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.
Subject(s)
ATP-Binding Cassette Transporters/drug effects , Alkaloids/pharmacology , Benzodioxoles/pharmacology , Macrophages/drug effects , Piperidines/pharmacology , Polyunsaturated Alkamides/pharmacology , ATP-Binding Cassette Transporters/metabolism , Algorithms , Atherosclerosis/metabolism , Biological Transport , Cell Survival/drug effects , Cholesterol/metabolism , Half-Life , Humans , Macrophages/metabolism , Piper nigrum/chemistry , RNA, Messenger/metabolism , Scavenger Receptors, Class B/metabolism , Up-Regulation/drug effectsABSTRACT
Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, and taxifolin, on the expression of ABCA1, an important cholesterol efflux transporter, in THP-1-derived macrophages. Four of the studied compounds, isosilybin A, silybin B, silychristin and isosilychristin, were found to significantly induce ABCA1 protein expression without affecting cell viability. Moreover, isosilybin A, a partial PPARγ agonist, was found to promote cholesterol efflux from THP-1 macrophages in a concentration-dependent manner. These findings first show ABCA1 protein up-regulating activity of active constituents of silymarin and provide new avenues for their further study in the context of cardiovascular disease.
Subject(s)
ATP Binding Cassette Transporter 1/metabolism , Macrophages/metabolism , Silymarin/pharmacology , Cell Line , Cell Survival/drug effects , Gene Expression Regulation/drug effects , Humans , Macrophages/cytology , Silymarin/chemistryABSTRACT
As a result of the continuous change in the design and function of consumer electrical and electronic products, the mechanical and material properties of the obsolete products, called waste electric and electronic equipment (WEEE), are highly variable. The variability within WEEE is explained by the number of different appliances, and the heterogeneity in composition of any given appliance. This paper reports on an extended investigation of the properties of WEEE, in particular small appliances. The investigation focuses on the analysis of the composition of about 700 single appliances. Firstly, analytical methods to characterize the waste equipment are described. The results of the experimental analyses show that the mechanical properties, the material composition, the polymer composition and the chemical composition of WEEE vary not only between equipment types with different functions, but also between single appliances within one equipment type. Data on hazardous and valuable substances in selected equipment types are presented. Using detailed data on the composition of individual appliances to calculate rates of recovery for assumed recycling processes demonstrates that the performance of recycling processes depends strongly on the composition of WEEE. Recycling-oriented characterization is, therefore, a systematic approach to support the design and the operation of recycling processes.
