PMID- 27862930
OWN - NLM
STAT- MEDLINE
DCOM- 20171113
LR  - 20230120
IS  - 1613-4133 (Electronic)
IS  - 1613-4125 (Print)
IS  - 1613-4125 (Linking)
VI  - 61
IP  - 4
DP  - 2017 Apr
TI  - Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from 
      THP-1-derived macrophages.
LID - 10.1002/mnfr.201500960 [doi]
LID - 1500960
AB  - SCOPE: 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. METHODS AND RESULTS: Without affecting cell viability, 
      piperine concentration-dependently enhances ChE in THP-1-derived macrophages from 
      25 to 100 muM. 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. CONCLUSION: 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.
CI  - (c) 2016 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH 
      Verlag GmbH & Co. KGaA, Weinheim.
FAU - Wang, Limei
AU  - Wang L
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Palme, Veronika
AU  - Palme V
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Rotter, Susanne
AU  - Rotter S
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Schilcher, Nicole
AU  - Schilcher N
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Cukaj, Malsor
AU  - Cukaj M
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Wang, Dongdong
AU  - Wang D
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Ladurner, Angela
AU  - Ladurner A
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Heiss, Elke H
AU  - Heiss EH
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Stangl, Herbert
AU  - Stangl H
AD  - Institute of Medical Chemistry, Center for Pathobiochemistry and Genetics, 
      Medical University of Vienna, Vienna, Austria.
FAU - Dirsch, Verena M
AU  - Dirsch VM
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
FAU - Atanasov, Atanas G
AU  - Atanasov AG
AD  - Department of Pharmacognosy, University of Vienna, Vienna, Austria.
AD  - Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 
      Jastrzebiec, Poland.
LA  - eng
GR  - P 25971/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161223
PL  - Germany
TA  - Mol Nutr Food Res
JT  - Molecular nutrition & food research
JID - 101231818
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Alkaloids)
RN  - 0 (Benzodioxoles)
RN  - 0 (Piperidines)
RN  - 0 (Polyunsaturated Alkamides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Scavenger Receptors, Class B)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - U71XL721QK (piperine)
SB  - IM
MH  - ATP-Binding Cassette Transporters/*drug effects/metabolism
MH  - Algorithms
MH  - Alkaloids/*pharmacology
MH  - Atherosclerosis/metabolism
MH  - Benzodioxoles/*pharmacology
MH  - Biological Transport
MH  - Cell Survival/drug effects
MH  - Cholesterol/metabolism
MH  - Half-Life
MH  - Humans
MH  - Macrophages/*drug effects/metabolism
MH  - Piper nigrum/chemistry
MH  - Piperidines/*pharmacology
MH  - Polyunsaturated Alkamides/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Scavenger Receptors, Class B/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC5382977
MID - EMS71234
OTO - NOTNLM
OT  - ABCA1
OT  - Calpain
OT  - Cholesterol efflux
OT  - Macrophages
OT  - Piperine
EDAT- 2016/11/20 06:00
MHDA- 2017/11/14 06:00
PMCR- 2017/04/19
CRDT- 2016/11/19 06:00
PHST- 2015/11/25 00:00 [received]
PHST- 2016/10/24 00:00 [revised]
PHST- 2016/11/10 00:00 [accepted]
PHST- 2016/11/20 06:00 [pubmed]
PHST- 2017/11/14 06:00 [medline]
PHST- 2016/11/19 06:00 [entrez]
PHST- 2017/04/19 00:00 [pmc-release]
AID - MNFR2797 [pii]
AID - 10.1002/mnfr.201500960 [doi]
PST - ppublish
SO  - Mol Nutr Food Res. 2017 Apr;61(4):1500960. doi: 10.1002/mnfr.201500960. Epub 2016 
      Dec 23.