Li Zhi-Qiang, Huang Xiu-Ying, Hu Chun-Yan, Zhu Zhong-Sheng, Chen Yang, Gong Min
Pharmazie. 2019 Oct 1;74(10):601-605. doi: 10.1691/ph.2019.9506.
Atherosclerosis (AS) is characterized by the significant accumulation of low-density lipoprotein (LDL)-cholesterol in macrophages that reside in the vessel wall and the resultant inflammatory response. Therefore, inhibition of LDL-induced inflammation is a promising interference for AS. Many traditional Chinese medicine prescriptions have been developed for AS treatment. Geniposide (GEN) is an iridoid glycoside mainly found in fruit. Although GEN has previously been shown to possess anti-atherosclerotic activities, its effects on the formation of macrophage-derived foam cells remain poorly characterized. In our current study, we demonstrated that GEN could significantly inhibit oxidized light-density lipoprotein (ox-LDL) induced macrophage foam cell formation and the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, treatment of GEN in bone-marrow derived macrophages repressed iNOS expression and NO expression. GEN could also alleviate ox-LDL-dependent up-regulation of CD36 expression by blocking the phosphorylation of p38 MAPK, ERK, JNK and NF-kB p65. The results of our current study demonstrate that GEN exhibits significant therapeutic effects against ox-LDA-induced foam cell formation and inflammation. Therefore, GEN is promising agent for treating AS.
动脉粥样硬化（AS）的特征是低密度脂蛋白（LDL）胆固醇在血管壁内的巨噬细胞中大量积聚，并引发炎症反应。因此，抑制LDL诱导的炎症是一种有前景的AS干预措施。已经开发了许多中药方剂用于治疗AS。栀子苷（GEN）是一种主要存在于果实中的环烯醚萜苷。尽管GEN先前已被证明具有抗动脉粥样硬化活性，但其对巨噬细胞源性泡沫细胞形成的影响仍不清楚。在我们目前的研究中，我们证明GEN可以显著抑制氧化型低密度脂蛋白（ox-LDL）诱导的巨噬细胞泡沫细胞形成以及促炎细胞因子的表达，且呈剂量依赖性。此外，在骨髓来源的巨噬细胞中用GEN处理可抑制诱导型一氧化氮合酶（iNOS）表达和一氧化氮（NO）表达。GEN还可以通过阻断p38丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和核因子κB p65（NF-kB p65）的磷酸化来减轻ox-LDL依赖性的CD36表达上调。我们目前的研究结果表明，GEN对ox-LDA诱导的泡沫细胞形成和炎症具有显著的治疗作用。因此，GEN是一种有前景的治疗AS的药物。
