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DBZ blocks LPS-induced monocyte activation and foam cell formation via inhibiting nuclear factor-ĸB
Xinni Xie1, Shixiang Wang, Lei Xiao
1Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry and College of Life Sciences, Beijing Normal University, Beijing, P.R. China.
Background/Aims:
It has been widely accepted that chronic inflammation plays important roles in the atherogenesis. Danshensu Bingpian Zhi (DBZ) is a novel synthetic compound derived from the traditional Chinese medicine (TCM) formula Fu Fang Dan Shen (FFDS), which is effective on atherosclerosis clinically. We hypothesized that DBZ possessed the anti-atherosclerosis potentials. Here, we examined the inhibitory effects of DBZ on LPS-induced monocyte activation and foam cell formation.
Methods:
The effects of DBZ were assessed on LPS-induced inflammatory factors expression in monocyte/macrophage. Activation of NF-κB and AP-1 was analyzed by luciferase reporter assay and signaling pathway of NF-κB was investigated to elucidate mechanisms underlying DBZ mediated anti-inflammatory activity. Effects of DBZ on macrophage lipid accumulation were evaluated in native LDL and LPS co-incubated macrophages.
Results:
DBZ inhibited LPS-induced inflammatory factors expression dose dependently in monocytes. DBZ inhibited NF-κB activation strongly and AP-1 slightly. DBZ suppressed the LPS-induced degradation of IκBα, thereby decreasing the translocation of p65 to nucleus. Furthermore, DBZ suppressed LPS-activated macrophages lipid accumulation, partly due to inhibiting the expression of LPS-induced aP2 and ADRP in macrophges.
Conclusion:
These results demonstrate that DBZ has potentials on anti-atherosclerosis by suppressing monocyte activation and foam cell formation.
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