Undescribed Phenylpropanoid-Substituted Ester-Type Catechins from Green Tea Exert Antiaging Effects in Caenorhabditis elegans via Activating DAF-16, HSF-1, and Heat Shock Proteins

作者：Zi Yang, Yuxing Zhang, Na Song, Chen‐Hui Chen, Hao Li, Mariam Fatima, Shuxin Li, Jing-Ya Yu, Yi Yang, Jiayi Li, Peng Zhang, Zhijun Liu, Jiazheng Liu, Guangmin Yao, Guan‐Hu Bao · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.5c02825 · 被引用次数：6 · 研究领域：Tea Polyphenols and Effects、Tryptophan and brain disorders、Protein Hydrolysis and Bioactive Peptides

Green tea processing creates a hot acidic environment that facilitates reactions between catechins and hydroxycinnamic acids (HCAs), generating new catechins. Accordingly, we developed a one-pot method incorporating a Michael addition reaction to synthesize 13 phenylpropanoid-substituted ester-type catechins (PSECs), whose contents exhibit seasonal changes in tea leaves similar to those observed for common catechins. These PSECs showed antiaging effects in Caenorhabditis elegans ( C. elegans ), among which PSEC13 extended the longest lifespan by 57%, formed through the reaction between sinapic acid and EGCG with an S configuration. Moreover, PSEC13 activated the HSF-1/DAF-16 axis, upregulating heat shock proteins (HSPs). Surface plasmon resonance (SPR) analysis confirmed high-affinity binding between PSEC13 and HSP-16.2 ( K D = 0.11 μM). Molecular dynamics simulations revealed that PSEC13 forms stable hydrogen bonds with key residues (GLU 39, SER 41, ASN 55 ) in the HSP-16.2 active site. This study emphasizes the potential of PSEC13 as a novel approach to enhance proteostasis and extend lifespan through the modulation of HSP-16.2.