Network pharmacology and in vivo experimental studies reveal the protective effects of 6-hydroxygenistein against hypobaric hypoxia-induced brain injury

Hypobaric hypoxia-induced brain injury (HHBI) is a progressive neurodegenerative disease that has still not been effectively treated. There are several different mechanisms involved in HHBI. Among them, oxidative stress and inflammation response predominate. 6-hydroxygenistein (4',5,6,7-tetrahydroxyisoflavone, 6-OHG) is a hydroxylated derivative of genistein with excellent antioxidant activity, however, the protective effects and underlying mechanisms against HHBI have not been clarified. In the present study, we aimed to explore the mechanisms of action of 6-OHG on HHBI using network pharmacology and experimental validation. Network pharmacology analysis revealed 186 candidate targets through the intersection of the targets of 6-OHG and related genes in HHBI, which were mainly enriched in oxidative stress and inflammation response. Moreover, key targets of 6-OHG against HHBI, namely Nrf2 and NF-κB, were screened and found to be closely related to oxidative stress and inflammation response. Subsequent