Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice

In this study, 428 adult male C57BL/6J mice weighing 20 to 25 g were observed to investigate the effects of Bak administration in an SAH animal model. The neurological function and brain edema were assessed. Content of MDA/3-NT/8-OHdG/superoxide anion and the activity of SOD and GSH-Px were tested. The function of the blood-brain barrier (BBB) and the protein levels of claudin-5, occludin, zonula occludens-1, and matrix metalloproteinase-9 were observed. TUNEL staining and Fluoro-Jade C staining were conducted to evaluate the death of neurons. Ultrastructural changes of the neurons were observed under the transmission electron microscope. Finally, the roles of Trx, TXNIP, and AMPK in the protective effect of Bak were investigated. The data showed that Bak administration 1) increased the survival rate and alleviated neurological functional deficits; 2) alleviated BBB disruption and brain edema; 3) attenuated oxidative stress by reducing reactive oxygen species, MDA, 3-NT, 8-OHdG, gp91phox, and 4-HNE; increased the activities of SOD and GSH-Px; and alleviated the damage to the ultrastructure of mitochondria; 4) inhibited cellular apoptosis by regulating the protein levels of Bcl-2, Bax, and cleaved caspase-3; and 5) upregulated the protein levels of Trx1 as well as the phosphorylation of AMPK and downregulated the protein levels of TXNIP. Moreover, the protective effects of Bak were partially reversed by PX-12 and compound C. To summarize, Bak attenuates EBI after SAH by allevi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research