Abstract
BACKGROUND: This study investigated the effects of cannabidiol (CBD) on early-stage inflammation, a key factor in the progression of liver diseases from metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH) and irreversible cirrhosis. The study focused on CBD's influence on the pro-inflammatory n-6 and anti-inflammatory n-3 pathways, on arachidonic acid (AA) levels as an early marker of inflammation, and the expression of enzymes involved in AA metabolism, as well as inflammatory cytokines and chemokines. METHODS: Forty male Wistar rats were randomly divided into four groups: control (C)-fed a standard diet and treated with cannabidiol vehicle for the last 14 days, control + cannabidiol (C + CBD) - fed a standard diet and treated with CBD for the last 14 days, high-fat diet (HFD) - fed a high-fat diet and treated with cannabidiol vehicle for the last 14 days, high-fat diet + cannabidiol (HFD + CBD)-fed a high-fat diet and treated with cannabidiol for the last 14 days. At the end of the treatment period, all the rats were fasted for 24 h, anesthetized, and sacrificed. Gas-liquid chromatography was used to measure n-6 and n-3 pathway polyunsaturated fatty acids (PUFAs) activities and AA levels in lipid fractions in the liver. The Multiplex immunoassay assessed cytokine and chemokine content in liver tissue, while Western Blot analyzed the expression of selected enzymes. RESULTS: Initial findings indicated CBD's potential in reducing inflammation and its therapeutic efficacy in preventing MASH development induced by HFD. The results indicated that supplementing with CBD led to a decrease in the n-6 PUFA pathway, known for its pro-inflammatory effects, and an increase in the anti-inflammatory n-3 PUFA pathway. These changes were simultaneous with lower levels of arachidonic acid, which is crucial for the formation of inflammatory mediators. CBD influenced the expression of enzymes like COX-1 and COX-2 involved in AA metabolism and reduced the levels of pro-inflammatory cytokines. CONCLUSIONS: Our observations confirmed that CBD, which affects early indicators of inflammation, has the potential to become a new and safe, promising supportive drug for hepatic inflammation and steatosis treatment.