Gastrodin Injection Relieves Hypoxic-Ischemic Brain Injury in Newborn Rats by Regulating the P62/Nrf2/HO-1 Pathway.

Hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal mortality and disability, yet effective treatments remain limited. Gastrodia elata is a Chinese medicinal herb that has both medicinal and edible properties. Previous studies have shown that gastrodin has neuroprotective potential for brain injury. There is currently no clear evidence proving that gastrodin is toxic to newborns. Gastrodin may be a promising drug for treating HIE. To investigate this, a hypoxic-ischemic brain damage (HIBD) model in neonatal rats was established, followed by an immediate intraperitoneal injection of gastrodin injection. The model was validated using laser speckle contrast imaging, and brain tissue damage was assessed using hematoxylin-eosin (H&E) staining, Nissl staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurobehavioral evaluations were conducted and Western blotting and ELISA were used to analyze oxidative stress and inflammatory cytokine levels in brain tissue. Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) injury model was created using SH-SY5Y cells, which were treated with gastrodin injection immediately following the induction of injury. The P62-specific inhibitor XRK3F2 was then used to examine the neuroprotective mechanisms of gastrodin injection in more detail. Cell viability, intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential and oxidative stress-related proteins were then measured. The results showed that gastrodin injection significantly reduced the volume of cerebral infarction in HIBD rats, alleviated oxidative stress-induced neuronal damage and improved short- and long-term neurobehavioral deficits. Gastrodin injection also enhanced mitochondrial function, boosted antioxidant capacity, and attenuated neuroinflammation. In the OGD/R model, gastrodin injection increased neuronal survival, suppressed oxidative stress and inhibited apoptosis. However, these neuroprotective effects were partially reversed by XRK3F2, a P62 inhibitor. This study suggests that gastrodin injection may reduce oxidative stress and apoptosis, thereby improving the outcome of brain injury following HIBD. This study shows that gastrodin injections could improve the outcome for rats with HIBD, possibly by activating the P62/Nrf2/HO-1 pathway; it should be noted that this study neither validated direct interactions between proteins nor employed direct counting for neuronal survival rates. Additionally, the long-term effects on the nervous system were not examined at the protein level. These areas represent directions for future research requiring further refinement.