Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Republic of Korea.
Int J Mol Med. 2012 Nov;30(5):1105-12. doi: 10.3892/ijmm.2012.1103. Epub 2012 Aug 20.
Lipid-laden peripheral tissue cells release cholesterol to an extracellular acceptor such as high-density lipoprotein (HDL). Foam cells are formed at the first stage of atherosclerosis development. This study investigated whether sage weed (Salvia plebeia) extract (SWE) influences cholesterol handling of J774A1 murine macrophages. A murine macrophage cell line, J774A1, was used in this study. Oxidized low-density lipoproteins (LDL) treatment was used for foam cell formation, which was confirmed using Oil red O staining. The oxidized LDL uptake and cholesterol efflux from lipid-laden foam cell-associated proteins were detected by western blot analysis. Also, transcriptional levels of these associated genes were examined using reverse transcription-PCR. Also, cholesterol efflux was measured using NBD-cholesterol efflux assay. Non-toxic SWE at ≥10 µg/ml attenuated scavenger receptor (SR)-B1 expression of macrophages induced by oxidized LDL for 6 h, which was achieved at its transcriptional levels. Consistently, SWE suppressed oxidized LDL-stimulated cellular lipid accumulation and foam cell formation due to downregulated SR-B1. SWE upregulated the protein expression and mRNA levels of ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) in lipid-laden foam cells, both responsible for cholesterol efflux. In addition, SWE promoted apolipoprotein E (apoE) secretion from oxidized LDL-induced foam cells. Cholesterol efflux was enhanced by ≥10 µg/ml SWE most likely through the induction of ABCA1 and ABCG1 and the secretion of apoE. Although 10 µM homoplantaginin, a compound mainly present in sage weeds, did not influence cellular expression of ABCA1 and ABCG1, it suppressed oxidized LDL-enhanced SR-B1 induction and foam cell formation. These results demonstrate that SWE antagonized oxidized LDL uptake and promoted cholesterol efflux in lipid-laden macrophages. Therefore, SWE may serve as a protective therapeutic agent against the development of atherosclerosis.
富含脂质的外周组织细胞将胆固醇释放到细胞外接受体，如高密度脂蛋白（HDL）。泡沫细胞是动脉粥样硬化发展的第一阶段形成的。本研究探讨了鼠李草（Salvia plebeia）提取物（SWE）是否影响 J774A1 鼠巨噬细胞的胆固醇处理。本研究使用了鼠巨噬细胞系 J774A1。用氧化型低密度脂蛋白（LDL）处理诱导泡沫细胞形成，并用油红 O 染色证实。通过 Western blot 分析检测脂质负载泡沫细胞相关蛋白的氧化型 LDL 摄取和胆固醇流出。还使用逆转录-PCR 检查这些相关基因的转录水平。还使用 NBD-胆固醇流出测定法测量胆固醇流出。≥10µg/ml 的无毒 SWE 可减轻氧化型 LDL 诱导的巨噬细胞在 6 小时内的清道夫受体（SR）-B1 表达，这是在其转录水平上实现的。一致地，SWE 抑制了由于 SR-B1 下调而导致的氧化型 LDL 刺激的细胞脂质积累和泡沫细胞形成。SWE 上调了载脂蛋白 E（apoE）在脂质负载泡沫细胞中的蛋白表达和 mRNA 水平，两者均负责胆固醇流出。此外，SWE 促进了载脂蛋白 E（apoE）从氧化型 LDL 诱导的泡沫细胞中的分泌。≥10µg/ml 的 SWE 增强了胆固醇流出，这很可能是通过诱导 ABCA1 和 ABCG1 以及 apoE 的分泌。虽然 10µM 同源 Plantaginin，一种主要存在于鼠李草中的化合物，不会影响 ABCA1 和 ABCG1 的细胞表达，但它抑制了氧化型 LDL 增强的 SR-B1 诱导和泡沫细胞形成。这些结果表明，SWE 拮抗了氧化型 LDL 的摄取并促进了富含脂质的巨噬细胞中的胆固醇流出。因此，SWE 可能是预防动脉粥样硬化发展的保护性治疗剂。
