Abstract：
Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.
摘要：
动脉粥样硬化是一种以脂代谢紊乱和脂质蓄积为特征的慢性炎症性血管疾病。马西汀（EQST）是从海洋海绵来源的真菌中分离出的一种半萜化合物，具有抗菌性，抗炎,降脂，和减肥效果。尚未报道EQST是否具有抗动脉粥样硬化活性。在这项研究中,我们发现EQST通过抑制巨噬细胞炎性反应发挥抗动脉粥样硬化作用,体外脂质摄取和泡沫细胞形成，最终改善了体内高脂饮食（HFD）诱导的AopE-/-小鼠动脉粥样硬化。机械上,EQST通过在GLN247和GLN326残基上形成疏水键，以高亲和力直接结合STAT3，以及在ARG325和THR346残基的氢键。EQST与STAT3物理交互，并在功能上抑制STAT3的转录活性，从而调节动脉粥样硬化。因此,这些结果支持EQST作为开发抗动脉粥样硬化治疗剂的候选药物.
