2. Academic Validation
  3. Daucosterol confers protection against T-2 toxin induced blood-brain barrier toxicity through the PGC-1α-mediated defensive response in vitro and in vivo

Daucosterol confers protection against T-2 toxin induced blood-brain barrier toxicity through the PGC-1α-mediated defensive response in vitro and in vivo

  • J Hazard Mater. 2023 Oct 5;459:132262. doi: 10.1016/j.jhazmat.2023.132262.
Pu Guo 1,  Qirong Lu 1,  Siyi Hu 2,  Yaqin Yang 2,  Xinru Wang 3,  Xinzhou Yang 4,  Xu Wang 5
Affiliations

Affiliations

  • 1 National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China.
  • 2 National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 3 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 4 School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, Hubei 430070, China. Electronic address: xzyang@mail.scuec.edu.cn.
  • 5 National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: wangxu@mail.hzau.edu.cn.
PMID: 37604032 DOI: 10.1016/j.jhazmat.2023.132262
Abstract

T-2 toxin is a common environmental pollutant and contaminant in food and animal feed that represents a great challenge to human and animal' health throughout the world. Using natural compounds to prevent the detrimental effects of T-2 toxin represents an attractive strategy. Peroxisome Proliferator-activated Receptor gamma coactivator 1-alpha (PGC-1α) is a critical regulator in various cellular processes. Recently, PGC-1α activation has been reported to confer protection against neurological injuries. We aimed to identify a potent PGC-1α Activator from Plants as a chemopreventive compound and to demonstrate the efficacy of the compound in attenuating T-2 toxin-induced blood-brain barrier (BBB) toxicity. We identified daucosterol, which binds directly to the 71-74 (-1100 to -1000 bp) position of the second promoter of human PGC-1α by hydrogen bonding. An in vitro and in vivo T-2 toxin induced BBB injury model revealed that this compound can protect against this injury by increasing transepithelial/transendothelial electrical resistance, reducing sodium fluorescein (NaF) infiltration and increasing the expression of tight junction-related proteins (zonula occludens-1 (ZO-1), occludin (OCLN), claudin-5 (CLDN5)) expression. In conclusion, we identified daucosterol as representing a novel of PGC-1α activators and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated the feasibility of using natural compounds targeting PGC-1α as a therapeutic approach to protect humans from environmental insults that may occur daily such as lipopolysaccharide.

Keywords

Agonist; BBB; Daucosterol; PGC-1α; T-2 toxin.

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