Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Int J Mol Med. 2015 Mar;35(3):803-9. doi: 10.3892/ijmm.2015.2074. Epub 2015 Jan 21.
Non-alcoholic fatty liver disease (NAFLD) is characterized by the hepatic manifestation of metabolic syndrome and is the leading cause of chronic liver disease. Steatohepatitis plays a critical role in the process resulting in liver fibrosis and cirrhosis. Puerarin is a herbal product widely used in Asia, and is believed to have therapeutic benefits for alleviating the symptoms of steatohepatitis. The present study was designed to investigate the effects and mechanisms of action of puerarin in reducing lipid accumulation in oleic acid (OA)-treated HepG2 cells. Hepatocytes were treated with OA with or without puerarin to observe lipid accumulation by Oil Red O staining. We also examined hepatic lipid contents (e.g., triacylglycerol and cholesterol) following treatment with puerarin. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to measure sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), peroxisome proliferator-activated receptor α (PPARα) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) protein and mRNA expression, respectively. Our results revealed that puerarin suppressed OA-induced lipid accumulation, and reduced the triacylglycerol and cholesterol levels. Furthermore, puerarin decreased the expression levels of lipogenic enzymes, such as FAS and SREBPs, and increased the expression levels of PPARα, which are critical regulators of hepatic lipid metabolism through the AMPK signaling pathway. These results indicate that puerarin has the same ability to activate AMPK, and reduce SREBP-1 and FAS expression, thus inhibiting hepatic lipogenesis and increasing hepatic antioxidant activity. We found that puerarin exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in hepatocytes. Therefore, puerarin extract may have therapeutic benefits in the treatment of fatty liver and lipid-related metabolic disorders.
非酒精性脂肪性肝病（NAFLD）的特征是代谢综合征的肝脏表现，是慢性肝病的主要原因。脂肪性肝炎在导致肝纤维化和肝硬化的过程中起着关键作用。葛根素是一种在亚洲广泛使用的草药产品，被认为具有缓解脂肪性肝炎症状的治疗作用。本研究旨在探讨葛根素降低油酸（OA）处理的 HepG2 细胞中脂质积累的作用及其机制。用 OA 处理肝细胞，或用 OA 加葛根素处理肝细胞，通过油红 O 染色观察脂质积累。我们还观察了用葛根素处理后肝内脂质含量（如三酰甘油和胆固醇）的变化。采用 Western blot 分析和逆转录-聚合酶链反应（RT-PCR）分别检测固醇调节元件结合蛋白-1（SREBP-1）、脂肪酸合酶（FAS）、过氧化物酶体增殖物激活受体α（PPARα）和腺苷 5'-单磷酸（AMP）激活的蛋白激酶（AMPK）的蛋白和 mRNA 表达。结果表明，葛根素抑制 OA 诱导的脂质积累，降低三酰甘油和胆固醇水平。此外，葛根素降低了脂肪生成酶如 FAS 和 SREBPs 的表达水平，增加了 PPARα 的表达水平，这是通过 AMPK 信号通路调节肝内脂质代谢的关键调节因子。这些结果表明，葛根素具有激活 AMPK 的相同能力，降低 SREBP-1 和 FAS 的表达，从而抑制肝内脂质生成和增加肝内抗氧化活性。我们发现，葛根素通过减少肝细胞内的脂肪生成来发挥调节脂质积累的作用。因此，葛根素提取物可能对治疗脂肪肝和与脂质相关的代谢紊乱具有治疗作用。
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