title: Purple perilla extracts with α-asarone enhance cholesterol efflux from oxidized LDL-exposed macrophages.
abstract: The cellular accumulation of cholesterol is critical in the development and progression of atherosclerosis. ATP-binding cassette (ABC) transporters play an essential role in mediating the efflux of excess cholesterol. In the current study, we investigated whether purple Perilla frutescens extracts (PPE) at a non-toxic concentration of 1-10 µg/ml stimulate the induction of the ABC transporters, ABCA1 and ABCG1, and cholesterol efflux from lipid-laden J774A.1 murine macrophages exposed to 50 ng/ml oxidized low-density lipoprotein (LDL). Purple perilla, an annual herb in the mint family and its constituents, have been reported to exhibit antioxidant and cytostatic activity, as well as to exert anti-allergic effects. Our results revealed that treatment with oxidized LDL for 24 h led to the accumulation of lipid droplets in the macrophages. PPE suppressed the oxidized LDL-induced foam cell formation by blocking the induction of scavenger receptor B1. However, PPE promoted the induction of the ABC transporters, ABCA1 and ABCG1, and subsequently accelerated cholesterol efflux from the lipid-loaded macrophages. The liver X receptor (LXR) agonist, TO-091317, and the peroxisome proliferator-activated receptor (PPAR) agonist, pioglitazone, increased ABCA1 expression and treatment with 10 µg/ml PPE further enhanced this effect. PPE did not induce LXRα and PPARγ expression per se, but enhanced their expression in the macrophages exposed to oxidized LDL. α-asarone was isolated from PPE and characterized as a major component enhancing the induction of ABCA1 and ABCG1 in macrophages exposed to oxidized LDL. α-asarone, but not β-asarone was effective in attenuating foam cell formation and enhancing cholesterol efflux, revealing an isomeric difference in their activity. The results from the present study demonstrate that PPE promotes cholesterol efflux from macrophages by activating the interaction of PPARγ-LXRα-ABC transporters.
authors: Department of Food Science and Nutrition, Hallym University, Chuncheon, Kangwon-do 200-702, Republic of Korea.
authors: Sin-Hye
authors: SH
authors: Park
authors: Department of Food Science and Nutrition, Hallym University, Chuncheon, Kangwon-do 200-702, Republic of Korea.
authors: Ji Hun
authors: JH
authors: Paek
authors: Department of Food Science and Nutrition, Hallym University, Chuncheon, Kangwon-do 200-702, Republic of Korea.
authors: Daekeun
authors: D
authors: Shin
authors: Department of Biochemistry, School of Medicine, Hallym University, Chuncheon, Kangwon-do 200-702, Republic of Korea.
authors: Jae-Yong
authors: JY
authors: Lee
authors: Department of Food Science and Nutrition, Hallym University, Chuncheon, Kangwon-do 200-702, Republic of Korea.
authors: Soon Sung
authors: SS
authors: Lim
authors: Department of Food Science and Nutrition, Hallym University, Chuncheon, Kangwon-do 200-702, Republic of Korea.
authors: Young-Hee
authors: YH
authors: Kang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D031343:Perilla / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000081248:Allylbenzene Derivatives; D000840:Anisoles; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D010936:Plant Extracts; C012195:asarone; C099252:oxidized low density lipoprotein; D002784:Cholesterol