Neuroprotective effect and mechanism of daidzein in oxygen-glucose deprivation/reperfusion injury based on experimental approaches and network pharmacology

Background: Daidzein, phytoestrogens derived from the Pueraria lobata (Willd.) Ohwi root used in traditional Chinese medicine, has a wide range of biological activities, including antioxidant, anti-inflammatory, and neuroprotection. However, the neuroprotective role of daidzein in oxygen-glucose deprivation/reperfusion injury and its underlying mechanism are still unknown.Methods: In this study, we used pheochromocytoma cells induced by oxygen-glucose deprivation and reperfusion to study the potential effect in the protection of the nerve cells. Then, we used molecular docking simulation and network pharmacology to predict the possible targets and pharmacological pathways of daidzein. Western blot was used to verify the expression of target proteins with or without adding the inhibitors. Results: After daidzein treatment, cell vitality had an upward trend (P < 0.05) and the release of lactate dehydrogenase had a downward trend (P < 0.01) in dose-dependent compared with the model group by exposure to oxygen-glucose deprivation and reperfusion. Several core targets were analyzed through network pharmacology and molecular docking including catalase, peroxisome proliferator-activated receptor gamma, vascular endothelial growth factor A, interleukin-6, tumor necrosis factor, nitric oxide synthase 3, prostaglandin-endoperoxide synthase 2, and RAC-alpha serine/threonine kinase 1. These results suggest that catalase may be a first-ranked target for the neuroprotective role of daidzein. Gene Ontology enrichment analysis indicated the pathways mainly contained molecule metabolic process, while Kyoto Encyclopedia of Genes and Genomes enrichment analysis focus on pathways in terms of inflammation such as tumor necrosis factor signal pathway. Then, Western blot results showed that daidzein had a significant increase on the expression of protein catalase (P < 0.01). Daidzein reversed catalase level alterations after oxygen-glucose deprivation reperfusion injury in a dose-dependent manner which was consistent with the catalase antagonists-based experiments. Conclusion: These outcomes provide new insights into the neuroprotective effect and mechanism of daidzein in oxygen-glucose deprivation/reperfusion injury.