Ha, Taewoong Kim, Mi Kyoung Park, Kwang-su Jung, Woong Choo, Hyunah Chong, Youhoon 2024-01-19T23:01:35Z 2024-01-19T23:01:35Z 2021-09-03 2018-04-18 0021-8561 https://pubs.kist.re.kr/handle/201004/121469 (-)-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 mitochondria' 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, 3f with a methyl-branched carbonate chain at the 4 ''-O position of the AcEGCG scaffold showed the most enhancement in inducing mitochondrial biogenesis. Hepal 6 cells treated with 3f exhibited increases in both mitochondria' 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 mitochondria' function, induding PGC-1 alpha (4.0 fold), p-AMPK (2.5 fold), SIRT1 (4.2 fold), ERRa (1.8 fold), NRF-1 (1.6 fold), NRF-2 (1.7 fold), and mtTFA (1.6 folds). Investigation of oxidative phosphorylation by mitochondria in the presence of 3f revealed that 3f increased the NADVNADH ratio, the amount of cytochrome c, ATP synthesis, and oxygen consumption in Hepal 6 cells by 2.2, 1.4, 1.5, and 2.1 fold, respectively. Taken together, these results warrant an extensive structure activity relationship study for EGCG derivatives to develop novel mitochondrial biogenesis enhancers. English AMER CHEMICAL SOC TEA EPIGALLOCATECHIN-3-GALLATE EGCG PRODRUG SIRT1 BIOAVAILABILITY RESVERATROL CATECHINS PROTECTS PATHWAY CELLS Structural Modification of (-)-Epigallocatechin Gallate (EGCG) Shows Significant Enhancement in Mitochondrial Biogenesis Article 10.1021/acs.jafc.8b00364 1 JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, v.66, no.15, pp.3850 - 3859 JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 66 15 3850 3859 scie scopus 000430642200013 2-s2.0-85045514022 Agriculture, Multidisciplinary Chemistry, Applied Food Science & Technology Agriculture Chemistry Food Science & Technology Article TEA EPIGALLOCATECHIN-3-GALLATE EGCG PRODRUG SIRT1 BIOAVAILABILITY RESVERATROL CATECHINS PROTECTS PATHWAY CELLS (-)-EGCG structural modification mitochondrial biogenesis antiaging