目的 从反柄紫芝Ganoderma cochlear中寻找具有抗动脉粥样硬化潜力的活性分子。方法 采用硅胶柱色谱、反相C₁₈柱色谱及半制备高效液相色谱等技术进行分离纯化，并通过多种谱学技术（1D、2D NMR）鉴定化合物结构；采用氧化低密度脂蛋白（oxidized low-density lipoprotein，ox-LDL）诱导的巨噬细胞脂质沉积模型评估化合物体外抗动脉粥样硬化潜力，通过Western blotting技术检测相关表型蛋白的变化。结果 从反柄紫芝中分离鉴定了1个新的杂萜化合物2′,5′-二羟基-6-(2-羟基丙-2-基)-[1,1′-联苯]-3-羧酸甲酯，命名为反柄紫芝杂萜A（1）。BODIPY和油红O染色结果表明，化合物1能够显著抑制ox-LDL诱导的巨噬细胞脂质沉积，降低三酰甘油（triglycerides，TG）、降低总胆固醇（total cholesterol，TC）水平，且具有剂量相关性。同时，Western blotting结果表明化合物1能够下调白细胞分化抗原36（cluster of differentiation 36，CD36）和清道夫受体A（class A scavenger receptor，SR-A）的表达、同时上调ATP结合盒转运体A1（ATP-binding cassette transporter A1，ABCA1）的表达。结论 从反柄紫芝中分离了1个结构新颖的杂萜化合物，且化合物1具有显著的抗动脉粥样硬化潜力。

Objective To discover anti-atherosclerotic compounds from Ganoderma cochlear. Methods Silica gel column chromatography, reversed-phase C₁₈ column chromatography, and semi-preparative HPLC were used for isolation and purification, and the structures of the isolates were elucidated by various spectroscopic techniques (1D and 2D NMR). The in vitro anti-atherosclerotic activity of compound was evaluated using an ox-LDL-induced macrophage lipid deposition model, and the expression of phenotype-related protein was detected by Western blotting. Results A previously undescribed meroterpenoid, designated as cochlemeroid A (1), was isolated and identified from G. cochlear. BODIPY and Oil Red O staining showed that compound 1 significantly inhibited ox-LDL-induced macrophage lipid deposition in a dose-dependent manner, accompanied by reduced TC and TG levels. Furthermore, Western blotting results demonstrated that compound 1 downregulated the expression of cluster of differentiation 36 (CD36) and class A scavenger receptor (SR-A), while upregulating the expression of the ATP-binding cassette transporter A1 (ABCA1). Conclusion In this study, a new meroterpenoid was successfully isolated from G. cochlear. The bioactivity results indicated that compound 1 possessed significant antiatherosclerotic potential.

R284.1

国家自然科学基金项目（82204226）