Bergaptol Alleviates Oxidative Stress and Inflammation in Intracerebral Haemorrhage Mice via JAK2/STAT3 and NF-κB Pathways, Improving Neurological Function

Background: Bergaptol has demonstrated various pharmacological activities, including antitumor, anti-inflammatory and neuroprotective effects. However, its therapeutic potential and underlying mechanisms in intracerebral haemorrhage (ICH) remain elusive.

Methods: ICH mice were treated with a daily intraperitoneal injection of bergaptol (20 or 40 mg/kg) for five consecutive days. Neurological function was assessed using the Garcia score; brain edema was measured by the wet/dry weight method. The expressions of NeuN and Iba1 were detected by immunofluorescence staining. The levels of oxidative stress markers (SOD, CAT and MDA) and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were measured by ELISA. Furthermore, the phosphorylation levels of JAK2, STAT3 and NF-κB p65 were determined by Western blotting. The Morris Water Maze (MWM) test was conducted to assess long-term neurological function, and hippocampal neuronal dendritic spines were visualized using Golgi-Cox staining.

Results: The results showed that bergaptol dose-dependently improved neurological function, attenuated acute cerebral edema, alleviated the reduction of perihematomal cortical neurons, and prevented the loss of hippocampal neuronal dendritic spines in experimental ICH. Mechanistically, bergaptol alleviated oxidative stress and inflammation, potentially by inhibiting the JAK2/STAT3 and NF-κB signaling pathways.

Conclusions: Bergaptol attenuated oxidative stress and inflammation while improving neurological function in a mouse model of ICH, potentially through modulation of the JAK2/STAT3 and NF-κB signaling pathways.

bergaptol; inflammation; intracerebral haemorrhage; neuroprotection and brain edema; oxidative stress.