摘要：

BACKGROUND AND PURPOSE: Cryptotanshinone (CTS) is a major bioactive diterpenoid isolated from Danshen, an eminent medicinal herb that treats cardiovascular disorders in Asian medicine.However, it remains unknown whether CTS can prevent experimental atherosclerosis.The present study was designed to investigate the protective effects and whereby the molecular mechanisms of CTS on atherosclerosis.EXPERIMENTAL APPROACH: Apolipoprotein E deficient (ApoE-/-) mice fed an atherogenic diet were dosed daily with CTS (15, 45 mg/kg/d) by oral gavage.In vitro studies were carried out in oxidized LDL (oxLDL)-stimulated human umbilical vein endothelial cells (HUVECs) treated with or without CTS.KEY RESULTS: CTS significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in ApoE-/-mice by inhibiting lectin-like oxLDL receptor-1 (LOX-1) and matrix metalloproteinase-9 (MMP-9) expression, as well as inhibiting reactive oxygen species (ROS) generation and nuclear factor-kappa B (NF-κB) activation.CTS treatment led to a significant decrease in serum pro-inflammatory mediators, without altering serum lipid profile.In vitro, CTS decreased oxLDL-induced LOX-1 mRNA and protein expression, and thereby, inhibited LOX-l-mediated monocytes adhesion to HUVECs through reducing the expression of adhesion molecules (ICAM-1 and VCAM-1).Furthermore, we observed that, CTS inhibited NADPH oxidase subunit 4 (NOX4)-mediated ROS generation and consequent activation of NF-κB in HUVECs.CONCLUSIONS AND IMPLICATIONS: The present findings unveil the novel anti-atherosclerotic activity of CTS through the inhibition of LOX-1 mediated signaling pathway and suggest that CTS is a vasculoprotective drug that has potential therapeutic value in clinical treatment of atherosclerotic cardiovascular diseases.

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