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

Pu Guo; Qirong Lu; Siyi Hu; Yaqin Yang; Xinru Wang; Xinzhou Yang; Xu Wang

doi:10.1016/j.jhazmat.2023.132262

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. Epub 2023 Aug 9.

Authors

Pu Guo¹, Qirong Lu¹, Siyi Hu², Yaqin Yang², Xinru Wang³, Xinzhou Yang⁴, Xu Wang⁵

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Blood-Brain Barrier
Humans
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
T-2 Toxin*

Substances

lyoniside
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
T-2 Toxin