Morin Reactivates Nrf2 by Targeting Inhibition of Keap1 to Alleviate Deoxynivalenol-Induced Intestinal Oxidative Damage

被引:1
|
作者
Zan, Gengxiu [1 ]
He, Hui [1 ]
Wang, Xiaofan [1 ]
Zhou, Jiayi [1 ]
Wang, Xiuqi [1 ]
Yan, Huichao [1 ]
机构
[1] South China Agr Univ, Coll Anim Sci, Natl Engn Res Ctr Breeding Swine Ind, State Key Lab Swine & Poultry Breeding Ind,Guangdo, Guangzhou 510642, Peoples R China
基金
中国国家自然科学基金;
关键词
deoxynivalenol; Morin; intestinal stem cells; oxidative stress; Keap1/Nrf2 signaling pathway; HO-1; EXPRESSION; STRESS; ANTIOXIDANT; INDUCTION;
D O I
10.3390/ijms26031086
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
As a prevalent mycotoxin found in cereal foods and feed, deoxynivalenol (DON) disrupts the orderly regeneration of intestinal epithelial tissue by interfering with the intracellular antioxidant defense system. However, the potential of mulberry leaf-derived Morin, a natural flavonoid active substance with clearing reactive oxygen species (ROS), to mitigate DON-induced intestinal oxidative damage remains unclear. Our investigation demonstrates that Morin effectively reverses the decline in growth performance and repairs damaged jejunal structures and barrier function under DON exposure. Furthermore, the proliferation and differentiation of intestinal stem cells (ISCs) is enhanced significantly after Morin intervention. Importantly, Morin increases the levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the serum and jejunal tissue, while reducing the accumulation of ROS and malondialdehyde (MDA). Molecular interaction analysis further confirms that Morin targets inhibition of Keap1 to activate the Nrf2-mediated antioxidant system. In summary, our results suggest that Morin alleviates the oxidative damage induced by DON by regulating the Keap1/Nrf2 pathway, thereby restoring the proliferation and differentiation activity of ISC, which provides new insights into Morin mitigating DON damage.
引用
收藏
页数:13
相关论文
共 50 条
  • [21] Electrophilic targeting of Keap1/Nrf2 signalling for disease prevention and treatment
    Dinkova-Kostova, Albena
    Honda, Tadashi
    Abramov, Andrey
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2018, 256
  • [22] Targeting the Keap1/Nrf2/ARE pathway and the heat shock response for chemoprotection
    Dinkova-Kostova, Albena T.
    Honda, Tadashi
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2012, 244
  • [23] Protective mechanism against oxidative stress by Keap1/Nrf2 pathway
    Itoh, K
    SEIKAGAKU, 2006, 78 (02): : 79 - 92
  • [24] Tea polyphenols alleviate hydrogen peroxide-induced oxidative stress damage through the Mst/Nrf2 axis and the Keap1/Nrf2/HO-1 pathway in murine RAW264.7 cells
    Li, Qian
    Qiu, Zhaoyan
    Wang, Yan
    Guo, Chunyan
    Cai, Xu
    Zhang, Yandong
    Liu, Li
    Xue, Hongkun
    Tang, Jintian
    EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2021, 22 (06)
  • [25] Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals
    Bhattacharjee, Shamee
    Dashwood, Roderick H.
    ANTIOXIDANTS, 2020, 9 (09) : 1 - 22
  • [26] Mechanism of the Nrf2/Keap1/ARE signaling system
    V. O. Tkachev
    E. B. Menshchikova
    N. K. Zenkov
    Biochemistry (Moscow), 2011, 76 : 407 - 422
  • [27] Mechanism of the Nrf2/Keap1/ARE signaling system
    Tkachev, V. O.
    Menshchikova, E. B.
    Zenkov, N. K.
    BIOCHEMISTRY-MOSCOW, 2011, 76 (04) : 407 - 422
  • [28] The cytoprotective role of the Keap1–Nrf2 pathway
    Liam Baird
    Albena T. Dinkova-Kostova
    Archives of Toxicology, 2011, 85 : 241 - 272
  • [29] Beyond repression of Nrf2: An update on Keap1
    Kopacz, Aleksandra
    Kloska, Damian
    Forman, Henry Jay
    Jozkowicz, Alicja
    Grochot-Przeczek, Anna
    FREE RADICAL BIOLOGY AND MEDICINE, 2020, 157 : 63 - 74
  • [30] The KEAP1/NRF2 Signaling Pathway in Keratinization
    Ishitsuka, Yosuke
    Ogawa, Tatsuya
    Roop, Dennis
    ANTIOXIDANTS, 2020, 9 (08) : 1 - 24