title: Alpinetin enhances cholesterol efflux and inhibits lipid accumulation in oxidized low-density lipoprotein-loaded human macrophages.
abstract: Alpinetin is a natural flavonoid abundantly present in the ginger family. Here, we investigated the effect of alpinetin on cholesterol efflux and lipid accumulation in oxidized low-density lipoprotein (ox-LDL)-treated THP-1 macrophages and human peripheral blood monocyte-derived macrophages (HMDMs). After exposing THP-1 macrophages to alpinetin, cholesterol efflux was determined by liquid scintillator. The mRNA and protein levels of peroxisome proliferator-activated receptor gamma (PPAR-γ), liver X receptor alpha (LXR-α), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 and scavenger receptor class B member 1 were determined by reverse-transcriptase PCR (RT-PCR) and Western blot analysis, respectively. Alpinetin promoted apolipoprotein A-I- and high-density-lipoprotein-mediated cholesterol efflux and elevated PPAR-γ and LXR-α mRNA and protein expression in a dose-dependent fashion in ox-LDL-treated THP-1 macrophages and HMDMs. Small interfering RNA-mediated silencing of PPAR-γ or LXR-α dose dependently reversed alpinetin-increased cholesterol efflux in THP-1 macrophages, indicating the involvement of PPAR-γ and LXR-α in alpinetin-promoted cholesterol efflux. Alpinetin inhibited ox-LDL-induced lipid accumulation and enhanced the expression of ABCA1 and ABCG1 mRNA and protein, which was reversed by specific knockdown of PPAR-γ or LXR-α. Taken together, our results reveal that alpinetin exhibits positive effects on cholesterol efflux and inhibits ox-LDL-induced lipid accumulation, which might be through PPAR-γ/LXR-α/ABCA1/ABCG1 pathway.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Sang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D000071518:Liver X Receptors; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D057093:Orphan Nuclear Receptors / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics
chemical_list: C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D044950:Flavanones; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; C436748:alpinetin; C099252:oxidized low density lipoprotein; D002784:Cholesterol
keywords: ABCG1; ATP-binding cassette transporter A1 (ABCA1); alpinetin; cholesterol efflux; liver X receptor alpha (LXR-α); peroxisome proliferator-activated receptor gamma (PPAR-γ)