Pomelo Peel Essential Oil Ameliorates Cerebral Ischemia-Reperfusion Injury through Regulating Redox Homeostasis in Rats and SH-SY5Y Cells

Background: In cardiac accident/cardiopulmonary resuscitation (CA/CPR) rat model, oxidative stress occurs during cerebral ischemia/reperfusion injury (CIRI), and antioxidative treatment has a neuroprotective effect. The antioxidant capabilities of pomelo peel essential oil (PPEO) have mostly been investigated in vitro, with little convincing data in vivo, particularly whether PPEO has a neuroprotective role against CIRI.

Methods: In this investigation, a CA/CPR SD rat model and an oxygen-glucose deprivation/reperfusion (OGD/R) SH-SY5Y cell model were used to imitate the CIRI, and the neuroprotective role of PPEO was discovered in both. The morphological changes of neurons after PPEO treatment were observed using Nissl staining and transmission electron microscopy, while biochemical markers such as MDA, GSH, and Fe²⁺ were evaluated. Furthermore, western blot, immunofluorescence, and immunohistochemistry were used to examine the proteins GPX4, SLC7A11, ACSL4, and Nrf2.

Results: Significant morphological alterations were identified during the pathological progression of CIRI. The neurologic deficit scores improved after PPEO therapy, and the expression of GPX4 and SLC7A11 increased, while the levels of intracellular Fe²⁺, ROS, and ACSL4 declined. PPEO also prevented CIRI caused by erastin (a specific inhibitor of SLC7A11) or RSL3 (inhibitor of GPX4). Furthermore, PPEO-induced increases in SLC7A11 and GPX4 may be related to Nrf2 translocation to the nucleus.

Conclusions: In vitro and in vivo, we verified and investigated the neuroprotective effects of PPEO on CIRI. The underlying process may be connected to redox homeostasis regulation, which enhances antioxidative capacity through upmodulation of SLC7A11 and GPX4. It implies that PPEO will be considered as a source of potential adjuvant therapeutic agents for improving CIRI outcomes.