PMID- 22922992 OWN - NLM STAT- MEDLINE DCOM- 20130307 LR - 20211203 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 30 IP - 5 DP - 2012 Nov TI - Sage weed (Salvia plebeia) extract antagonizes foam cell formation and promotes cholesterol efflux in murine macrophages. PG - 1105-12 LID - 10.3892/ijmm.2012.1103 [doi] AB - 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 microg/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 microg/ml SWE most likely through the induction of ABCA1 and ABCG1 and the secretion of apoE. Although 10 microM 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. FAU - Park, Sin-Hye AU - Park SH AD - Department of Food and Nutrition, Hallym University, Chuncheon 200-702, Republic of Korea. FAU - Kim, Jung-Lye AU - Kim JL FAU - Kang, Min-Kyung AU - Kang MK FAU - Gong, Ju-Hyun AU - Gong JH FAU - Han, Seon-Young AU - Han SY FAU - Shim, Jae-Hoon AU - Shim JH FAU - Lim, Soon Sung AU - Lim SS FAU - Kang, Young-Hee AU - Kang YH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120820 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (6-methoxy-4',5-dihydroxyflavone-7-O-glucoside) RN - 0 (ABCA1 protein, human) RN - 0 (ABCG1 protein, mouse) RN - 0 (ATP Binding Cassette Transporter 1) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Apolipoproteins E) RN - 0 (Camphanes) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Flavones) RN - 0 (Flavonoids) RN - 0 (Glucosides) RN - 0 (Lipoproteins) RN - 0 (Lipoproteins, LDL) RN - 0 (Scarb1 protein, mouse) RN - 0 (Scavenger Receptors, Class B) RN - 0 (danshen dripping pill) RN - 0 (oxidized low density lipoprotein) RN - 97C5T2UQ7J (Cholesterol) RN - N7F61604C2 (hispidulin) SB - IM MH - ATP Binding Cassette Transporter 1 MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/genetics/metabolism MH - Animals MH - Apolipoproteins E/metabolism MH - Camphanes MH - Cell Line MH - Cholesterol/*metabolism MH - Drugs, Chinese Herbal/*pharmacology MH - Flavones/pharmacology MH - Flavonoids/pharmacology MH - Foam Cells/*drug effects MH - Gene Expression/drug effects MH - Glucosides/pharmacology MH - Humans MH - Lipoproteins/genetics/metabolism MH - Lipoproteins, LDL/metabolism/physiology MH - Macrophages/drug effects/metabolism MH - Mice MH - Panax notoginseng MH - Salvia/*chemistry MH - Salvia miltiorrhiza MH - Scavenger Receptors, Class B/genetics/metabolism MH - Transcriptional Activation/drug effects EDAT- 2012/08/28 06:00 MHDA- 2013/03/08 06:00 CRDT- 2012/08/28 06:00 PHST- 2012/05/21 00:00 [received] PHST- 2012/07/27 00:00 [accepted] PHST- 2012/08/28 06:00 [entrez] PHST- 2012/08/28 06:00 [pubmed] PHST- 2013/03/08 06:00 [medline] AID - 10.3892/ijmm.2012.1103 [doi] PST - ppublish SO - Int J Mol Med. 2012 Nov;30(5):1105-12. doi: 10.3892/ijmm.2012.1103. Epub 2012 Aug 20.