Jin Li,Jian Zeng,Jinming Peng,Yangyang Jia,Chun-Mei Li
A-type epigallocatechin-3-gallate (EGCG) and epicatechin-3-O-gallate (ECG) dimers have multiply biological activities. In this study, the pharmacokinetics of them were investigated in mice after a single dose intravenous administration, and the metabolites in mice plasma and urine were investigated by ultra-performance liquid chromatography-Quadrupole-time of flight mass spectrometer (UPLC-QTOF-MS). Our results showed that the half-life (t1/2) of A-type EGCG and ECG dimers were 116.37 min and 33.04 min, respectively, and the maximal concentration in plasma was 32.81 μg/mL and 55.59 μg/mL, respectively. It was found that two dimers were firstly experienced by quinone methide (QM) fission to form the EGCG and ECG analogue, and the phase II metabolites were generated subsequently. The main metabolites in plasma and urine were glucuronidation and sulphation derivatives. In addition, small molecule weight of phenolic acids were detected in urine.
Ying Zhang,Li Zhong,Bin Zhou,Jin-yu Chen,Chun-mei Li
To more fully understand the mechanism by which persimmon tannin (PT) inhibited phospholipase A 2 (PLA 2 ) and the structural requirements of PT for the inhibition, the interactions between PLA 2 and seven characteristic structural elements of PT including epigallocatechin-3-gallate (EGCG), myricetin, epicatechin-3-gallate (ECG), epicatechin-3-gallate-(4β → 8, 2β → O → 7)-epicatechin-3-gallate (A-type ECG dimer), epigallocatechin-3-gallate-(4β → 8, 2β → O → 7)-epigallocatechin-3-gallate (A-type EGCG dimer), epicatechin-(4β → 8, 2β → O → 7)-epicatechin (A-type EC dimer) and epicatechin-(4β → 8)-epicatechin (B-type EC dimer) were studied by enzymatic and spectroscopic methods. Molecular docking was also used to explore the possible residues involved in the interactions. The results revealed that A-type EGCG dimer and A-type ECG dimer showed higher inhibitory effects on the catalytic activity of PLA 2 than monomers and B-type dimer. They induced greater conformational changes in PLA 2 than other structural elements. In addition, molecular docking studies revealed that expect for lysine residues, other residues such as Trp18, Try27, Gly29, His47 and Tyr63 were involved in the interactions. We propose that A-type EGCG and ECG dimer units may be structural requirements for the interaction between PT and PLA 2 . Our data provide an additional structural basis for anti-PLA 2 activity of persimmon tannin.
Rong-zu Nie,Wei Zhu,Jin-ming Peng,Zhen-zhen Ge,Chun-mei Li
In the present study, the disruptive effects of epigallocatechin-3-gallate (EGCG) and A-type dimeric epigallocatechin-3-gallate (A-type EGCG dimer) on the preformed bovine insulin amyloid fibrils were studied by several biophysical methods including thioflavin-T (ThT) fluorescence assay , 1-anilinonaphthalene-8-sulfonic (ANS) fluorescence assay, Congo red (CR) binding assay, dynamic light scattering (DLS), transmission electron microscopy (TEM), Gel electrophoresis (SDS-PAGE) and Bradford assay. Our results demonstrated that A-type EGCG dimer showed significantly more potential disaggregative effects on the bovine insulin amyloid fibrils than EGCG. A-type EGCG dimer could not only dramatically promote the disaggregation of the preformed bovine insulin amyloid fibrils, but also restructure the amyloid fibrils into amorphous aggregates. While, EGCG could only shorten and thin the fibrils, but induce no small amorphous aggregates. Our present results provided additional evidence for the more potent disaggregation effects of dimeric polyphenols than monomeric polyphenols and suggested that A-type EGCG dimer seems to have potential application as an excellent anti-amyloidogenic agent.
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