Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-Butin
<b> </b>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 (<i>S</i>)-butin. C11-BODIPY staining and flow cytometric...
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MDPI AG
2020-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/3/674 |
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| author | Jie Liu Xican Li Rongxin Cai Ziwei Ren Aizhen Zhang Fangdan Deng Dongfeng Chen |
| author_facet | Jie Liu Xican Li Rongxin Cai Ziwei Ren Aizhen Zhang Fangdan Deng Dongfeng Chen |
| author_sort | Jie Liu |
| collection | DOAJ |
| description | <b> </b>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 (<i>S</i>)-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 (<i>S</i>)-butin. Butein also exhibited higher antioxidant percentages than (<i>S</i>)-butin in five antioxidant assays: linoleic acid emulsion assay, Fe<sup>3+</sup>-reducing antioxidant power assay, Cu<sup>2+</sup>-reducing antioxidant power assay, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO<sup>•</sup>)-trapping assay, and α,α-diphenyl-β-picrylhydrazyl radical (DPPH<sup>•</sup>)-trapping assay. Their reaction products with DPPH<sup>•</sup> 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 (<i>S</i>)-butin produced a butein 5,5-dimer (<i>m/z</i> 542, 271, 253, 225, 135, and 91) and a (<i>S</i>)-butin 5′,5′-dimer (<i>m/z</i> 542, 389, 269, 253, and 151), respectively. Interestingly, butein forms a cross dimer with (<i>S</i>)-butin (<i>m/z</i> 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. |
| first_indexed | 2024-04-12T08:18:50Z |
| format | Article |
| id | doaj.art-6d8af06c0b4f487dbfe6ec71191f6ffa |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T08:18:50Z |
| publishDate | 2020-02-01 |
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| series | Molecules |
| spelling | doaj.art-6d8af06c0b4f487dbfe6ec71191f6ffa2022-12-22T03:40:40ZengMDPI AGMolecules1420-30492020-02-0125367410.3390/molecules25030674molecules25030674Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-ButinJie Liu0Xican Li1Rongxin Cai2Ziwei Ren3Aizhen Zhang4Fangdan Deng5Dongfeng Chen6School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, ChinaSchool of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, ChinaSchool of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, ChinaSchool of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, ChinaSchool of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, ChinaSchool of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China<b> </b>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 (<i>S</i>)-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 (<i>S</i>)-butin. Butein also exhibited higher antioxidant percentages than (<i>S</i>)-butin in five antioxidant assays: linoleic acid emulsion assay, Fe<sup>3+</sup>-reducing antioxidant power assay, Cu<sup>2+</sup>-reducing antioxidant power assay, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO<sup>•</sup>)-trapping assay, and α,α-diphenyl-β-picrylhydrazyl radical (DPPH<sup>•</sup>)-trapping assay. Their reaction products with DPPH<sup>•</sup> 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 (<i>S</i>)-butin produced a butein 5,5-dimer (<i>m/z</i> 542, 271, 253, 225, 135, and 91) and a (<i>S</i>)-butin 5′,5′-dimer (<i>m/z</i> 542, 389, 269, 253, and 151), respectively. Interestingly, butein forms a cross dimer with (<i>S</i>)-butin (<i>m/z</i> 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.https://www.mdpi.com/1420-3049/25/3/674butein(s)-butinanti-ferroptosisantioxidant2′-hydroxy chalconeisomerization |
| spellingShingle | Jie Liu Xican Li Rongxin Cai Ziwei Ren Aizhen Zhang Fangdan Deng Dongfeng Chen Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-Butin Molecules butein (s)-butin anti-ferroptosis antioxidant 2′-hydroxy chalcone isomerization |
| title | Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-Butin |
| title_full | Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-Butin |
| title_fullStr | Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-Butin |
| title_full_unstemmed | Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-Butin |
| title_short | Simultaneous Study of Anti-Ferroptosis and Antioxidant Mechanisms of Butein and (<i>S</i>)-Butin |
| title_sort | simultaneous study of anti ferroptosis and antioxidant mechanisms of butein and i s i butin |
| topic | butein (s)-butin anti-ferroptosis antioxidant 2′-hydroxy chalcone isomerization |
| url | https://www.mdpi.com/1420-3049/25/3/674 |
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