Comparative study of relationship between structure of phenylethanoid glycopyranosides and their activities using cell-free assays and human cells cultured in vitro.

The study focused on protective potential of phytochemicals applicable in prevention and health protection is of great importance. Various structures of these compounds and a wide range of their biological activities have inspired organic chemists to sythesize their effective analogues in order to further increase their efficacy. The aims of our study were (i) to synthesize phenylethanoid glycopyranosides: salidroside (SALI - tyrosol ß-d-glucopyranoside), tyrosol ß-d-galactopyranoside (TYBGAL), tyrosol α-d-galactopyranoside (TYAGAL), tyrosol α-d-mannopyranoside (TYAMAN), hydroxytyrosol α-d-mannopyranoside (HOTAMA), homosyringyl ß-d-glucopyranoside (HSYGLU), hydroxytyrosol ß-d-xylopyranoside (HOTXYL) and hydroxysalidroside (HOSALI); (ii) to determine their antioxidant capacities (cell-free approaches); (iii) to evaluate their cytotoxicity (MTT test), protectivity against hydrogen peroxide (H2O2; comet assay) and effect on the intracellular glutathione level (iGSH; flow cytometry) in experimental system utilizing human hepatoma HepG2 cells. HOSALI, HOTAMA, HOTXYL and HSYGLU manifested the highest antioxidant capacity in cell-free assays and they were most active in protection of HepG2 cells against H2O2. On the other hand, pre-treatment of HepG2 cells with SALI had protective effects even though SALI displayed almost no activity in cell-free assays. Differences in the efficacy of the analogues revealed that structures of their molecules in terms of aglycone combined with sugar moiety affect their activities.

Salidroside, a Chemopreventive Glycoside, Diminishes Cytotoxic Effect of Cisplatin in Vitro.

Natural products represent the source or the inspiration for the majority of the active ingredients of medicines because of their structural diversity and a wide range of biological effects. Our aims in this study were (i) to synthesize enzymatically salidroside (SAL), the most effective phenylethanoid glycoside in Rhodiola species; (ii) to examine its antioxidant capacity using cell-free assays (reducing power, DPPH radicals scavenging and Fe2+ -chelating assays); (iii) to assess its DNA-protective potential on plasmid DNA (DNA topology assay) and in HepG2 cells (comet assay) damaged by Fe2+ ions and hydrogen peroxide, respectively; and (iv) to investigate the effects of SAL, cisplatin (CDDP) and combined treatments of SAL + CDDP on cell viability (MTT test), level of DNA damage (comet assay), proliferation, cell cycle (flow cytometry) and the expression of signalling molecules associated with cell growth and apoptotic pathways (Western immunoblotting). We found out that SAL manifested low antioxidant and DNA-protective capacity in all assays used. In both parental A2780 and CDDP-resistant A2780/CP human ovarian carcinoma cells, SAL itself exerted in fact no impact on the viability, while in combination with CDDP it showed antagonistic effect supporting the chemopreventive activity on the CDDP-induced cell damage. These results were confirmed by the partial reversal of the cell cycle alterations and the DNA damage level, as well as with partial restoration of cell survival/signalling pathways, when the expression of these molecules partially returned to their proper levels.