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Pharmaceutica Analytica Acta | Volume: 09
September 20-22, 2018 Prague, Czech Republic
Pharmaceutics & Drug Delivery Systems
17th Annual Congress on
Enhancement inmitochondrial biogenesisby (-)-epigallocatechingallate (EGCG) throughconjugation
with a methyl-branched carbonate chain
Youhoon Chong
Konkuk University, South Korea
(-)-Epigallocatechin-3-gallate (EGCG) is known as a mitochondria-targeted molecule that can prevent mitochondrial
deterioration and induce mitochondrial biogenesis by modulating key regulators of mitochondrial metabolism. In this study,
we tackled whether derivatization of EGCG could result in enhancement of its effects on mitochondrial biogenesis. EGCG,
EGCG peracetate (AcEGCG), and its 4"-O-alkyl substituted congeners prepared by previously reported procedures were
biologically evaluated. Interestingly, EGCG and AcEGCG were only marginally effective in inducing mitochondrial biogenesis,
while AcEGCG congeners with an alkyl group at the 4"-O position showed significantly increased biological activity compared
to their parent compound. Among these series, compound 3f with a methyl-branched carbonate chain at the 4"-O position
of the AcEGCG scaffold showed the most enhancements in inducing mitochondrial biogenesis. Hepa1-6 cells treated with
3f exhibited increases in both mitochondrial mass (1.5 times) and relative mtDNA content to nDNA (1.5 times). As a
mitochondrial biogenesis enhancer, 3f also increased expression levels of regulators for mitochondrial function, including
PGC-1α (4.0 fold), p-AMPK (2.5 fold), SIRT1 (4.2 fold), ERRα (1.8 fold), NRF-1 (1.6 fold), NRF-2 (1.7 fold), and mtTFA (2.0
folds). Investigation of oxidative phosphorylation by mitochondria in the presence of 3f revealed that 3f increased NAD+/
NADH ratio, the amount of cytochrome C, ATP synthesis, and oxygen consumption in Hepa1-6 cells by 2.2, 1.4, 1.5, and 2.1
folds, respectively. Taken together, these results warrant extensive structure-activity relationship study for EGCG derivatives to
develop novel mitochondrial biogenesis enhancers.
Biography
Youhoon Chong has completed his PhD from University of Georgia, and Post-doctoral studies from The Scripps Research Institute. He is the Chairman of the
Department of Integrative Bioscience and Biotechnology, Konkuk University. He has published more than 140 papers in reputed journals.
Youhoon Chong, Pharm Anal Acta 2018, Volume: 9
DOI: 10.4172/2153-2435-C2-037