[Polydatin inhibits cell proliferation and expressions of inflammatory cytokines in THP-1 cells induced by ox-LDL via up-regulating SIRT1].

Objective To investigate the effects of polydatin on cell proliferation and cytokine expression in THP-1 monocyte-derived macrophages (MDMs) induced by oxidized low-density lipoprotein (ox-LDL), and the possible mechanisms. Methods MDMs were divided into the control group (only treated with ordinary culture medium), ox-LDL group (treated wtih 80 μmol/L ox-LDL for 24 hours), polydatin treatment group (treated with 100 μmol/L polydatin for 2 hours prior to the treatment with 80 μmol/L ox-LDL for 24 hours) and EX-527 treatment group (treated with 10 μmol/L SIRT1 inhibitor EX-527 for 2 hours prior to the treatment with ox-LDL and polydatin). The effects of polydatin on ox-LDL-induced oxidative proliferation and cytokine expression in MDMs were evaluated by CCK-8 assay. Spectrofluorometry was used to determine the intracellular level of superoxide dismutase (SOD) and malondialdehyde (MDA). DCFH-DA loading was used to detect the content of reactive oxidative species (ROS). The levels of silent mating type information regulator 1 (SIRT1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were examined by real-time quantitative PCR and Western blotting. Results Polydatin (100 μmol/L) inhibited the proliferation of MDMs induced by ox-LDL, decreased the levels of MDA and ROS, whereas the level of SOD increased. The mRNA and protein levels of SIRT1 in MDMs were inhibited by ox-LDL, whereas the expressions of MCP-1, TNF-α and IL-6 were promoted. Pre-treatment with EX-527 attenuated the inhibitory effects of polydatin on the proliferation of MDMs, inhibited the expressions of SIRT1, promoted the expressions of MCP-1, TNF-α and IL-6. Conclusion Polydatin up-regulates the expression of SIRT1 to increase the ability of anti-macrophage proliferation, reduce the level of the intracellular ROS induced by ox-LDL, and inhibit the expression of inflammatory cytokines.