Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Third Military Medical University, Chongqing 400038, China.
J Ethnopharmacol. 2012 Aug 1;142(3):732-8. doi: 10.1016/j.jep.2012.05.053. Epub 2012 Jun 7.
Panax notoginseng (Burk.) F.H. Chen has been used as a health product and natural remedy in traditional medicine for cardiovascular diseases for more than 1000 years in Asia, including China, Japan, and Korea. Panax notoginseng saponins (PNS) are the major effective ingredients extracted from Panax notoginseng.
The purpose of this study was to investigate whether Panax notoginseng saponins (PNS) attenuated atherosclerosis by inducing liver X receptor alpha (LXRα) expression and to elucidate the mechanisms responsible for the effects.
The AS rats were treated once daily with PNS (100 mg/kg, i.p.), and pathological changes in the aorta were observed using Sudan IV staining. The expression of LXRα in the aortic wall was measured by Western blot analysis. THP-1 macrophages were cultured with PNS in the presence or absence of geranylgeranyl pyrophosphate ammonium salt (GGPP), an LXRα antagonist. The expression of LXRα and its target genes ATP-binding cassette A1 and G1 (ABCA1, ABCG1) were determined by qRT-PCR. The transcriptional activation of the LXRα gene promoter was analyzed by a reporter assay. The NF-κB DNA binding activity and the expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1) was evaluated respectively by Trans-AM NF-κB ELISA and ELISA in THP-1 macrophages that were stimulated with LPS after treatment with PNS and GGPP.
PNS treatment alleviated the typical pathological changes associated with atherosclerosis in rats. The expression of LXRα was increased in rat aortas after treatment with PNS. In vitro, PNS increased LXRα mRNA levels in THP-1 macrophages. The reporter assays showed that PNS enhanced transcriptional activation of the LXRα gene promoter and led to the upregulation of ABCA1 and ABCG1 expression. This upregulation could be reversed by treatment with GGPP. Additionally, PNS inhibited NF-κB DNA binding activity and reduced secretion of IL-6 and MCP-1 in LPS-stimulated THP-1 macrophages. These effects could be reversed by GGPP.
The results indicated that the PNS-mediated attenuation of AS may, at least partly, due to LXRα uprergulation. The mechanisms of action included enhancement transcriptional activation of the LXRα gene promoter by PNS and subsequent upregulation of ABCA1 and ABCG1 and inhibition of NF-κB DNA binding activity.
三七（Burk.）F.H. Chen 作为一种保健品和天然药物，在包括中国、日本和韩国在内的亚洲传统医学中，已有 1000 多年的心血管疾病治疗历史。三七总皂苷（PNS）是从三七中提取的主要有效成分。
本研究旨在探讨三七总皂苷（PNS）是否通过诱导肝 X 受体α（LXRα）表达来减轻动脉粥样硬化，并阐明其作用机制。
采用苏丹 IV 染色观察 AS 大鼠主动脉的病理变化，用 PNS（100mg/kg，腹腔注射）治疗 AS 大鼠，每日一次。通过 Western blot 分析测量主动脉壁中 LXRα的表达。在存在或不存在香叶基香叶基焦磷酸铵（GGPP）的情况下，用 PNS 培养 THP-1 巨噬细胞，GGPP 是 LXRα的拮抗剂。通过 qRT-PCR 测定 LXRα及其靶基因 ATP 结合盒转运蛋白 A1 和 G1（ABCA1、ABCG1）的表达。通过报告基因分析检测 LXRα基因启动子的转录激活。用 Trans-AM NF-κB ELISA 和 ELISA 分别评估 LPS 刺激后用 PNS 和 GGPP 处理的 THP-1 巨噬细胞中 NF-κB DNA 结合活性和白细胞介素（IL）-6、单核细胞趋化蛋白-1（MCP-1）的表达。
PNS 治疗可减轻大鼠动脉粥样硬化的典型病理变化。用 PNS 治疗后，大鼠主动脉中 LXRα的表达增加。体外，PNS 增加了 THP-1 巨噬细胞中 LXRα mRNA 水平。报告基因检测显示，PNS 增强了 LXRα基因启动子的转录激活，导致 ABCA1 和 ABCG1 表达上调。用 GGPP 处理可逆转这种上调。此外，PNS 抑制 LPS 刺激的 THP-1 巨噬细胞中 NF-κB DNA 结合活性和 IL-6、MCP-1 的分泌。用 GGPP 处理可逆转这些作用。
结果表明，PNS 介导的 AS 减弱可能至少部分归因于 LXRα的上调。作用机制包括 PNS 增强 LXRα基因启动子的转录激活，随后上调 ABCA1 和 ABCG1，并抑制 NF-κB DNA 结合活性。
