Mechanisms
Ellagic acid from unripe Rubus coreanus extract lowers hepatic CETP and HMG-CoA activity while raising LCAT activity, reducing cholesterol in rats (Nutrients 2020)
Original title: Unripe Rubus coreanus Miquel Extract Containing Ellagic Acid Regulates AMPK, SREBP-2, HMGCR, and INSIG-1 Signaling and Cholesterol Metabolism In Vitro and In Vivo
The authors investigated the cholesterol-lowering mechanism of a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and its bioactive compound ellagic acid, previously shown to have hypocholesterolemic and anti-obesity activity, in hepatocytes and a high-cholesterol-diet rat model. Both 5-uRCK and ellagic acid significantly reduced liver and serum cholesterol. Hepatic activities of HMG-CoA reductase and cholesteryl ester transfer protein (CETP) were reduced, while hepatic LCAT activity was increased, alongside histological improvements and a significant decrease in aortic and serum MDA content. Immunoblotting showed 5-uRCK and ellagic acid induced hepatic AMPK phosphorylation, inhibiting HMGCR activity, while suppressing nuclear translocation and activation of SREBP-2, the key transcription factor driving cholesterol biosynthesis.
Original abstract
Our previous study demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) has hypo-cholesterolemic and anti-obesity activity. However, the molecular mechanisms of its effects are poorly characterized. We hypothesized that 5-uRCK 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-uRCK in both hepatocytes and a high-cholesterol diet (HCD)-induced rat model. Cholesterol in the liver and serum was significantly reduced by 5-uRCK and ellagic acid. The hepatic activities of HMG-CoA and CETP were reduced, and the hepatic activity of LCAT was increased by both 5-uRCK 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-uRCK or ellagic acid. Further immunoblotting analysis showed that AMPK phosphorylation in the liver was induced by 5-uRCK and ellagic acid, which activated AMPK, inhibiting the activity of HMGCR by inhibitory phosphorylation. In contrast, 5-uRCK 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-uRCK and its bioactive compound, ellagic acid, are useful alternative therapeutic agents to regulate blood cholesterol.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.