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Tea drinking impacts aging and aging-related diseases. However, knowledge of anti-aging molecules other than the major catechins in complex tea extracts remains limited. Here we used Caenorhabditis elegans to analyze the longevity effects of tea extracts and constituents comprehensively. We found that the hot water extract of green tea prolonged lifespan and heathspan. Further, the MeOH fraction prolonged lifespan significantly longer than other fractions. Correlation analysis between mass spectroscopic data and anti-aging activity suggests that ester-type catechins (ETCs) are the major anti-aging components, including 4 common ETCs, 6 phenylpropanoid-substituted ester-type catechins (PSECs), 5 cinnamoylated catechins (CCs), 7 ester-type flavoalkaloids (ETFs), and 4 cinnamoylated flavoalkaloids (CFs). CFs (200 μM) are the strongest anti-aging ETCs (with the longest 73% lifespan extension). Green tea hot water extracts and ETCs improved healthspan by enhancing stress resistance and reducing ROS accumulation. The mechanistic study suggests that they work by multiple pathways. Moreover, ETCs modulated gut microbial homeostasis, increased the content of short-chain fatty acids, and reduced fat content. Altogether, our study provides new evidence for the anti-aging benefits of green tea and insights into a deep understanding of the chemical truth and multi-target mechanism., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guan-Hu Bao reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

SARS-CoV-2 M pro (Mpro) is the critical cysteine protease in coronavirus viral replication. Tea polyphenols are effective M pro inhibitors. Therefore, we aim to isolate and synthesize more novel tea polyphenols from Zhenghedabai (ZHDB) white tea methanol-water (MW) extracts that might inhibit COVID-19. Through molecular networking, 33 compounds were identified and divided into 5 clusters. Further, natural products molecular network (MN) analysis showed that MN1 has new phenylpropanoid-substituted ester-catechin (PSEC), and MN5 has the important basic compound type hydroxycinnamoylcatechins (HCCs). Thus, a new PSEC (1, PSEC636) was isolated, which can be further detected in 14 green tea samples. A series of HCCs were synthesized (2-6), including three new acetylated HCCs (3-5). Then we used surface plasmon resonance (SPR) to analyze the equilibrium dissociation constants (K D ) for the interaction of 12 catechins and M pro . The K D values of PSEC636 (1), EGC-C (2), and EC-CDA (3) were 2.25, 2.81, and 2.44 μM, respectively. Moreover, compounds 1, 2, and 3 showed the potential M pro inhibition with IC 50 5.95 ± 0.17, 9.09 ± 0.22, and 23.10 ± 0.69 μM, respectively. Further, we used induced fit docking (IFD), binding pose metadynamics (BPMD), and molecular dynamics (MD) to explore the stable binding pose of M pro -1, showing that 1 could tightly bond with the amino acid residues THR 26 , HIS 41 , CYS 44 , TYR 54 , GLU 166 , and ASP 187 . The computer modeling studies reveal that the ester, acetyl, and pyrogallol groups could improve inhibitory activity. Our research suggests that these catechins are effective M pro inhibitors, and might be developed as therapeutics against COVID-19., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guan-Hu Bao has patent # CN113429372A pending to Anhui Agricultural University., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Previous studies suggest that major Camellia sinensis (tea) catechins can inhibit 3-chymotrypsin-like cysteine protease (3CLpro), inspiring us to study 3CLpro inhibition of the recently discovered catechins from tea by our group., Methods: Autodock was used to dock 3CLpro and 16 tea catechins. Further, a 3CLpro activity detection system was used to test their intra and extra cellular 3CLpro inhibitory activity. Surface plasmon resonance (SPR) was used to analyze the dissociation constant (K D ) between the catechins and 3CLpro., Results: Docking data suggested that 3CLpro interacted with the selected 16 catechins with low binding energy through the key amino acid residues Thr24, Thr26, Asn142, Gly143, His163, and Gln189. The selected catechins other than zijuanin D (3) and (-)-8-(5''R)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (11) can inhibit 3CLpro intracellularly. The extracellular 3CLpro IC 50 values of (-)-epicatechin 3-O-caffeoate (EC-C, 1), zijuanin C (2), etc-pyrrolidinone C and D (6), etc-pyrrolidinone A (9), (+)-gallocatechin gallate (GCG), and (-)-epicatechin gallate (ECG) are 1.58 ± 0.21, 41.2 ± 3.56, 0.90 ± 0.03, 46.71 ± 10.50, 3.38 ± 0.48, and 71.78 ± 8.36 µM, respectively. The K D values of 1, 6, and GCG are 4.29, 3.46, and 3.36 µM, respectively., Conclusion: Together, EC-C (1), etc-pyrrolidinone C and D (6), and GCG are strong 3CLpro inhibitors. Our results suggest that structural modification of catechins could be conducted by esterificating the 3-OH as well as changing the configuration of C-3, C-3''' or C-5''' to discover strong SARS-CoV-2 inhibitors., (Copyright © 2021. Published by Elsevier GmbH.)

Formation of catechins-human serum albumin (HSA) complex contributes to stably transporting catechins and regulating their bioavailability. Recently, a new class of catechins namely flavoalkaloids have been reported from tea. The unique structural modification with an N-ethyl-2-pyrrolidinone ring at catechins from these flavoalkaloids has raised our interest in their HSA binding affinity. Thus, we investigated the interaction between HSA and flavoalkaloids by molecular docking, UV-Vis spectroscopy (UV), fluorescence quenching approaches, and surface plasmon resonance (SPR). Thermodynamic parameters suggest that electrostatic forces contribute greatly to the interaction. The binding ability is affected by different ester group (galloyl or cinnamoyl) at 3-OH, N-ethyl-2-pyrrolidinone substituted position (C-6 or C-8), C-2, C-3 and C-5''' configurations, and hydroxyl group numbers at B ring, among which the 3-O-cinnamoyl substitution and 5'''-R configuration present the strongest contributions. UV showed slight changes in the conformation and microenvironment of HSA during the binding process. The quenching and binding constants suggest that the quenching is a static type. The small K D values (1-20 μM) detected by SPR confirmed the strong binding affinities between HSA and flavoalkaloids. Present study will help us to understand the interaction mechanism between flavoalkaloids and HSA, shedding light on structural modification of common catechins to enhance the stability, bioavailability and bioactivities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Zijuan tea ( Camellia sinensis var. assamica), an anthocyanin-rich cultivar with purple leaves, is a valuable material for manufacturing tea with unique color and flavor. In this paper, four new phenylpropanoid substituted epicatechin gallates (pECGs), Zijuanins A-D (1-4), were isolated from Zijuan green tea by different column chromatography. Their structures were identified by extensive high resolution mass spectroscopy (HR-MS), nuclear magnetic resonance (NMR), and experimental and calculated circular dichroism (CD) spectroscopic analyses. Detection of the changes in fresh tea leaves collected from April to September and the final processed product by high performance liquid chromatography (HPLC)-HRMS suggested that production of compounds 1 and 2 may be enhanced by the processing procedure of Zijuan green tea. Additionally, 1-4 were proposed to be synthesized through interaction between the abundant secondary metabolite ECG and phenolic acids from tea leaves by two key steps of phenol-dienone tautomerism. 1 and 2 showed impressive activity in protecting SH-SY5Y cells against H 2 O 2 -induced damage at the concentration of 1.0 μM.

Tea is thought to alleviate neurotoxicity due to the antioxidative effect of ester-type tea catechins (ETC). Neutrophil gelatinase-associated lipocalin (NGAL) can sensitize β-amyloid (Aβ) induced neurotoxicity, and inhibitors of NGAL may relieve associated symptoms. As such, the interactions of ETC with NGAL were investigated by fluorescence spectrometry and molecular simulation. NGAL fluorescence is quenched regularly when being added with six processing types of tea infusion (SPTT) and ETC. Thermodynamic analyses suggest that ETC with more catechol moieties has a stronger binding capacity with NGAL especially in the presence of Fe 3+ . (-)-Epicatechin 3-O-caffeoate (ECC), a natural product isolated from Zijuan green tea, shows the strongest binding ability with NGAL (K d = 15.21 ± 8.68 nM in the presence of Fe 3+ ). All ETC are effective in protecting nerve cells against H 2 O 2 or Aβ 1-42 induced injury. The inhibitory mechanism of ETC against NGAL supports its potential use in attenuation of neurotoxicity.