Structure-Dependent Membrane-Perturbing Potency of Four Proanthocyanidin Dimers on 3T3-L1 Preadipocytes.

Proanthocyanidins (PAs) have been widely recognized for their broad spectrum of beneficial health effects, which are highly structure-dependent. It was found that PA dimers epicatechin-3-gallate-(4β→8,2β→O→7)-epicatechin-3-gallate (A-type ECG dimer) and epigallocatechin-3-gallate-(4β→,2β→O→7)-epigallocatechin-3-gallate (A-type EGCG dimer) inhibit the differentiation of 3T3-L1 cells significantly, whereas epicatechin-(4β→8,2β→O→7)-epicatechin (A-type EC dimer) and epicatechin-(4β→8)-epicatechin (B-type EC dimer) showed little effect in previous work. However, the underlying mechanisms are unclear. To test whether bilayer perturbation may underlie this diversity of actions, we examined the bilayer-modifying effects of the four dimers in both 3T3-L1 cell and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine liposome models by using scanning electron microscopy, fluorescent spectroscopy, differential scanning calorimetry, and molecular dynamics methods. Our results revealed that A-type ECG and EGCG dimers had a high affinity for the lipid bilayer and could form simultaneous hydrogen bonds (H-bond) with both the surface oxygen acceptors and the deeper inside lipid oxygen atoms. However, A-type and B-type EC dimers contacted only the surface oxygen atoms with limited and significantly fewer H-bonds. A-type ECG and EGCG dimers notably distorted the membrane morphology of 3T3-L1 cells. In the present study, we found there was a high positive correlation between the membrane-disturbing abilities of the four dimers and their 3T3-L1 cell differentiation inhibitory effects as previously reported. This indicated that the strong 3T3-L1 cell differentiation inhibitory effect of A-type ECG and EGCG dimers might be due to their strong bilayer-perturbing potency.