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Abstract Title:

Piperine inhibits ABCA1 degradation and promotes cholesterol efflux from THP-1-derived macrophages.

Abstract Source:

Mol Nutr Food Res. 2016 Nov 15. Epub 2016 Nov 15. PMID: 27862930

Abstract Author(s):

Limei Wang, Veronika Palme, Susanne Rotter, Nicole Schilcher, Malsor Cukaj, Dongdong Wang, Angela Ladurner, Elke H Heiss, Herbert Stangl, Verena M Dirsch, Atanas G Atanasov

Article Affiliation:

Limei Wang

Abstract:

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 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.

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.

Study Type : In Vitro Study

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Sayer Ji
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