Astragaloside IV improves cognitive impairment caused by CCH via improve ROS and NLRP3 pathway by up-regulating the PGC1α/Nrf2 pathway

Abstract

Abstract This study was conducted to elucidate the possible molecular mechanisms of neuroprotective effect of Astragaloside IV (As-IV) on animal models of Vascular Dementia . Oxidative damage and neuroinflammation play a key role in chronic cerebral hypoperfusion (CCH) and lead to a decline in cognitive function in animals. In the present study, Sprague Dawley (SD) rats were randomly divided into sham group, model group, As-IV20 group, and As-IV50 group, with 10 rats in each group. The Morris water maze (MWM) was used to evaluate the cognitive function of rats. The nitrogen-blue tetrazolium photoreduction method was employed to detect the levels of superoxide dismutase (SOD) in the hippocampal tissue homogenate. The bituric acid method was utilised to detect the malondialdehyde (MDA) levels. Western blotting was performed to evaluate the levels of stimulator of interferon genes (Sting), NOD-like receptor protein 3 (NLRP3)，Caspase-1 and Peroxisome proliferator-activated receptor gamma co-activator-1α (PGC-1α)，and transcription factors such as nuclear factor erythroid-derived factor-2 (Nrf2) in hippocampus tissues. The results indicate that As-IV supplementation significantly regulates the above changes. In addition, As-IV treatment effectively up-regulates the PGC-1α and Nrf2. Overall, our findings suggest that As-IV can effectively improve the cognitive impairment caused by CCH and oxidative damage. Furthermore, mitochondrial damage and inflammation against CCH may be attributed to the activation of the PGC-1α/Nrf2 signalling pathway to reduce ROS. This activation can reduce neuroinflammation caused by Sting/NLRP3/caspase1 pathway.