The combination of astragaloside IV and Panax notoginseng saponins attenuates cerebral ischaemia-reperfusion injury in rats through ferroptosis and inflammation inhibition via activating Nrf2

Objectives: This study aimed to observe the effect of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on cerebral ischaemia-reperfusion injury (CIRI) and explore the specific mechanism of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated combination of AST IV and PNS against CIRI based on Ferroptosis and inflammatory response.

Methods: The therapeutic effect and mechanism of AST IV and PNS were evaluated by constructing a Sprague-Dawley rat middle cerebral artery ischaemia-occlusion-reperfusion model. The specific mechanism of the combination of AST IV and PNS against CIRI was revealed through the combined intervention of the Nrf2-specific inhibitor brusatol.

Key findings: After AST IV and PNS treatment, the cerebral infarction area of the rats was reduced; behavioural performance was improved; Fe2+, malondialdehyde, lipid peroxidation, interleukin-6, interleukin-1β, tumour necrosis factor-α and myeloperoxidase levels were reduced; and glutathione and Glutathione Peroxidase 4 levels were increased. In addition, the expression of Nrf2 was significantly increased, the combined treatment was more effective than the single treatment, and the Nrf2 inhibitor brusatol could reverse the effects of the combined intervention of AST IV and PNS.

Conclusions: The findings of this study suggest that combining AST IV and PNS attenuates CIRI by activating Nrf2 to inhibit Ferroptosis and inflammatory responses.

Panax notoginseng saponins; astragaloside IV; cerebral ischaemia–reperfusion injury; ferroptosis; inflammatory; nuclear factor erythroid 2-related factor 2.