Anti-inflammatory, anti-osteoclastogenic and antioxidant effects of malva sylvestris extract and fractions: In vitro and in vivo studies

Abstract

Dynamics of adsorbate-islands' formation at condensation from gaseous phase is studied in the framework of the generalized approach based on reaction- diffusion models. As found, the stabilization of nanopatterns in suchclass models is achieved by nonequilibrium chemical reactions responsible for formation of complexes. It is found that, during the system evolution, pattern- selection processes are realized. As shown, the possible oscillatory regimes for islands' formation are realized at finite propagation speed related to nonzero relaxation time for the diffusion flux. An influence of internal multiplicative noise on the pattern-formation processes is studied. As shown, such noise at small intensities governs transitions between ordered thermodynamical dense and diluted phases. These phase transitions are characterized by an increase of fluctuations of the coverage field and correlation radius of spatial modulations. An influence of local change in surface temperature due to adsorption-desorption processes on the adsorbate-islands' formation processes at condensation from gaseous phase is studied. As found, the thermal effects shrink the range of temperature and pressure, when pattern formation is possible. As shown considering statistical properties of surface structures, the transitions between ordered phases related to low-And high-density states are accompanied by a formation of adsorbate or vacancy islands. It is found that spherical adsorbate and vacancy islands are characterized by different distribution functions over their sizes for different symmetries of substrate lattices. As shown, depending on system control parameters, island size distributions can change their modality. The size of localized adsorbate/vacancy clusters can be characterized by nanometre scale, and the size of these islands can be controlled by both primary and secondary mechanisms of pattern formation. A generalized model for adsorbateislands' formation in multilayer systems is proposed by taking into account transference reactions between layers. As shown, in such a system, a cascade of first-order phase transitions is realized. The number of such phase transitions is defined through the number of layers., Given their medical importance, natural products represent a tremendous source of drug discovery. The aimof this study was to investigate Malva sylvestris L. extract and fractions and their pharmacological activities followed by chemical identification. The aqueous fraction (AF) was identified as the bioactive fraction in the in vitro and in vivo assays. The AF controlled the neutrophil migration to the peritoneal cavity by 66%, inhibited the antiedematogenic activity by 58.8%, and controlled IL-1β cytokine expression by 54%. The in vitro viability tests showed a concentration-dependent effect, where the MSE and fractions at concentrations under 10 μg/ mL were non-Toxic to cells. Transcriptional factors of carbonic anhydrase II (CAII), cathepsin K (Ctsk) and tartrate-resistant acid phosphatase (TRAP) were analyzed by qPCR in RAW264.7 cell lines. The gene expression analysis showed that the AF was the only treatment that could downregulate all the study genes: CAII, Ctsk and TRAP (p<0.05). TRAP staining was used to evaluate osteoclast formation. AF treatments reduced the number of osteoclastogenesis 2.6- fold compared to the vehicle control group.Matrixmetalloproteinase 9 (MMP-9) activity decreased 75% with the AF treatment. Moreover, the bioactive fraction had the ability to regulate the oxidation pathway in the ABTS (2,2-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) assay with an activity equivalent to 1.30 μmol Trolox/g and DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals 1.01 g/L. Positive ion ESI-mass spectrometry for molecular ions at m/z 611 and 633 confirmed rutin as the major compound in the AF. The AF ofM. sylvestris presented antiinflammatory, controlled osteoclastogenic mechanisms and antioxidant abilities in different in vitro and in vivo methods. In addition, we suggest that given its multi-Target activity the bioactive fraction may be a good candidate in the therapy of chronic inflammatory diseases.