1. Academic Validation
  2. Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and ( S)-Butin

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

  • Molecules. 2020 Feb 5;25(3):674. doi: 10.3390/molecules25030674.
Jie Liu 1 2 Xican Li 3 Rongxin Cai 3 Ziwei Ren 3 Aizhen Zhang 3 Fangdan Deng 3 Dongfeng Chen 1 2
Affiliations

Affiliations

  • 1 School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 2 The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
  • 3 School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.
Abstract

To elucidate the mechanism of anti-ferroptosis and examine structural optimization in natural phenolics, cellular and chemical assays were performed with 2'-hydroxy chalcone butein and dihydroflavone (S)-butin. C11-BODIPY staining and flow cytometric assays suggest that butein more effectively inhibits Ferroptosis in erastin-treated bone marrow-derived mesenchymal stem cells than (S)-butin. Butein also exhibited higher antioxidant percentages than (S)-butin in five antioxidant assays: linoleic acid emulsion assay, Fe3+-reducing antioxidant power assay, Cu2+-reducing antioxidant power assay, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO)-trapping assay, and α,α-diphenyl-β-picrylhydrazyl radical (DPPH)-trapping assay. Their reaction products with DPPH were further analyzed using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS). Butein and (S)-butin produced a butein 5,5-dimer (m/z 542, 271, 253, 225, 135, and 91) and a (S)-butin 5',5'-dimer (m/z 542, 389, 269, 253, and 151), respectively. Interestingly, butein forms a cross dimer with (S)-butin (m/z 542, 523, 433, 419, 415, 406, and 375). Therefore, we conclude that butein and (S)-butin exert anti-ferroptotic action via an antioxidant pathway (especially the hydrogen atom transfer pathway). Following this pathway, butein and (S)-butin yield both self-dimers and cross dimers. Butein displays superior antioxidant or anti-ferroptosis action to (S)-butin. This can be attributed the decrease in π-π conjugation in butein due to saturation of its α,β-double bond and loss of its 2'-hydroxy group upon biocatalytical isomerization.

Keywords

(S)-butin; 2′-hydroxy chalcone; anti-ferroptosis; antioxidant; butein; isomerization.

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