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

• Main Authors: Xican Li (Author), Jingyuan Zeng (Author), Yangping Liu (Author), Minshi Liang (Author), Qianru Liu (Author), Zhen Li (Author), Xiaojun Zhao (Author), Dongfeng Chen (Author)
• Format: Book
• Published: MDPI AG, 2020-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

In this study, the anti-ferroptosis effects of catecholic flavonol quercetin and its metabolite quercetin Diels-Alder a<i>nti</i>-dimer (QDAD) were studied using an erastin-treated bone marrow-derived mesenchymal stem cell (bmMSCs) model. Quercetin exhibited higher anti-ferroptosis levels than QDAD, as indicated by 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-undecanoic acid (C11-BODIPY), 2′,7′-dichlorodihydrofluoroscein diacetate (H2DCFDA), lactate dehydrogenase (LDH) release, cell counting kit-8 (CCK-8), and flow cytometric assays. To understand the possible pathways involved, the reaction product of quercetin with the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH^●<b>) </b>was measured using ultra-performance liquid-chromatography coupled with electrospray-ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS). Quercetin was found to produce the same clusters of molecular ion peaks and fragments as standard QDAD. Furthermore, the antioxidant effects of quercetin and QDAD were compared by determining their 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical-scavenging, Cu²⁺-reducing, Fe³⁺-reducing, lipid peroxidation-scavenging, and DPPH^●-scavenging activities. Quercetin consistently showed lower IC₅₀ values than QDAD. These findings indicate that quercetin and QDAD can protect bmMSCs from erastin-induced ferroptosis, possibly through the antioxidant pathway. The antioxidant pathway can convert quercetin into QDAD—an inferior ferroptosis-inhibitor and antioxidant. The weakening has highlighted a rule for predicting the relative anti-ferroptosis and antioxidant effects of catecholic flavonols and their Diels-Alder dimer metabolites.

Item Description

2076-3921
10.3390/antiox9030205