Antimalarial Drug Artemisinin Extenuates Amyloidogenesis and Neuroinflammation in APPswe/PS1dE9 Transgenic Mice via Inhibition of Nuclear Factor‐κB and NLRP3 Inflammasome Activation

Summary Background The activation of nuclear factor‐kappa B (NF‐κB) and NLRP3 inflammasome is involved in neuroinflammation, which is closely linked to Alzheimer's disease (AD). In vivo and in vitro studies have suggested that artemisinin shows antiinflammatory effects in inflammation‐related diseases. However, the impacts of artemisinin on AD have not been investigated. Aims In this study, 5‐month‐old APPswe/PS1dE9 transgenic mice were treated daily with 40 mg/kg artemisinin for 30 days by intraperitoneal injection to evaluate the effects of artemisinin on AD. Results We found that artemisinin treatment (1) decreased neuritic plaque burden; (2) did not alter Aβ transport across the blood–brain barrier; (3) regulated APP processing via inhibiting β‐secretase activity; (4) inhibited NF‐κB activity and NALP3 inflammasome activation in APPswe/PS1dE9 double transgenic mice. Conclusions The in vivo study clearly demonstrates that artemisinin has protective effects on AD pathology due to its effects on suppressing NF‐κB activity and NALP3 inflammasome activation. Our study suggests that targeting NF‐κB activity and NALP3 inflammasome activation offers a valuable intervention for AD.