三七总皂苷对炎症诱导的内皮黏附分子表达和单核细胞黏附的抑制作用的比较研究。
Comparative study on saponin fractions from Panax notoginseng inhibiting inflammation-induced endothelial adhesion molecule expression and monocyte adhesion.
机构信息
State Key Laboratory of Quality Research in Chinese Medicine (University of Macau), Macao SAR, China.
出版信息
Chin Med. 2011 Oct 13;6:37. doi: 10.1186/1749-8546-6-37.
BACKGROUND
Panax notoginseng is commonly used for the treatment of cardiovascular diseases in China. The present study investigates the effects of three different saponin fractions (ie total saponins, PNS; protopanaxadiol-type saponin, PDS; and protopanaxatriol-type saponin, PTS) and two major individual ingredients (ie ginsenoside Rg1 and Rb1) from P. notoginseng on the endothelial inflammatory response in vitro and in vivo.
METHODS
Recombinant human tumor necrosis factor-α (TNF-α) was added to the culture medium of human coronary artery endothelial cells (HCAECs) to induce an inflammatory response. A cell adhesion assay was used to determine the effect of the P. notoginseng saponin fractions on endothelial-monocyte interaction. The cell adhesion molecule (CAMs) expression, including ICAM-1 and VCAM-1, in the protein level on the surface of endothelial cells were measured by cellular ELISA. CAMs expression in mRNA level was also assayed by qRT-PCR in the HCAECs and the aorta of rat fed with high cholesterol diet (HCD). Western blotting was used to detect effect of the saponin fractions on CAMs protein expression in HCAECs. In addition, nuclear translocation of p65, a surrogate marker for NF-κB activation, was measured by immunostaining.
RESULTS
Three saponin fractions and two individual ginsenosides exhibited the inhibitory effects on monocyte adhesion on TNF-α-activated HCAECs and expression of ICAM-1 and VCAM-1 at both mRNA and protein levels in vitro. The saponin fractions exhibited a similar trend of the inhibitory effects on the mRNA expression of CAMs in the aorta of HCD-fed rat in vivo. These inhibitory effect of saponin fractions maybe attribute partially to the suppression of the TNF-α-induced NF-κB activation.
CONCLUSION
Our data demonstrate that saponin fractions (ie PNS, PDS and PTS) and major individual ginsenosides (ie Rg1 and Rb1) have potential anti-atherogenic effects. Among the tested saponin fractions, PDS is the most potent saponin fraction against TNF-α-induced monocyte adhesion as well as the expression of adhesion molecules in vitro and in vivo.
背景
三七常用于治疗中国的心血管疾病。本研究调查了三种不同皂苷（即总皂苷、PNS；原人参二醇型皂苷、PDS；和原人参三醇型皂苷、PTS）和两种主要单体成分（即人参皂苷 Rg1 和 Rb1）对体外和体内内皮炎症反应的影响。
方法
在人冠状动脉内皮细胞（HCAEC）的培养基中加入重组人肿瘤坏死因子-α（TNF-α）诱导炎症反应。通过细胞黏附试验测定三七皂苷对内皮细胞-单核细胞相互作用的影响。用细胞 ELISA 法测定内皮细胞表面细胞黏附分子（CAM）的表达，包括 ICAM-1 和 VCAM-1。用 qRT-PCR 法测定 HCAEC 和高胆固醇饮食（HCD）喂养大鼠主动脉中 CAM 的 mRNA 水平。用 Western blotting 法检测皂苷对 HCAEC 中 CAM 蛋白表达的影响。此外，通过免疫染色法检测 NF-κB 激活的替代标志物 p65 的核转位。
结果
三种皂苷和两种单体人参皂苷在体外均抑制 TNF-α激活的 HCAEC 上单核细胞黏附和 ICAM-1 和 VCAM-1 的 mRNA 和蛋白水平表达。皂苷在体内也表现出抑制 HCD 喂养大鼠主动脉中 CAM mRNA 表达的相似趋势。皂苷的这种抑制作用可能部分归因于对 TNF-α诱导的 NF-κB 激活的抑制。
结论
我们的数据表明，皂苷（即 PNS、PDS 和 PTS）和主要单体人参皂苷（即 Rg1 和 Rb1）具有潜在的抗动脉粥样硬化作用。在测试的皂苷中，PDS 是最有效的皂苷，可抑制 TNF-α诱导的单核细胞黏附和体外及体内黏附分子的表达。
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