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- 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.
- Authors
Lee, Ki Hoon; Jeong, Eui-Seon; Jang, Goeun; Na, Ju-Ryun; Park, Soyi; Kang, Wan Seok; Kim, Eun; Choi, Hakjoon; Kim, Jin Seok; Kim, Sunoh
- 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.
- Subjects
LIPID metabolism; CHOLESTEROL metabolism; ANIMAL experimentation; BENZOPYRANS; BIOLOGICAL models; CELLULAR signal transduction; GLYCOPROTEINS; HIGH density lipoproteins; IMMUNOBLOTTING; LIVER cells; MEDICINAL plants; OXIDOREDUCTASES; PHOSPHORYLATION; PHOSPHOTRANSFERASES; PROTEINS; RATS; TRANSCRIPTION factors; MALONDIALDEHYDE; PLANT extracts; IN vitro studies; IN vivo studies
- Publication
Nutrients, 2020, Vol 12, Issue 3, p610
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu12030610