Mar 24, 2020

Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia

Acta Pharmacologica Sinica
Man LiZhi-Fei Wang

Abstract

Cycloastragenol (CAG) is the active form of astragaloside IV isolated from Astragalus Radix, which displays multiple pharmacological effects. Silent information regulator 1 (SIRT1), a class III histone deacetylase, has been shown to play an important role in neuroprotection against cerebral ischemia. In this study, we investigated whether CAG protected against ischemic brain injury and, if so, whether the beneficial effects were associated with the regulation of SIRT1 in the ischemic brain. Mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. CAG (5, 10, 20 mg/kg) was injected intraperitoneally at the onset of reperfusion, 12 h later and then twice daily for up to three days. CAG dose-dependently reduced brain infarct volume, significantly ameliorated functional deficits, and prevented neuronal cell loss in MCAO mice. Meanwhile, CAG significantly reduced matrix metalloproteinase-9 activity, prevented tight junction degradation and subsequently ameliorated blood-brain barrier disruption. Moreover, CAG significantly upregulated SIRT1 expression in the ischemic brain but did not directly activate its enzymatic activity. Concomitant with SIRT1 upregulation, CAG reduced p53 acetylation an...Continue Reading

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Mentioned in this Paper

Inflammation
Blood - Brain Barrier Anatomy
Plant Roots
Finding
Neurons
Histone Deacetylase
SIR1 protein, S cerevisiae
Matrix Metalloproteinase 9
SIRT1
HDAC1

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