ginkgetin and Stroke

Neuroinflammation plays an important role in the pathophysiological process of acute cerebral infarction, which may aggravate brain injury and hinder neuro-repair. Microglia are innate immune cells in the brain. Ginkgetin has anti-inflammatory and neuroprotective effects, but the mechanism remains unclear. This study aims to explore the regulatory effects of ginkgetin on microglia polarization in brain ischemia. Oxygen glucose deprivation (OGD) cellular model and middle cerebral artery occlusion (MCAO) animal model was used in this study. We first observed the dynamic process of microglia polarization in ischemic stroke, and then investigated the effect of ginkgetin treatment on microglia polarization. Finally, we studied the role of PPARγ signaling pathway and the blocking effect of PPARγ antagonist GW9662 in this process. OGD and cerebral ischemia polarized microglia mainly to M1 type. However, ginkgetin treatment converted microglia from M1 type to M2 type, inhibited neuroinflammation, and exerted neuronal protective effects. PPARγ signaling pathway was activated during this process. The above effects could be blocked by GW9662. Ginkgetin can promote M2 polarization of microglia through PPARγ signaling pathway, thereby inhibiting neuroinflammation and promoting recovery of neurological functions in ischemic stroke.

Topics: Anilides; Animals; Biflavonoids; Brain Ischemia; Infarction, Middle Cerebral Artery; Ischemic Stroke; Microglia; Neuroprotection; PPAR gamma; Stroke

The present investigation evaluates the protective effect of Ginkgetin aglycone (GA) against ischemic stroke-induced neuronal injury. Ischemic stroke was produced by the middle cerebral artery occlusion (MCAO) model and animals were a group that received GA 100 and 200 mg/kg, i.p. five days before the induction of MCAO. The effect of GA against stroke was determined by estimating the neurological deficit score and brain water content was also observed. Moreover terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay was done for determining the neuronal apoptosis and Western blot assay also performed for estimating the expression of several proteins. Results of the study suggest that the neurological deficit score and brain water content was found to be lower in the GA treated group than the ischemia/reperfusion (I/R) group of rats. Moreover the number of TUNEL positive cells was found to be lower in the GA treated group than in the I/R group of rats. There was a significant (p < 0.01) decrease in the oxidative stress parameters and cytokine in the tissue homogenate of the GA treated group compared to the I/R group of rats. Further treatment with GA attenuates altered expression of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), protein kinase B (Akt), B-cell lymphoma 2 (Bcl-2), signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa light chain enhancer of activated B cells (NF-B), toll-like receptor 4 (TLR-4), Janus kinase 2 (JAK-2) and sirtuin-1 (SIRT-1) protein in the brain tissues of stroke rats. In conclusion, data of the report reveal that treatment with Ginkgetin aglycone protects the neuronal injury against stroke in rats by reducing oxidative stress and inflammation.

Topics: Animals; Anti-Inflammatory Agents; Biflavonoids; Inflammation; Janus Kinase 2; Male; Neurons; Neuroprotective Agents; Rats; Rats, Wistar; Signal Transduction; Sirtuin 1; STAT3 Transcription Factor; Stroke