Astragaloside IV (AS-IV) is the main active component isolated from the traditional Chinese medicinal herb Astragalus membranaceus. Studies have demonstrated that AS-IV has
neuroprotective effects in cerebral ischemic models. In this study, we aimed to investigate the effects of AS-IV on memory impairment induced by
transient cerebral ischemia and reperfusion in mice, as well as the associated signaling mechanisms. Severe
memory deficits were induced by bilateral common carotid artery occlusion (BCCAO) in mice as indicated in the Morris water maze test in this study.
Oral administration of AS-IV (10 and 20mg/kg, once per day, started 7days before surgery and continued for 7days after surgery) significantly attenuated memory impairment and
neuroinflammation. Moreover, AS-IV treatment significantly reduced the expression of toll-like receptor-4 (TLR4) and its downstream adaptor
proteins, including myeloid differentiation primary response gene 88 (MyD88), toll/
interleukin-1 receptor-domain containing adaptor-inducing
interferon-β (TRIF) and tumour
necrosis factor receptor associated factor-6 (
TRAF6), and subsequently inhibited NF-κB phosphorylation. It is well-known that
cerebral ischemia and
reperfusion injury enhances the formation of
reactive oxygen species (ROS) and further
neuroinflammation. Importantly, we found that AS-IV suppressed NLRP3
inflammasome activation by controlling ROS production. In addition, AS-IV markedly reduced overactivation of microglia and the overexpression of inflammatory
cytokines in the hippocampus compared with the
transient cerebral ischemia and reperfusion group. These results suggest that AS-IV might possess
neuroprotective effects against
transient cerebral ischemia and reperfusion partly through its anti-inflammatory effects by inhibiting TLR4 signaling pathway and NLRP3
inflammasome overactivation.