Protective Effects of Dihydromyricetin against •OH-Induced Mesenchymal Stem Cells Damage and Mechanistic Chemistry.

Xican Li,Jian Lin,Dongfeng Chen,Jieyuan Huang,Tingting Wang,Jingjing Liu,Yongqiang Lin

doi:10.3390/molecules21050604

Abstract

As a natural flavonoid in Ampelopsis grossedentata, dihydromyricetin (DHM, 2R,3R-3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol) was observed to increase the viability of •OH-treated mesenchymal stem cells using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl] assay and flow cytometry analysis. This protective effect indicates DHM may be a beneficial agent for cell transplantation therapy. Mechanistic chemistry studies indicated that compared with myricetin, DHM was less effective at ABTS+• (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical) scavenging and reducing Cu2+, and had higher •O2− and DPPH• (1,1-diphenyl-2-picrylhydrazyl radical) scavenging activities. Additionally, DHM could also chelate Fe2+ to give an absorption maximum at 589 nm. Hence, such protective effect of DHM may arise from its antioxidant activities which are thought to occur via direct radical-scavenging and Fe2+-chelation. Direct radical-scavenging involves an electron transfer (ET) pathway. The hydrogenation of the 2,3-double bond is hypothesized to reduce the ET process by blocking the formation of a larger π-π conjugative system. The glycosidation of the 3–OH in myricitrin is assumed to sterically hinder atom transfer in the •O2− and DPPH• radical-scavenging processes. In DHM, the Fe2+-chelating effect can actually be attributed to the 5,3′,4′,5′–OH and 4–C=O groups, and the 3–OH group itself can neither scavenge radicals nor chelate metal.

Highlights

It is well documented that bone marrow-derived mesenchymal stem cell transplantation represents one of the more promising new strategies in the treatment of various diseases such as neuronal regeneration [1,2], brain damage [3,4], liver damage [5], and heart failure [6]
Based on this knowledge and the ABTS+ reaction with the pyrogallol moiety [31,32], we proposed the initial stage of the DHM reaction with the ABTS+ radical cation to occur as shown in
(2,9-dimethyl-1,10-phenanthroline hemihydrate), Trolox [( ̆)-6-hydroxyl-2,5,7,8-tetramethly chroman-2-carboxylic acid], ferrozine [3-(2-pyridyl)-5,6-bis(4-phenylsulfonicacid)-1,2,4-triazine], 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT), and pyrogallol were purchased from Sigma Co

Summary

Introduction

It is well documented that bone marrow-derived mesenchymal stem cell (bmMSC) transplantation represents one of the more promising new strategies in the treatment of various diseases such as neuronal regeneration [1,2], brain damage [3,4], liver damage [5], and heart failure [6]. In the process of transplantation, various reactive oxygen species (ROS) may cause oxidative damage and apoptosis [7]. These ROS mainly include superoxide radical anion (‚O2 ́ ), peroxynitrite (ONOO ), hydroxyl radical (‚OH), and so on. The ‚O2 ́ and ONOOradicals have recently been reported to be inhibited by the antioxidant defense system in bmMSCs to some extent [2,4]. BmMSCs themselves had antioxidant potential to decrease oxidative damage and apoptotic death [5]. Such endogenous antioxidant potential cannot guarantee the cell survival for their clinical applications

Methods

Results

Conclusion