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

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 center dot 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(+)center dot(2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonicacid radical) scavenging and reducing Cu2+, and had higher center dot O-2(-) and DPPH center dot (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 pi-pi conjugative system. The glycosidation of the 3-OH in myricitrin is assumed to sterically hinder atom transfer in the center dot O-2(-) and DPPH center dot 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.