Effect and molecular mechanism of Sulforaphane alleviates brain damage caused by acute carbon monoxide poisoning:Network pharmacology analysis, molecular docking, and experimental evidence.

Autor: Yue AC; Emergency Department, Shenzhen University General Hospital, Shenzhen, People's Republic of China.; Centre of Integrated Chinese and Western Medicine, School of Clinical Medicine, Qingdao University, Qingdao, People's Republic of China., Zhou XD; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China., Song HP; First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China., Liu XH; Emergency Department, Shenzhen University General Hospital, Shenzhen, People's Republic of China., Bi MJ; Physical Examination Centre, Yuhuangding Hospital Affiliated to Qingdao University, Yantai, People's Republic of China., Han W; Emergency Department, Shenzhen University General Hospital, Shenzhen, People's Republic of China., Li Q; Emergency Department, Shenzhen University General Hospital, Shenzhen, People's Republic of China.
Jazyk: angličtina
Zdroj: Environmental toxicology [Environ Toxicol] 2024 Mar; Vol. 39 (3), pp. 1140-1162. Date of Electronic Publication: 2023 Oct 20.
DOI: 10.1002/tox.24000
Abstrakt: Sulforaphane (SFN) has attracted much attention due to its ability on antioxidant, anti-inflammatory, and anti-apoptotic properties, while its functional targets and underlying mechanism of action on brain injury caused by acute carbon monoxide poisoning (ACOP) have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the mechanism of SFN in the treatment of brain damage after ACOP. In this study, the results of network pharmacology demonstrated that there were a total of 81 effective target genes of SFN and 36 drug-disease targets, which were strongly in connection with autophagy-animal signaling pathway, drug metabolism, and transcription disorders in cancer. Upon the further biological function and KEGG signaling pathway enrichment analysis, a large number of them were involved in neuronal death, reactive oxygen metabolic processes and immune functions. Moreover, based on the results of bioinformatics prediction associated with multiple potential targets and pathways, the AMP-activated protein kinase (AMPK) signaling pathway was selected to elucidate the molecular mechanism of SFN in the treatment of brain injury caused by ACOP. The following molecular docking analysis also confirmed that SFN can bind to AMPKα well through chemical bonds. In addition, an animal model of ACOP was established by exposure to carbon monoxide in a hyperbaric oxygen chamber to verify the predicted results of network pharmacology. We found that the mitochondrial ultrastructure of neurons in rats with ACOP was seriously damaged, and apoptotic cells increased significantly. The histopathological changes were obviously alleviated, apoptosis of cortical neurons was inhibited, and the number of Nissl bodies was increased in the SFN group as compared with the ACOP group (p < .05). Besides, the administration of SFN could increase the expressions of phosphorylated P-AMPK and MFN2 proteins and decrease the levels of DRP1, Caspase3, and Casapase9 proteins in the brain tissue of ACOP rats. These findings suggest that network pharmacology is a useful tool for traditional Chinese medicine (TCM) research, SFN can effectively inhibit apoptosis, protect cortical neurons from the toxicity of carbon monoxide through activating the AMPK pathway and may become a potential therapeutic strategy for brain injury after ACOP.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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