Molecular Dereplication and In Vitro and In Silico Pharmacological Evaluation of Coriandrum sativum against Neuroblastoma Cells.

The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the "Five Rules" of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value.

Synthesis and Characterizations of a Collagen-Rich Biomembrane with Potential for Tissue-Guided Regeneration.

OBJECTIVES: In this study, a collagen-rich biomembrane obtained from porcine -intestinal submucosa for application in guided bone regeneration was developed and characterized. Then, its biological and mechanical properties were compared with that of commercial products (GenDerm [Baumer], Lumina-Coat [Critéria], Surgitime PTFE [Bionnovation], and Surgidry Dental F [Technodry]). MATERIALS AND METHODS: The biomembrane was extracted from porcine intestinal submucosa. Scanning electron microscopy, spectroscopic dispersive energy, glycosaminoglycan quantification, and confocal microscopy by intrinsic fluorescence were used to evaluate the collagen structural patterns of the biomembrane. Mechanical tensile and deformation tests were also performed. STATISTICAL ANALYSIS: The results of the methods used for experimental membrane characterizations were compared with that obtained by the commercial membranes and statistically analyzed (significance of 5%). RESULTS: The collagen-rich biomembrane developed also exhibited a more organized, less porous collagen fibril network, with the presence of glycosaminoglycans. The experimental biomembrane exhibited mechanical properties, tensile strength, and deformation behavior with improved average stress/strain when compared with other commercial membranes tested. Benefits also include a structured, flexible, and -bioresorbable characteristics scaffold. CONCLUSIONS: The experimental collagen-rich membrane developed presents physical-chemical, molecular, and mechanical characteristics similar to or better than that of the commercial products tested, possibly allowing it to actively participating in the process of bone neoformation.