6-Gingerol attenuates subarachnoid hemorrhage-induced early brain injury via GBP2/PI3K/AKT pathway in the rat model

Abstract

Numerous studies have elucidated the neuroprotective effect of 6-gingerol in central nervous system diseases. However, the potential role and mechanism of 6-gingerol on early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains poorly understood. Here, we report that 6-gingerol exerts a neuroprotective effect on SAH-induced EBI through the GBP2/PI3K/AKT pathway. A SAH rat model was established by injecting femoral artery blood into the cisterna magna. 6-gingerol or vehicle was injected intraperitoneally 1 hour post-SAH induction. We found that the neurological function score and brain edema of SAH rats were significantly improved after 6-gingerol treatment, as well as neuronal apoptosis was attenuated in SAH rats by Nissl staining assay and TUNEL assay. To further explore potential molecular mechanisms associated with 6-gingerol, RNA sequencing was implemented to investigate the differences in transcriptomes between SAH rats with and without 6-gingerol treatment; and found that the expression of guanylate-binding protein 2 (GBP2) evidently was suppressed with 6-gingerol treatment compared to vehicle group. In addition, dual immunofluorescence was also employed to investigate changes in neurons, astrocytes, and microglia after 6-gingerol treatment. The results showed that GBP2 was expressed in neurons but not astrocytes or microglia. Western blotting analysis results demonstrated that the PI3K/AKT pathway was activated in the SAH rats treated with 6-gingerol. Furthermore, recombinant GBP2 protein and LY294002 (PI3K inhibitor) treatment reversed the effects of 6-gingerol treatment in SAH rats. These results indicate that 6-gingerol suppressed the expression of GBP2 to activate the PI3K/AKT pathway, improve neurologic outcomes, reduce brain edema and neuronal apoptosis. In summary, our findings suggest that 6-gingerol could attenuate EBI post-SAH in rats, and 6-gingerol may serve as a novel candidate neuroprotective drug for SAH-induced EBI.

Integrated inflammatory signaling landscape response after delivering Elovanoid free-fatty-acid precursors leading to experimental stroke neuroprotection

“…Reduced expression of Gbp2 modulated by C-34:6 may indicate pro-survival and anti-apoptotic mechanistic targets. Gbp2 protein levels increase after brain injury, and overexpression in neuronal cell types has been shown to aggravate neuronal apoptosis 36 . Additionally, decreased expression of C1qC was observed, which is involved in complement cascade activation.…”

Overexpression of Heme oxygenase 1 enhances the neuroprotective effects of exosomes in subarachnoid hemorrhage by suppressing oxidative stress and endoplasmic reticulum stress

“…We performed TUNEL experiments as previously described [19]. Apoptosis Detection Kit (Roche, United States) was used according to the manufacture's instruction.…”

The Critical Role of Sirt1 in Subarachnoid Hemorrhages: Mechanism and Therapeutic Considerations

“…Akt (also known as protein kinase B) is a key antiapoptotic signaling downstream of phosphoinositide 3-kinase (PI3K) that participates in a broad range of cellular processes. Mounting evidence has indicated that the activation of the Akt signaling pathway significantly improved neurological and cognitive functional outcomes [ 106 ] and contributed to the reduction in EBI and neuronal apoptosis after a SAH [ 107 ]. It is well established that Sirt1 interacts with Akt [ 108 ].…”