title: Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP-1-derived macrophages.
abstract: Increased macrophage cholesterol efflux (ChE) is considered to have anti-atherosclerotic effect counteracting cardiovascular disease. The principle pungent ingredient of the fruits of Piper nigrum, piperine, is identified in this study as a ChE inducer in THP-1-derived macrophages, and mechanisms underlying this effect are explored.
  
  
  
  Without affecting cell viability, piperine concentration-dependently enhances ChE in THP-1-derived macrophages from 25 to 100 μM. The expression level of the key cholesterol transporter protein ATP-binding cassette transporter A1 (ABCA1) is significantly upregulated by piperine, as revealed by western blot analyses. However, two other ChE-mediating transporter proteins, ATP-binding cassette transporter G1 (ABCG1) and scavenger receptor class B member 1 (SR-B1), remain unaffected. Piperine exerts no influence on ABCA1 mRNA levels, but significantly inhibits the degradation of ABCA1, as evident by an increased half-life of the protein in the presence of cycloheximide. Furthermore, it is found that piperine likely interferes with the calpain-mediated ABCA1 degradation pathway and exhibits significant inhibition of calpain activity.
  
  
  
  Our findings suggest that piperine promotes ChE in THP-1-derived macrophages by upregulation of ABCA1, which might be mediated by inhibition of calpain activity. This novel bioactivity makes the dietary constituent piperine a good candidate to be further explored for therapeutic or preventive applications in the context of atherosclerosis.
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Palme
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rotter
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schilcher
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Malsor
authors.initials: M
authors.lastname: Cukaj
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Ladurner
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Elke H
authors.initials: EH
authors.lastname: Heiss
authors.affiliation: Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Stangl
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.|Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.
authors.forename: Atanas G
authors.initials: AG
authors.lastname: Atanasov
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000187:drug effects* / Q000378:metabolism; D000465:Algorithms; D000470:Alkaloids / Q000494:pharmacology*; D050197:Atherosclerosis / Q000378:metabolism; D052117:Benzodioxoles / Q000494:pharmacology*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D029222:Piper nigrum / Q000737:chemistry; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018528:ATP-Binding Cassette Transporters; D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; C008922:piperine
keywords: ABCA1; Calpain; Cholesterol efflux; Macrophages; Piperine