for time-resolved sampling. However, both automated and manual sampling can introduce systematic artifacts, such as residual volume retention and surface adsorption, that distort concentration time series and affect downstream analysis. To fully realize the potential precision of automated measurements, we propose a mathematical correction to account for sampling artifacts; then to fit the corrected data to a three-compartment model that captures membrane diffusion, cellular sequestration, and metabolic loss. The method is demonstrated on datasets from transwell epithelial barrier transport assays. We suggest that the considered three-compartment model yields mechanistically more meaningful parameters than the conventional apparent permeability (Papp) measure. The proposed approach thus enables more accurate characterization of analyte interactions with the barrier cell layer, supporting better-informed assessments of compound behavior in in vitro transport systems.

pharmacology and toxicology↗

bioRxiv2022

Anti-glutamatergic effects of three lignan compounds: arctigenin, matairesinol and trachelogenin - An ex vivo study on rat brain slices

Arctigenin is a bioactive dibenzylbutyrolactone-type lignan exhibiting various pharmacological activities. The neuroprotective effects of arctigenin were demonstrated to be mediated via inhibition of AMPA/KA type glutamate receptors in the somatosensory cortex of the rat brain. The aim of this study was to compare the effects of arctigenin with matairesinol and trachelogenin on synaptic activity in ex vivo rat brain slices. Arctigenin, matairesinol and trachelogenin were isolated from Arctium lappa, Centaurea scabiosa and Cirsium arvense, respectively, and applied on brain slices via perfusion medium at the concentration range of 0.5-40 M. The effects of the lignans were examined in the CA1 hippocampus and the somatosensory cortex by recording electrically evoked field potentials. Arctigenin and trachelogenin caused a significant dose-dependent decrease in the amplitude of hippocampal population spikes (POPS) and the slope of excitatory postsynaptic potentials (EPSPs), whereas matairesinol (1 M and 10 M) decreased EPSP slope but had no effect on POPS amplitude. Trachelogenin effect (0.5 M, 10 M, 20 M) was comparable to arctigenin (1 M, 20 M, 40 M) (p > 0.05). In the neocortex, arctigenin (10 M, 20 M) and trachelogenin (10 M) significantly decreased the amplitude of evoked potential early component, while matairesinol (1 M and 10 M) had no significant effect (p>0.05). The results suggest that trachelogenin and arctigenin act via inhibition of AMPA/KA receptors in the brain and trachelogenin has a higher potency than arctigenin. Thus, trachelogenin and arctigenin could serve as lead compounds in the development of alternative neuroprotective drugs.

pharmacology and toxicology↗