Abstract
Objective: This work was designed to investigate the protection of cannabidiol (CBD) against palmitic acid (PA)-induced injury in cultured hepatocytes and the underlying mechanism associated with autophagic flux. Methods: Experiment 1: Primary cultured hepatocytes were stimulated with PA (800 μmol/L) and treated with CBD (5 μmol/L) and chloroquine (CQ, 50 nmol/L) or not for 24 hours (1: control group; 2: PA-stimulated group; 3: PA-stimulated group treated with CBD; 4: PA-stimulated group treated with CBD and CQ). Autophagic flux was evaluated by Western blot analysis. Apoptosis was measured by flow cytometry. The mRNA expression of genes involved in endoplasmic reticulum stress was determined by reverse transcription PCR. The mitochondrial function was determined by using fluorescent probe including Rh123 and lucigenin. Experiment 2: Primary cultured hepatocytes were treated with CBD alone for 24 h (1: control group; 2: lower-dose CBD-treated group; 3: higher-dose CBD-treated group). Then, the autophagic flux was evaluated by Western blot analysis. Results: When compared to control group, exposure to PA significantly led to impaired autopagic flux (evidenced by increased ratio of LC3-II/LC3-I and protein expression of p62), increased apoptosis, endoplasmic reticulum stress (evidenced by increased mRNA expression of C/EBP homologous protein, glucose-regulated protein 78, and X-box protein 1), and mitochondrial dysfunction (evidenced by reduced mitochondrial membrane potential and enhanced formation of mitochondrial reactive oxygen species). When compared to PA-stimulated group, CBD treatment significantly attenuated PA-induced impaired autophagic flux, apoptosis, endoplasmic reticulum stress, and mitochondrial dysfunction in cultured hepatocytes. The protection of CBD against PA was abolished by co-incubation with CQ. In addition, treatment with CBD alone had no significant effect on autophagic flux in cultured hepatocytes Conclusion: Cannabidiol attenuates palmitic acid-induced impaired autophagic flux, apoptosis, endoplasmic reticulum stress, and mitochondrial dysfunction in cultured hepatocytes through promoting autophagic flux.
Highlights
Nonalcoholic fatty liver disease refers to the elimination of alcohol, virus and other clear liver damage factors, which are caused by genetic, environmental and metabolic stress related factors that lead to the deposition of lipid in the liver cells, and lead to diffuse fatty degeneration of the liver cells
The results suggest that CBD can reduce PA induced hepatocyte apoptosis by promoting autophagy flow
Under PA stimulation, the activity of autophagic lysosome increased in hepatocytes, the rate of degradation and autophagic flow were destroyed, and CBD treatment could reduce the ratio of LC3-II/LC3-I in the liver cells and the protein expression of p62, suggesting that CBD may restore the autophagic flow destroyed by PA by promoting the degradation of autophagosomes
Summary
Nonalcoholic fatty liver disease (non-alcoholic fatty liver disease) refers to the elimination of alcohol, virus and other clear liver damage factors, which are caused by genetic, environmental and metabolic stress related factors that lead to the deposition of lipid in the liver cells, and lead to diffuse fatty degeneration of the liver cells. With the improvement of material life, nonalcoholic fatty liver disease is becoming more and more common as a chronic liver disease. It has attracted more and more attention from medical workers [1]. The medicinal value of cannabis has long been well known, its clinical application has been greatly restricted because of its addiction and psychogenic hallucination. Extraction found that the main active ingredient in cannabis is International Journal of Clinical and Experimental Medical Sciences 2018; 4(3): 51-56
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International Journal of Clinical and Experimental Medical Sciences
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
