Neuroprotective Effect of Andrographolide against Ischemic Stroke in Rats Through Reducing Inos and gp91(superscript phox)/NOX2 Expression

Abstract

Andrographolide, an active component isolated from Andrographis paniculata, has been reported to exhibit anti-inflammatory effects in neutrophils and microglial cells, but its effects on central nervous system (CNS) are unclear. In this study, we explored the CNS protective effect of andrographolide in an ischemic stroke animal model. We performed a cerebral ischemic/reperfusion (CI/R) injury in rats to study whether treatment of andrographolide (5-10 μg/kg, i.v.) 1 h after ischemia could protect rats against stroke. Treatment with andrographolide dose-dependently ameliorated CI/R-induced brain infarction (reduced by 32%~51%) and improved neurological deficits in rats at day 1 after stroke. Elevated pathophysiological markers including reactive oxygen species (ROS) production and protein nitrosylation were significantly reduced by andrographolide. CI/R dramatically enhanced expression of inducible nitric oxide synthase (iNOS), gp91(superscript phox)/NADPH oxidase 2 (NOX2) and interleukin-1β (IL-1β) that paralleled to the activation of nuclear factor-kappa B (NF-κB) and hypoxia-inducing factor 1-alpha (HIF-1α), and all were significantly diminished by andrographolide. Andrographolide compromises CI/R induced expression of iNOS and gp91(superscript phox)/NOX2 through impairing NF-κB and HIF-1α activation that confers it as a potential ischemic stroke therapeutic agent.