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
  • [41] Curcumin induces stabilization of Nrf2 protein through Keap1 cysteine modification
    Shin, Jun Wan
    Chun, Kyung-Soo
    Kim, Do-Hee
    Kim, Su-Jung
    Kim, Seong Hoon
    Cho, Nam-Chul
    Na, Hye-Kyung
    Surh, Young-Joon
    BIOCHEMICAL PHARMACOLOGY, 2020, 173
  • [42] Zearalenone induces oxidative damage involving Keap1/Nrf2/HO-1 pathway in hepatic L02 cells
    Wu, Kejia
    Liu, Xin
    Fang, Min
    Wu, Yongning
    Gong, Zhiyong
    MOLECULAR & CELLULAR TOXICOLOGY, 2014, 10 (04) : 451 - 457
  • [43] Sestrins Activate Nrf2 by Promoting p62-Dependent Autophagic Degradation of Keap1 and Prevent Oxidative Liver Damage
    Bae, Soo Han
    Sung, Su Haeng
    Oh, Sue Young
    Lim, Jung Mi
    Lee, Se Kyoung
    Park, Young Nyun
    Lee, Hye Eun
    Kang, Dongmin
    Rhee, Sue Goo
    CELL METABOLISM, 2013, 17 (01) : 73 - 84
  • [44] NRF2 pathway activation by KEAP1 inhibition attenuates the manifestation of aging phenotypes in salivary glands
    Wati, Sisca Meida
    Matsumaru, Daisuke
    Motohashi, Hozumi
    REDOX BIOLOGY, 2020, 36
  • [45] Inhibition of the Keap1/Nrf2 Signaling Pathway Significantly Promotes the Progression of Type 1 Diabetes Mellitus
    Lou, Yanmei
    Kong, Muyan
    Li, Leyan
    Hu, Yu
    Zhai, Wenjun
    Qi, Xiaoxiao
    Liu, Zhongqiu
    Wu, Jinjun
    OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2021, 2021
  • [46] p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells
    Xia, Mei-hui
    Yan, Xiao-yu
    Zhou, Lei
    Xu, Long
    Zhang, Li-chao
    Yi, Hao-wei
    Su, Jing
    JOURNAL OF CANCER, 2020, 11 (06): : 1299 - 1307
  • [47] Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis
    Tossetta, Giovanni
    Fantone, Sonia
    Togni, Lucrezia
    Santarelli, Andrea
    Olivieri, Fabiola
    Marzioni, Daniela
    Rippo, Maria Rita
    ANTIOXIDANTS, 2024, 13 (10)
  • [48] Structure of the Keap1: Nrf2 interface provides mechanistic insight into Nrf2 signaling
    Lo, Shih-Ching
    Li, Xuchu
    Henzl, Michael T.
    Beamer, Lesa J.
    Hannink, Mark
    EMBO JOURNAL, 2006, 25 (15): : 3605 - 3617
  • [49] Antifibrotic potential of reserpine (alkaloid) targeting Keap1/Nrf2; oxidative stress pathway in CCl4-induced liver fibrosis
    Sohail, Aamir
    Shams, Faiza
    Nawaz, Aleeza
    ul Ain, Qurrat
    Ijaz, Bushra
    CHEMICO-BIOLOGICAL INTERACTIONS, 2025, 407
  • [50] Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway
    Hassanein, Emad H. M.
    Sayed, Ahmed M.
    Hussein, Omnia E.
    Mahmoud, Ayman M.
    OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2020, 2020