Preventive and therapeutic effects of compound ginkgo extract in rats with nonalcoholic steatohepatitis induced by high-fat, high-fructose diet

Abstract

Objective: To establish a rat model of nonalcoholic steatohepatitis (NASH), and to investigate the preventative and therapeutic effects of compound ginkgo extract against NASH. Methods: A total of 60 male Sprague-Dawley rats were fed with high-fat feed and 10% fructose water for 24 weeks to establish the rat model of NASH. The general behaviors of the rats were observed, and the body weight was recorded. Blood samples from the inferior vena cava and the liver were collected after the last administration to measure serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), as well as liver function parameters. The liver index was calculated, HE staining was performed to observe liver histopathological changes, and the total lipase activity and the levels of TC, TG, and free fatty acid (FFA) in liver tissue were measured. Results: After 24 weeks, compared with the normal group, the model group had a significantly faster increase in body weight, significant increases in serum levels of TC (2.20±0.52 mmol/L), TG (0.87±0.22 mmol/L), LDL-C (1.22±0.50 mmol/L), alanine aminotransferase (ALT) (129.4±44.7 U/L), and aspartate aminotransferase (AST) (209.3±42.8 U/L), liver index (3.62%±0.28%), and the levels of TC (4.42±1.39 mmol/mg.prot), TG (0.85±0.11 mmol/mg.prot), and FFA (644.78±36.65μmol/L) in liver tissue, and significant reductions in serum HDL-C level (0.58±0.11 mmol/L) and the activity of lipoprotein lipase (LPL) (9.95±1.64 U/mg.prot) and hepatic lipase (HL) (9.91±1.03 U/mg.prot) (allP< 0.01). In addition, the pathological results showed severe hepatocyte steatosis, varying degrees of inflammatory cell infiltration, exudation in the portal area, and necrosis of liver cells in the model group. After the intervention with compound ginkgo extract, there were significant reductions in serum levels of TC (1.78±0.21 mmol/L), TG (0.58±0.07 mmol/L), LDL-C (0.84±0.19 mmol/L), and ALT (84.1±17.1 U/L), AST (155.4±20.9 U/L), liver index (2.71%±0.15%), and the levels of TC (2.24±1.02 mmol/mg.prot), TG (0.46±0.11 mmol/mg.prot), and FFA (580.56±50.63μmol/L) in liver tissue, as well as significant increases in serum HDL-C level (0.68±0.10 mmol/L) and the activities of LPL (15.54±2.21 U/mg.prot) and HL (11.92±1.87 U/mg.prot) (P< 0.05 orP< 0.01). At the same time, it significantly reduced hepatomegaly in rats and improved fatty degeneration and degree of inflammation in liver cells. Conclusion: Compound ginkgo extract can prevent and treat NASH by correcting dyslipidemia, improving liver function and fatty degeneration in hepatocytes, and reducing the degree of inflammation, and its mechanism of action may be associated with increasing total lipase activity, reducing FFA in the liver, increasing the decomposition of TG, and reducing the synthesis of TG.