Abstract

The objective was to investigate the therapeutic effects and possible mechanism of sugiol on cerebral ischemia/reperfusion injury (CIRI). The middle cerebral artery occlusion (MCAO) model of rats and oxygen-glucose deprivation (OGD) model were established. To investigate the effects of sugiol on CIRI, neurological score assessment, H&E staining, Nissl staining, TUNEL staining, western blot, RT-qPCR, DCFH-DA staining, CCK-8, and flow cytometry were performed. Network pharmacology analysis was performed for exploring the underlying protective mechanism of sugiol against CIRI. Sugiol exhibited a protective effect against CIRI, as evidenced by reducing histopathological damage, cell apoptosis, improving neurological function, promoting the expression of Bcl-2, inhibiting the expression of Bax, C-caspase-3, TNF-α, IL-1β, MCP-1, decreasing the levels of ROS, MDA, Fe 2+ , and enhancing SOD levels. In vitro, sugiol improved cell viability and inhibited cell apoptosis, inflammation, oxidative stress, and ferroptosis‑associated changes. In vivo and in vitro, sugiol inhibited LRRK2 and p-P65 expression. Notably, the inhibition of sugiol on cell apoptosis, inflammation, oxidative stress, and ferroptosis‑associated changes was reversed by LRRK2 overexpression. In the early phase following MCAO, sugiol alleviated CIRI through the inhibition of cell apoptosis, inflammation, oxidative stress, and ferroptosis‑associated changes, an effect that involves LRRK2/NF-κB pathway.