Neuroprotection of boropinol-B in cerebral ischemia-reperfusion injury by inhibiting inflammation and apoptosis

Abstract

Ischemic stroke is the leading cause of death and disability worldwide. The activation of gamma-aminobutyric acid A (GABA_A) receptors can attenuate cerebral ischemia-reperfusion injury (CI/RI). Boropinol-B, originally isolated from Boronia pinnata Sm. (Rutaceae), has been proved the ability to activate GABA_A receptors synergistically. However, whether boropinol-B has neuroprotection in CI/RI remains unknown. Here we reported the neuroprotective effect of boropinol-B on CI/RI and its underlying mechanism, focusing on inhibiting inflammation and apoptosis. The oxygen and glucose deprivation and reperfusion (OGD/R) cell model showed that boropinol-B could improve cell viability, mitigate cell injury, and inhibit apoptosis. In rats, the transient ischemic model was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. Our results indicated that boropinol-B improved neurological scores, reduced cerebral infarction and neuronal necrosis of rats 24 h after ischemia, and prolonged median survival time after continuous administration for 14 days. Furthermore, we found that boropinol-B inhibited the over-activation of microglia and astrocytes, reduced the release of pro-inflammatory factors, and down-regulated the expression of matrix metalloproteinases-3/9, thus alleviating cerebral edema and blood-brain barrier dysfunction. Also, it suppressed apoptosis by increasing Bcl-2 expression and decreasing the expression of Bax, Active Caspase-3, and Cytochrome C. In conclusion, boropinol-B demonstrated anti-inflammatory and anti-apoptotic properties that contributed to the neuroprotective effect against CI/RI, suggesting that it may be an up-and-coming drug candidate to treat ischemic stroke.

Keywords: Apoptosis; Blood–brain barrier; Boropinol-B; Cerebral ischemia–reperfusion injury; Inflammation.