Effects of Tualang Honey on non-alcoholic steatohepatitis in rat model

Abstract

Non-alcoholic Steatohepatitis (NASH) is a common chronic liver disease that may progress to cirrhosis and hepatocellular carcinoma. Currently, there is limited therapy available. Tualang honey which is known for its anti-inflammatory and anti-oxidative effects may improve NASH as inflammatory process and oxidative damage have been implicated in the pathogenesis. However studies utilizing animal models induced with cholesterol diet ranging from 0.5 – 2% are hampered by inconsistent yield of NASH features as assessed histologically. The aims of this study are to establish NASH animal model utilizing 12% cholesterol diet and to investigate the effects of Tualang honey on NASH. This study is divided into 2 phases: the induction phase with cholesterol diet and the treatment phase with Tualang honey. In the induction phase, 42 Sprague-Dawley rats were randomly divided into standard diet (std) group (n=12) and NASH group (n=30). The 12 rats in the std group were fed with commercial rat pellet while the 30 rats in the NASH group were fed with 1% cholesterol (1% CD) diet for 14 weeks. The experiment was extended for an additional 6 weeks with increment of cholesterol in the diet from 1% to 12 % in the NASH group since the liver histology did not show features of NASH in the 1% CD. At the end of the additional 6 weeks period, liver histology showed NASH changes in the 12% CD. Subsequently in the treatment phase, the rats in the NASH group were randomly divided and continued on the cholesterol diet in addition to administration of 0.2, 1.2, 2.4 and 3.0 g of Tualang honey per kg body weight daily respectively as treatment for 4 weeks. Results of the histological sections of the livers of the 12% CD rats in the induction phase exhibited features consistent with NASH which include macrovesicular steatosis, occasional hepatocyte ballooning degeneration with mild to moderate lobular and portal inflammation. The 12% CD group revealed significantly increased serum alanine aminotransferase (ALT), serum insulin levels, homeostatic model assessment insulin resistance (HOMA-IR), serum total cholesterol (TC), serum low-density lipoprotein cholesterol (LDL-c) and reduced high-density lipoprotein cholesterol (HDL-c) in rats. Tualang honey supplementation in the treatment groups showed significant improvement in the histological grading and non-alcoholic fatty liver disease (NAFLD) activity scores. Tualang honey also significantly reduced serum ALT, serum insulin, HOMA-IR, serum LDL-c and increased HDL-c in NASH rats in these groups. In conclusion, this study has successfully induced mild – moderate NASH rat model utilizing 12% cholesterol diet and also demonstrated that Tualang honey administration improved histological grading, NAFLD activity score, insulin resistance, liver function and and dyslipidemia in NASH animal model.