| Autor: |
Scandiffio R; Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy.; Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Quarello 15/a, 10135 Turin, Italy., Bonzano S; Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy.; Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano, 10043 Turin, Italy., Cottone E; Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy., Shrestha S; Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy., Bossi S; Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Quarello 15/a, 10135 Turin, Italy., De Marchis S; Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy.; Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano, 10043 Turin, Italy., Maffei ME; Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Quarello 15/a, 10135 Turin, Italy., Bovolin P; Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy. |
| Abstrakt: |
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease; however, no specific pharmacological therapy has yet been approved for this condition. Plant-derived extracts can be an important source for the development of new drugs. The aim of this study was to investigate the effects of (E)-β-caryophyllene (BCP), a phytocannabinoid recently found to be beneficial against metabolic diseases, on HepG2 steatotic hepatocytes. Using a fluorescence-based lipid quantification assay and GC-MS analysis, we show that BCP is able to decrease lipid accumulation in steatotic conditions and to change the typical steatotic lipid profile by primarily reducing saturated fatty acids. By employing specific antagonists, we demonstrate that BCP action is mediated by multiple receptors: CB2 cannabinoid receptor, peroxisome proliferator-activated receptor α (PPARα) and γ (PPARγ). Interestingly, BCP was able to counteract the increase in CB2 and the reduction in PPARα receptor expression observed in steatotic conditions. Moreover, through immunofluorescence and confocal microscopy, we demonstrate that CB2 receptors are mainly intracellularly localized and that BCP is internalized in HepG2 cells with a maximum peak at 2 h, suggesting a direct interaction with intracellular receptors. The results obtained with BCP in normal and steatotic hepatocytes encourage future applications in the treatment of NAFLD. |
