Abstract

[Purpose]This study aimed to study the protective effects and mechanism of Blue Honeysuckle (BH) extracts (Berries of Lonicera caerulea L.) on non-alcoholic fatty liver disease (NAFLD) and obesity risk factors in a high fat-diet (HFD) model.[Methods]Animals adapted to HFD were selected after 1 week of adaption period and divided into 6 groups (8 mice in each group; 40 HFD-fed mice and 8 normal fat pellet diet (NFD)-fed mice). After the end of 12 weeks of continuous oral administrations of 3 different dosages of BH extract, 400, 200 and 100 mg/kg, or metformin 250 mg/kg, dissolved in a volume of 10 mL/kg distilled water, the hepatoprotective, hypolipidemic, hypoglycemic, nephroprotective, and anti-obesity effects were analyzed.[Results]The BH extract improved fat density and mass, adipocyte histopathology, hepatocyte hypertrophy, hepatic enzyme activity, lipid metabolism, and related gene expression including ACC1, AMPK α1 and AMPK α2 in hepatic tissue, leptin, UCP2, adiponectin, C/EBP α, C/EBPβ and SREBP1c in adipose tissue. Especially, 200 mg/kg of BH extract constantly improved NAFLD and obesity risk factors through AMPK upregulation-mediated hepatic glucose enzyme activity, lipid metabolism-related gene expression, and activation of the antioxidant defense system, to a level comparable to that of metformin 250 mg/kg in HFD-fed mice.[Conclusion]BH extract has the potential to reduce the risk factors associated with obesity, in addition to the remarkable effect of preventing NAFLD. Future research will need to be done to determine whether these results are consistent in human studies.

Highlights

  • In the past 30 years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing owing to changes in dietary habits and Western lifestyles in the Asia-Pacific region[1]

  • Adapted mice showed an increased regular body weight compared with healthy controls during the first week of high fat-diet (HFD) supply; the HFD control mice showed a significant increase in body weight when compared with intact mice from the first week after HFD supply (F=34.52, p

  • Significant decreases in body weights were detected in metformin 250 mg/kg-treated mice from 42 days after the start of administration, and from 35, 42 and 49 days after start of administration in Blue Honeysuckle (BH) extract 400, 200 and 100 mg/kg-treated mice when compared with the HFD control (F=9.144, p

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Summary

Introduction

In the past 30 years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing owing to changes in dietary habits and Western lifestyles in the Asia-Pacific region[1]. NAFLD is the most common chronic liver disease and is associated with an increase in serum alanine transaminase, as well as disorders such as benign macrovesicular hepatosteatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of the liver, and hepatocellular carcinoma[2]; increased triglyceride levels are associated with these tissue changes. The accumulated fat in NAFLD can increase oxidative stress[3] in the liver and cause chronic damage to it[4]. There is a growing interest in berries as a food for reducing oxidative stress caused by reactive oxygen species because berries have both antioxidant vitamins and enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase, as well as phytochemicals with distinct flavors, odors, and colors and antioxidant functions at the same time[5]. BH is known as haskap or hasukappu in Japan and zhimolost in Russia[7]

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