Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/ijms24076060
Keywords
beta-caryophyllene; NAFLD; steatosis; lipid profile; CB2 receptors; PPAR gamma; PPAR alpha; HepG2 cell line
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Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease without approved pharmacological therapy. The study investigated the effects of (E)-beta-caryophyllene (BCP), a phytocannabinoid, on HepG2 steatotic hepatocytes. BCP was found to decrease lipid accumulation and change the lipid profile in steatotic conditions by reducing saturated fatty acids. The action of BCP was mediated by CB2 cannabinoid receptor, peroxisome proliferator-activated receptor alpha (PPAR alpha), and gamma (PPAR gamma). The results suggest potential applications of BCP in the treatment of NAFLD.
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)-beta-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 alpha (PPAR alpha) and gamma (PPAR gamma). Interestingly, BCP was able to counteract the increase in CB2 and the reduction in PPARa 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.
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