Comparative Analysis of Radical Adduct Formation (RAF) Products and Antioxidant Pathways between Myricetin-3-O-Galactoside and Myricetin Aglycone

Abstract

The biological process, 3-O-galactosylation, is important in plant cells. To understand the mechanism of the reduction of flavonol antioxidative activity by 3-O-galactosylation, myricetin-3-O-galactoside (M3OGa) and myricetin aglycone were each incubated with 2 mol α,α-diphenyl-β-picrylhydrazyl radical (DPPH•) and subsequently comparatively analyzed for radical adduct formation (RAF) products using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS) technology. The analyses revealed that M3OGa afforded an M3OGa–DPPH adduct (m/z 873.1573) and an M3OGa–M3OGa dimer (m/z 958.1620). Similarly, myricetin yielded a myricetin–DPPH adduct (m/z 711.1039) and a myricetin–myricetin dimer (m/z 634.0544). Subsequently, M3OGa and myricetin were compared using three redox-dependent antioxidant analyses, including DPPH•-trapping analysis, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-trapping analysis, and •O2 inhibition analysis. In the three analyses, M3OGa always possessed higher IC50 values than those of myricetin. Conclusively, M3OGa and its myricetin aglycone could trap the free radical via a chain reaction comprising of a propagation step and a termination step. At the propagation step, both M3OGa and myricetin could trap radicals through redox-dependent antioxidant pathways. The 3-O-galactosylation process, however, could limit these pathways; thus, M3OGa is an inferior antioxidant compared to its myricetin aglycone. Nevertheless, 3-O-galactosylation has a negligible effect on the termination step. This 3-O-galactosylation effect has provided novel evidence that the difference in the antioxidative activities of phytophenols exists at the propagation step rather than the termination step.

Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (S)-Butin

“…Its dimer was hypothesized to form via a 5 ,5 -linkage. This (S)-butin 5 ,5 -dimer tended to undergo retro-Diels-Alder fragmenting during MS, similar to other flavonoid dimers [63,73]. As a result, the (S)-butin 5 ,5 -dimer generated characteristic MS peaks, such as m/z 389, 269, 253, and 151 ( Figure 6).…”

Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin)

“…The activities of piceatannol and astringin for superoxide anion radical ( • O 2 − ) scavenging suggest that they likely mediate ROS scavenging, a conventional antioxidant mechanism, to inhibit ferroptosis. This proposal is further supported by the following three facts: (1) Ferroptosis is closely associated with extensive ROS (including LPO) production [ 21 , 27 , 28 , 29 ]; (2) the relative ferroptosis-inhibitory levels correlate with the relative antioxidant levels of piceatannol and astringin ( Table 1 and Figure 2 ); however, the antioxidant difference between the two stilbenes can be attributed to 3-OH glycosylation, according to a previous antioxidant structure–activity relationship analysis [ 30 , 31 ]; and (3) nowadays, many natural phenolic antioxidants have already been proven to be ferroptosis inhibitors, such as corilagin [ 6 ], baicalein [ 32 ], and isorhapontigenin [ 33 ].…”

Inhibitory Effect and Mechanism of Action of Quercetin and Quercetin Diels-Alder anti-Dimer on Erastin-Induced Ferroptosis in Bone Marrow-Derived Mesenchymal Stem Cells

“…In summary, MS elucidation revealed that quercetin interacted with DPPH • to yield its dimer metabolite QDAD. Considering previous studies related to DPPH • hydrogen-abstraction reactions [68,69] and quercetin dimerization reactions [23,[70][71][72], the whole process can be proposed as shown in Figure 8. It should be noted that, firstly, there was no so-called syn dimer because of the hinderance from head-head addition ( Figure 8B).…”