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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Grand Ballroom |
| Time |
10월 18일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-296 |
| Subject |
Epigallocatechin-3-Gallate (EGCG) Conjugated with Phenylalanine Shows Stimulation of Hepatic Autophagy and Lipid Clearance |
| Authors |
Yongmin Lee, Youhoon Chong1,*
department of Biotechnology, Konkuk University, Korea
1Department of Biotechnology, Konkuk University, Korea
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| Abstract |
(-)-Epigallocatechin gallate (EGCG) is known as an autophagy-enhancing and thereby lipid-lowering agent, and optimization of its activity warrants its therapeutic potential in the treatment of hepatic diseases as well as metabolic disorders. In this study, we investigated the autophagy-enhancing activity of 14 EGCG derivatives and, among those, E10 with a phenylalanine attached to the 4″-O-position of the EGCG scaffold showed the most promising effects in stimulating autophagy in Huh7 cells: 1) stimulation of autophagy was demonstrated by an increased amount of LC3B-II as well as the activation of a key enzyme for the initial autophagy process (AMP-activated protein kinase, AMPK) in the presence of E10; 2) E10-stimulated autophagic flux was confirmed by an increase in LC3B-II upon co-treatment with chloroquine (CQ), reduction of p62/SQSTM1, and increase in the formation of autophagic compartments visualized by both CYTO-ID staining and tandem RFP-GFP-LC3 fluorescence. Finally, the autophagy-inducing activity of E10 culminated in a reduction of hepatic lipid accumulation caused by fatty acids. In all of the assay settings performed in this study, E10 was consistently 1.3 to 3.5-fold more potent than EGCG. Taken together, we demonstrated a significant increase in autophagy stimulating activity of EGCG through structural modifications, which opens the door to an extensive structure-activity relationship study of the EGCG scaffold for the discovery of more potent autophagy enhancers. |
| E-mail |
jsa734@naver.com |
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122nd General Meeting of the KCS