Therapeutic effect of cannabidiol on methionine-choline deficient diet-induced nonalcoholic steatohepatitis in rats and its mechanism / 解放军医学杂志

ABSTRACT

Objective To observe whether treatment with cannabidiol (CBD) affect nonalcoholic steatohepatitis (NASH) induced by methionine choline-deficient diet (MCD) in rats and investigate the underlying molecular mechanism. Methods Sixty-three adult male SD rats were randomly divided in to three groups as follows: Control group (rats fed with normal diet), MCD group (rats fed with MCD and MCD+CBD group [rats fed with MCD and treated with cannabidiol, 2mg/(kg.d), i.p.]. Ten weeks later, steatohepatitis and fibrosis were evaluated by hematoxylin-eosin and Masson staining, respectively. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured by using an automatic biochemical analyzer and hepatic levels of cholesterol and triacylglycerol were determined with kits. Autophagic flux in livers was evaluated by Western blotting. Results Treatment with cannabidiol reduced ratio of liver/body weightratio (4.2%±0.6% versus 3.1%±0.6%, P<0.05), histological scores (4.7±1.1 versus 2.2±0.5, P<0.05) and fibrosis (1.4%±0.4% versus 0.8%±0.3%, P<0.05) in rat livers, lowered levels of ALT (214.5±54.1U/L versus 92.1±36.0U/L, P<0.05) and AST (175.9±55.2U/L versus 70.8±24.9U/L, P<0.05) in serum, attenuated hepatic fat accumulation (cholesterol, 182.4±42.7mmol/mg protein versus 101.0±33.8mmol/mg protein, P<0.05; triglyceride, 71.4±12.5mmol/mg protein versus 38.7±11.1mmol/mg protein, P<0.05), and down-regulated mRNA expression of Col1A1 (2.9±0.4 versus 1.6±0.3, P<0.05) in livers of rats fed with MCD. Furthermore, cannabidiol led to the LC3 turnover (LC3-Ⅱ/LC3-I, 37.1±10.8 versus 71.2±17.1, P<0.05) and p62 decrease (202.4±40.9 versus 125.8±32.7, P<0.05) in the livers of MCD-fed rats. Conclusion Treatment with cannabidiol could relieve MCD-induced NASH in rats, at least in part, by autophagic flux promotion.