ABSTRACT
The ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that directly contributes to high-density lipoprotein (HDL) biogenesis by regulating the cellular efflux of cholesterol. Since ABCA1 plays a pivotal role in cholesterol homeostasis and HDL metabolism, identification of a novel substance that is capable of increasing its expression would be beneficial for the prevention and therapy of atherosclerosis. In the present study, we studied the effects of ethanolic extracts of Brazilian red propolis (EERP) on ABCA1 expression and cholesterol efflux in THP-1 macrophages. EERP enhanced PPARγ and liver X receptor (LXR) transcriptional activity at 5-15µg/ml, which was associated with upregulation of PPARγ and LXRα expression. It was also found that EERP increase the activity of the ABCA1 promoter, which is positively regulated by LXR. Consistent with these findings, treatment with EERP increased both mRNA and protein expression of ABCA1. Finally, EERP upregulated ApoA-I-mediated cholesterol efflux. Our results showed that EERP promote ApoA-I-mediated cholesterol efflux from macrophages by increasing ABCA1 expression via induction of PPARγ/LXR.
Subject(s)
ATP Binding Cassette Transporter 1/genetics , Cholesterol/metabolism , Macrophages/drug effects , Plant Extracts/pharmacology , Propolis/chemistry , ATP Binding Cassette Transporter 1/metabolism , Animals , Apolipoprotein A-I/drug effects , Apolipoprotein A-I/metabolism , Biological Transport/drug effects , Cattle , Cell Line , Cell Survival/drug effects , Humans , Liver X Receptors , Macrophages/metabolism , Models, Biological , Orphan Nuclear Receptors/drug effects , Orphan Nuclear Receptors/genetics , PPAR gamma/drug effects , PPAR gamma/genetics , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Promoter Regions, Genetic/drug effects , Promoter Regions, Genetic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription, Genetic/drug effectsABSTRACT
AIM OF THE STUDY: The aim of present study was to investigate the effects of ethanolic extracts of red propolis (EERP) on adipogenesis and evaluate the molecular basis for their anti-obesity effects. MATERIALS AND METHODS: We tested whether EERP alone could induce differentiation of 3T3-L1 cells, regulate the expression of adipocyte-specific genes and reverse inhibitory effects of TNF-α on their differentiation. Next, we performed a luciferase reporter gene assay to test whether EERP could enhance transcriptional activities of PPARγ and adiponectin promoter activities. RESULTS: EERP strongly induced differentiation of 3T3-L1 preadipocytes into adipocytes, and enhanced the PPARγ transcriptional activity and adiponectin promoter activity. In addition, EERP attenuated the inhibitory effect of TNF-α on adipocyte differentiation and adiponectin production in mature adipocytes. CONCLUSION: The present study indicates that EERP enhance differentiation of 3T3-L1 adipocytes in part by its potency of PPARγ activation and are capable of reversing inhibitory effects of TNF-α on adipocyte differentiation and adiponectin expression. These results suggest the value of EERP as a diet supplement for prevention and treatment of obesity and obesity-associated disorders.
Subject(s)
Adipocytes/drug effects , Adipogenesis/drug effects , Adiponectin/metabolism , Anti-Obesity Agents/pharmacology , PPAR gamma/metabolism , Plant Extracts/pharmacology , Propolis/pharmacology , 3T3-L1 Cells , Adipocytes/cytology , Adiponectin/genetics , Animals , Dalbergia/chemistry , Mice , PPAR gamma/genetics , Plant Extracts/analysis , Promoter Regions, Genetic , Propolis/chemistry , Transcriptional Activation/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
We have previously reported that Brazilian propolis extracts inhibited growth of HL-60 human myeloid leukemia cells, which is partly attributed to the induction of apoptosis associated with granulocytic differentiation. In this study, we isolated three compounds which induce granulocytic differentiation evaluated by nitroblue tetrazolium (NBT)-reducing assays from the water extract of propolis and identified as 4,5-di-O-caffeoylquinic, 3,5-di-O-caffeoylquinic, and 3,4-di-O-caffeoylquinic acids by NMR analysis. Cell growth inhibitory activity of these caffeoylquinic acids was found in HL-60 cell, which was mainly attributed to the induction of apoptosis. Furthermore, the potency of caffeoylquinic acid derivatives to induce granulocytic differentiation was examined in HL-60 cells. Caffeic, quinic, and chlorogenic acids had no effects on the NBT-reducing activity, while 3,4,5-tri-O-caffeoylquinic acid induced more than 30% of NBT-positive cells. These results suggest that the number of the caffeoyl groups bound to quinic acid plays an important role in the potency of the caffeoylquinic acid derivatives to induce granulocytic differentiation. This is the first report demonstrating that the caffeoylquinic acid derivatives induce granulocytic differentiation of HL-60 cells.
Subject(s)
Cell Differentiation/drug effects , Granulocytes/drug effects , Propolis/chemistry , Quinic Acid/analogs & derivatives , HL-60 Cells , Humans , Magnetic Resonance Spectroscopy , Quinic Acid/chemistry , Quinic Acid/pharmacologyABSTRACT
Honey bee propolis is rich in cinnamic acid derivatives. Baccharin and drupanin from Brazilian honey bee propolis are cinnamic acid derivatives that contain prenyl moieties. We previously isolated these two compounds and demonstrated that they induce an apoptotic event in several tumor cell lines. In this study, we examined the tumoricidal activity of baccharin and drupanin in mice allografted with sarcoma S-180 and also studied the genotoxic effects on normal splenocytes using the alkaline single cell gel (comet) assay. We found that both baccharin and drupanin effectively suppressed growth of the tumor. Furthermore, these compounds induced a significant genotoxic effect on the tumor cells in comparison with normal splenocytes. Thus, baccharin and drupanin are potent tumor suppressive components of honeybee propolis.