Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages.
Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.
Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. Electronic address: Kazuaki_Ohara@kirin.co.jp.
Kazuaki
K
Ohara
Hideyuki
H
Wakabayashi
Yoshimasa
Y
Taniguchi
Kazutoshi
K
Shindo
Hiroaki
H
Yajima
Aruto
A
Yoshida
D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000517:prevention & control; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D005419:Flavonoids / Q000032:analysis / Q000494:pharmacology; D008024:Ligands; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D031653:Nelumbo / Q000737:chemistry; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D064286:ATP Binding Cassette Transporter 1; D000924:Anticholesteremic Agents; D002784:Cholesterol; D005419:Flavonoids; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010936:Plant Extracts; D011794:Quercetin; C577833:Abca1 protein, mouse; C000605214:Nr1h3 protein, mouse; C443401:quercetin 3-O-glucuronide
ABCA1; ATP-binding cassette, subfamily A, member 1; HDL; HDLC; LXRα; Macrophage; NNE; Nelumbo nucifera; Nelumbo nucifera leaf extracts; Q3GA; Quercetin-3-O-glucuronide; RCT; high density lipoprotein; high density lipoprotein-cholesterol; liver X receptor alpha; quercetin-3-O-glucuronide; reverse cholesterol transport