Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Recently, natural compounds that may be beneficial for improving NAFLD have received increasing attention. Artemisia annua L. is the source of antimalarial phytomolecule, artemisinin, which has been reported to prevent obesity. However, the effect of A. annua extract on hepatic lipid metabolism remains unclear. This study was performed to determine the protective effect of Artemisia annua extract (AAE) on high-fat diet (HFD)-induced hepatic lipid accumulation, and elucidate the molecular mechanisms behind its effects in vivo and in vitro. We found that HFD-fed mice with AAE administration (50 mg/kg/day) for 8 weeks dramatically reduced hepatic lipid accumulation compared to the control mice taken with HFD alone. The body and liver weights of AAE group were significantly lower than those of HFD group, and oral administration of AAE remarkably suppressed the serum levels of triglyceride (TG), total cholesterol (TC), fasting glucose, alanine transaminase (ALT) and aspartate transaminase (AST) in HFD-fed mice. AAE significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in the liver of HFD-fed mice and HepG2 hepatocytes. Moreover, AAE downregulated the hepatic expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) in HFD-fed mice and high glucose-treated HepG2 cells. In addition, the inhibitory effects of AAE on the overexpression of SREBP-1c and FAS were attenuated by compound C, which is the specific AMPK inhibitor, in high glucose-treated HepG2 cells. These results indicated that AAE may represent a promising approach for the prevention and treatment of obesity-related NAFLD via the activation of AMPK and the regulation of AMPK-dependent lipogenic genes.

Introduction
Materials and Methods
    시약
    개똥쑥추출물(Artemisia annua extract, AAE)의 제조
    고지방식이(High-fat diet, HFD)로 유도한 지방간 마우스모델 시험
    혈청생화학적 분석
    Hematoxylin & Eosin(H&E) 염색을 이용한 조직학적 분석
    세포 배양 및 세포독성시험
    High glucose로 지방증을 유도한 HepG2 세포 시험
    Nile red binding assay
    간세포 내 중성지방 및 총 콜레스테롤 측정
    Western blot analysis
    통계 분석
Results
    고지방식이 유도 지방간 마우스 모델에서 체중, 조직 무게및 혈청 지방 수준에 대한 AAE의 효과
    AAE에 의한 간 조직의 지방증(steatosis) 조절
    간의 지질대사 조절 인자에 대한 AAE의 영향
    AAE의 간세포 지방 축적 억제 효과
    AAE의 AMPK 의존적 지방 축적 억제 효과
Discussion
References

• Su-Jin Park(G&P Bioscience Co., Ltd.)
• Chul Yung Choi(Jeollanamdo Institute of Natural Resources Research)
• Jae-Cheon Jeong(Mokpo Marine Food-Industry Research Center)
• Rok-Kyoung Lee(Mokpo Marine Food-Industry Research Center)
• Yong-Pil Hwang(Department of Pharmaceutical Engineering, International University of Korea) Corresponding author