Nonalcoholic Steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) characterized by inflammation, fibrosis, steatosis, and oxidative stress, in addition to excessive fat accumulation in the liver. Cannabigerol (CBG), a precursor molecule of Cannabidiol (CBD), has demonstrated anti-inflammatory and anti-oxidative effects in various studies. Our previous data showed that a low dosage of CBG reduced inflammation and fibrosis in male NASH mice. However, the impact of CBG on female mice remains unknown. Recent studies have identified changes in immune cell populations in NAFLD patients. The goal of this project was to test the impact of CBG treatment in alleviating the risks related to methioninecholine deficient (MCD) diet induced NASH in female mice. Here, we evaluated the efficacy of low and high doses of CBG as a novel therapeutic option for ameliorating NASH-associated inflammation, ductular reaction, fibrosis, oxidative stress, and steatosis in a female mouse model induced by the MCD diet. We also determined changes in the immune cell population of nonparenchymal cells (NPC) caused by CBG treatment. Although there wasn't a significant change in the liver-to-body weight ratio of female mice, we observed an overall improvement in liver health, manifested as reduced leukocyte infiltration, after treatment with both low and high doses of CBG. The experimental mice that received CBG interventions did not exhibit significant changes in the heightened hepatic ballooning or steatosis observed in the MCD-treated NASH female mice. However, both low and high doses of CBG treatment significantly reduced fibrosis, oxidative stress, ductular proliferation, and inflammation levels. In the groups treated with low and high doses of CBG, we noted a considerable reduction in the number of monocytes and T lymphocytes. Moreover, we conducted a partial study on the CBG’s signaling pathway. We found that CBG downregulates the activation of mast cells, thereby inhibiting the release of transforming growth factor (TGF-β1). This, in turn, suppresses the activation of hepatic stellate cells, resulting in a reduction in collagen deposition and subsequently decreasing fibrosis and ductular proliferation. The results of this study provide valuable insights for designing future interventions in pre-clinical and clinical research, particularly concerning the potential use and dosage of CBG to address liver fibrosis and inflammation in female patients.
Joly, Raznin A., "INVESTIGATING THE THERAPEUTIC POTENTIAL OF CANNABIGEROL (CBG) IN FEMALE NONALCOHOLIC STEATOHEPATITIS (NASH) MOUSE MODEL" (2023). Master's Theses. 294.