B&Tech Co., Ltd., Central R&D Center, Gwangju 61239, Korea.
Nutrients. 2020 Feb 26;12(3):610. doi: 10.3390/nu12030610.
Our previous study demonstrated that a 5% ethanol extract of unripe (5-RCK) has hypo-cholesterolemic and anti-obesity activity. However, the molecular mechanisms of its effects are poorly characterized. We hypothesized that 5-RCK and one of its major bioactive compounds, ellagic acid, decrease cellular and plasma cholesterol levels. Thus, we investigated the hypocholesterolemic activity and mechanism of 5-RCK in both hepatocytes and a high-cholesterol diet (HCD)-induced rat model. Cholesterol in the liver and serum was significantly reduced by 5-RCK and ellagic acid. The hepatic activities of HMG-CoA and CETP were reduced, and the hepatic activity of LCAT was increased by both 5-RCK extract and ellagic acid, which also caused histological improvements. The MDA content in the aorta and serum was significantly decreased after oral administration of 5-RCK or ellagic acid. Further immunoblotting analysis showed that AMPK phosphorylation in the liver was induced by 5-RCK and ellagic acid, which activated AMPK, inhibiting the activity of HMGCR by inhibitory phosphorylation. In contrast, 5-RCK and ellagic acid suppressed the nuclear translocation and activation of SREBP-2, which is a key transcription factor in cholesterol biosynthesis. In conclusion, our results suggest that 5-RCK and its bioactive compound, ellagic acid, are useful alternative therapeutic agents to regulate blood cholesterol.
我们之前的研究表明，未成熟的 5%乙醇提取物（5-RCK）具有降胆固醇和抗肥胖活性。然而，其作用的分子机制尚未得到充分描述。我们假设 5-RCK 及其主要生物活性化合物鞣花酸可降低细胞内和血浆胆固醇水平。因此，我们在肝细胞和高胆固醇饮食（HCD）诱导的大鼠模型中研究了 5-RCK 的降胆固醇活性和机制。5-RCK 和鞣花酸均可显著降低肝脏和血清中的胆固醇。HMG-CoA 和 CETP 的肝活性降低，LCAT 的肝活性增加，这也导致组织学改善。口服 5-RCK 或鞣花酸后，主动脉和血清中的 MDA 含量显著降低。进一步的免疫印迹分析表明，5-RCK 和鞣花酸诱导肝脏中 AMPK 的磷酸化，从而激活 AMPK，通过抑制磷酸化抑制 HMGCR 的活性。相比之下，5-RCK 和鞣花酸抑制胆固醇生物合成的关键转录因子 SREBP-2 的核转位和激活。总之，我们的结果表明，5-RCK 及其生物活性化合物鞣花酸是调节血液胆固醇的有用替代治疗药物。
