Astragalus Polysaccharide Alleviates Oxidative Stress Injury through Modulation of the Nrf2/HO-1 Axis in the Striatum of Cerebral Ischemic Rats
TL;DR
APS effectively mitigated neuronal damage and motor dysfunction after cerebral ischemia and improved neurological function and ameliorated neuronal damage in rats subjected to middle cerebral artery occlusion.
Abstract
Abstract Objective Astragalus polysaccharide (APS) has therapeutic potential for neurodegenerative diseases; however, its specific mechanism of action against ischemic stroke (IS) requires further elucidation. This study aimed to elucidate the protective effects of APS on neural tissue and to explore the underlying molecular pathways in a rat population subjected to middle cerebral artery occlusion (MCAO) Methods The animals received intraperitoneal (IP) injections of APS. Neurological recovery was assessed using neurobehavioral tests, and neuronal morphology was examined using Nissl staining. Then, we assessed the mRNA levels of IL-1β, IL-6, and TNF-α as well as the concentrations of oxidative stress-related substances. Finally, we evaluated the expression levels of Nrf2, Keap1, HO-1, and GPX4 through Western blotting and immunofluorescence. Results APS improved neurological function and ameliorated neuronal damage. It concurrently inhibited IL-1β, IL-6, and TNF-α expression while enhancing antioxidative potential. Mechanistically, APS induced an elevation in the levels of Nrf2, HO-1, and GPX4 proteins while concurrently causing a reduction in the protein levels of Keap1 in the striatum. Conclusions APS effectively mitigated neuronal damage and motor dysfunction after cerebral ischemia. The protective mechanism involves the activation of the Nrf2/HO-1 axis and subsequent suppression of oxidative stress and neuroinflammation.