Psoralidin protects against cerebral hypoxia/reoxygenation injury: Role of GAS6/Axl signaling

Abstract

Psoralidin (PSO) is a natural phenolic coumarin extracted from the seeds of Psoralea corylifolia L. Growing preclinical evidence indicates that PSO has anti‐inflammatory, anti‐vitiligo, anti‐bacterial, and anti‐viral effects. Growth arrest‐specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia/reoxygenation (HR) injury via activating the GAS6/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor‐related factor 2 (Nrf‐2), NAD(P)H dehydrogenase quinone‐1 (NQO1), heme oxygenase‐1 (HO‐1), silent information regulator 1 (SIRT1), peroxisome proliferator‐activated receptor coactivator 1α (PGC‐1α), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B‐cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR‐induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6/Axl signaling.

Revealing the expression characteristics and potential regulatory mechanisms of hub oxidative stress related genes of spinal cord injury

“…However, the role of the Hbegf-Erbb4 and Hbegf-Egfr ligand-receptor pairs in oxidative stress following SCI remains unexplored. Studies have also shown that activation of the GAS6/Axl-AMPK signaling pathway can protect against H2O2-induced oxidative stress, improving oxidative stress, cell apoptosis, and mitochondrial function [33,34] . Therefore, the GAS signaling pathway and the associated ligand-receptor pair Gas-Axl, which mediate cell communication in this study, may have a regulatory role in mitigating oxidative stress post-SCI.…”

Ethyl pyruvate attenuates cerebral hypoxia/reoxygenation injury in neuroblastoma cells: Role of GAS6/Axl signaling

“…LDH release in the culture medium was determined using a commercially available kit according to the manufacturer's protocol (Nanjing Jiancheng Bioengineering Institute). For measurement of ROS production (Beyotime Biotechnology, Shanghai, China), please refer to Lei et al [ 25 ].…”

Activation of ITLN‐1 attenuates oxidative stress injury via activating SIRT1/PGC1‐α signaling in neuroblastoma cells

“…Protein expression was assessed using western blot analysis following established protocols (Lei et al, 2022). The antibody information used during the operation is shown in Supporting Information: Table S1.…”