title: Novel effect of paeonol on the formation of foam cells: promotion of LXRα-ABCA1-dependent cholesterol efflux in macrophages.
abstract: Paeonol, a phenolic component purified from Paeonia suffruticosa (Cortex Moutan), is used in traditional Chinese medicine to treat inflammatory diseases. However, little is known about the effect of paeonol on cholesterol metabolism. We investigated the efficacy of paeonol on cholesterol metabolism and the underlying mechanism in macrophages and apolipoprotein E deficient (apoE(-/-)) mice. Treatment with paeonol markedly attenuated cholesterol accumulation induced by oxidized LDL in macrophages, which was due to increased cholesterol efflux. Additionally, paeonol enhanced the mRNA and protein expression of ATP-binding membrane cassette transport protein A1 (ABCA1) but did not alter the protein level of ABCG1 or other scavenger receptors. Inhibition of ABCA1 activity with a pharmacological inhibitor, neutralizing antibody or small interfering RNA (siRNA), negated the effects of paeonol on cholesterol efflux and cholesterol accumulation. Furthermore, paeonol induced the nuclear translocation of liver X receptor α (LXRα) by increasing its activity. siRNA knockdown of LXRα abolished the paeonol-induced upregulation of ABCA1, promotion of cholesterol efflux and suppression of cholesterol accumulation. Moreover, atherosclerotic lesions, hyperlipidemia and systemic inflammation were reduced and the protein expression of ABCA1 was increased in aortas of paeonol-treated apoE(-/-) mice. Paeonol may alleviate the formation of foam cells by enhancing LXRα-ABCA1-dependent cholesterol efflux.
authors.affiliation: Department of Physiology, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Zhao
authors.forename: Shr-Jeng
authors.initials: SJ
authors.lastname: Jim Leu
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.forename: Kuo-Hui
authors.initials: KH
authors.lastname: Su
authors.forename: Jeng
authors.initials: J
authors.lastname: Wei
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology; D018929:Cell Culture Techniques; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005487:Foam Cells / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008517:Phytotherapy; D034741:RNA, Small Interfering; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000098:Acetophenones; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D034741:RNA, Small Interfering; C099252:oxidized low density lipoprotein; C013638:paeonol; D002784:Cholesterol