ABSTRACT: Blue honeysuckle (BH, Lonicera caerulea) is used as a traditional medicine in Russia, Japan and China, but is not commonly considered as an edible berry in Europe, USA or Korea. BH has been revealed to decrease serum cholesterol and triacylglycerol (triglyceride or TG) levels through the activation of AMP?activated protein kinase (AMPK), thus it is expected to be a health functional food and pharmaceutical agent for the prevention of non?alcoholic liver damage, in addition to effects as a suppressor of hyperlipidemia and as an anti?obesity agent. In the present study, the pharmacological activity of BH extract (BHe) was observed in high?fat diet (HFD)?fed mice. Significant increases in fat pad weight, body weight, fat accumulation (body and abdominal fat density, and thickness of the periovarian and abdominal wall) and serum biochemical levels (aspartate transaminase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, ??glutamyltransferase, total cholesterol, low?density lipoprotein and TG, with the exception of high?density lipoprotein) were observed in HFD?fed mice. In addition, increases in adipocyte hypertrophy, the area of steatohepatitis and hepatocyte hypertrophy were observed, whereas decreased zymogen content was identified upon histopathological observation. Increased deterioration of the endogenous antioxidant defense system (liver catalase, glutathione and superoxide dismutase) and hepatic lipid peroxidation was observed. In addition, there were decreases in hepatic glucokinase activity, AMPK?1 and AMPK?2 mRNA expression, adipose tissue uncoupling protein 2 expression, and adiponectin mRNA expression, increases in phosphoenolpyruvate carboxykinase and glucose?6?phosphatase activity, hepatic acetyl?CoA carboxylase 1 mRNA expression, and the expression of leptin, CCAAT/enhancer?binding protein (C/EBP) ?, C/EBP? and sterol?regulatory?element?binding protein 1c mRNA in the periovarian tissue. Furthermore, non?alcoholic fatty liver disease (NAFLD) and obesity were significantly inhibited by the continuous administration of BHe for 84 days. These results revealed that BHe may be a promising novel drug or functional food candidate for the treatment of obesity and NAFLD.
