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Master of Science

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Non-Alcoholic Steatohepatitis (NASH) is the advanced and more aggressive form of Non-Alcoholic Fatty Liver Disease (NAFLD). NASH is associated with severe hepatic fibrosis and inflammation. Methionine/choline deficient (MCD) high fat diet is known to induce NASH in a short period of time without showing signs of metabolic syndrome. Cannabigerol (CBG) is a plant-derived, non-psychotropic cannabinoid that has a potential anti-inflammatory effect. Other hemp extracts reduce the progression of NAFLD to NASH, whereas the impact of CBG on NASH is still unknown. Therefore, these studies aim to 1. Evaluate the therapeutic potential of CBG on reducing hepatic steatosis and fibrosis. 2. Evaluate the anti-inflammatory effect of CBG in MCD-induced NASH C57BL/6 male mice. 3. Evaluate how CBG interacts with CB1 and CB2 receptors. Liver tissues were harvested from C57BL/6 mice (n = 36) fed with MCD or high fat control (CTR) diets for three weeks then the mice were divided into three sub-groups and injected with a vehicle solution, low or high dose of CBG for two additional weeks. Body weight, liver-to-body weight ratio, serum chemistry and H&E staining were also measured to evaluate the overall health of mice, liver function and morphology. Moreover, various histological tests were performed to evaluate collagen deposition, inflammation, and fat deposition. In addition, the expression of cannabinoid receptors was evaluated using immunofluorescence staining. It is concluded that MCD diet caused a significant body weight loss in mice, while CBG administration showed a trend towards recovery of their body weight, liver-to-body weight ratio, as well as ALT levels in MCD diet group. Further, inflammation decreased with low CBG treatment but increased when treated with a high dose of CBG in both the CTR and MCD groups. Similarly, the expression of cannabinoid (CB) receptors 1 and 2 showed increased expression with high dose CBG, but alleviated expression with low CBG dose intervention in MCD group. Collectively, low dose of CBG can reduce fibrosis and inflammation in MCD-induced NASH. CBG is gaining traction as a commercially available supplement with a variety of health-related claims. These results will provide rigorously controlled pre-clinical data to guide future intervention studies in humans addressing the potential uses of CBG for inflammatory liver pathologies.

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