First Advisor
Yuyan Han
First Committee Member
Gregory DeKrey
Second Committee Member
David Hydock
Degree Name
Master of Science
Document Type
Thesis
Date Created
5-2025
Department
College of Natural and Health Sciences, Biological Sciences, Biological Sciences Student Work
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a prolific disease worldwide, with rising incidence and limited treatment options. The disease is progressive, what begins as simple lipid congestion within the cells of the liver eventually leads to incitement of inflammatory reactions and destruction of the liver which can further develop into cancer. Epidemiological data suggests that Cannabis use is associated with reduced incidence of NAFLD, and relatively recent changes in the plants legal status now affords us with the opportunity to investigate unstudied cannabinoids in the context of NAFLD. Further, growing popularity of these bioactive compounds as supplements warrants investigation into their safety and efficacy in the broad interest of public health. Research has primarily investigated the primary non-psychedelic compound Cannabidiol (CBD) which has proven benefits and as of 2018 is available as a prescription treatment for epilepsy. Cannabigerol (CBG) is the precursor to CBD and presents as a similar novel pharmacological agent. However, little is known about the therapeutic potential of CBG; the goal of this project is to examine CBG as a therapeutic agent in the context of NAFLD. We addressed this objective over the course of two different studies: 1.) Examining the efficacy of CBG as a chemotherapeutic agent against cholangiocarcinoma, 2.) Examining CBG as a potential anti-steatotic and anti-inflammatory agent in NAFLD. To investigate the effects of CBG on cholangiocarcinoma
we used an in-vitro model and established an effective concentration of CBG which was further used to evaluate the drugs capacity to inhibit proliferation, invasion and induce apoptosis in tumor cells. These experiments were run pairwise against CBD to contrast the effects of CBG against a known cannabinoid. To investigate the effects of CBG for anti-steatotic agent and immunomodulatory properties we used an in-vivo murine model fed with a high fat diet supplemented with CBG and then observed changes in liver phenotype. We further correlated the effects of CBG on lipid metabolism in an in-vitro model of human hepatoma cells. We found that CBG is able to inhibit tumor growth and induce changes in lipid handling within the liver. Our results implicate PPARγ as a target of CBG activity, which would place its therapeutic potential as an insulin sensitizing agent in the context of NAFLD. We can conclude that CBG has significant potential as an intervention in NAFLD, though further study is needed to fully elucidate the systemic effects of the drug and the influence of other receptor mechanisms implicated by the pharmacology of CBG which could be advantageous to therapy.
Abstract Format
html
Keywords
cannabidiol; cannabinoids; cholangiocarcinoma; female mouse model; circadian rhythm; hepatocellular carcinoma; high fat diet; cell based assay; hepatic mouse tissue
Language
English
Extent
107 pages
Rights Statement
Copyright is held by the author.
Digital Origin
Born digital
Recommended Citation
Viereckl, Michael J., "Evaluating Cannabigerol as a Therapeutic Agent in Non-Alcoholic Fatty Liver Disease" (2025). Master's Theses. 341.
https://digscholarship.unco.edu/theses/341
