Antimalarial Drug Artemisinin Extenuates Amyloidogenesis and Neuroinflammation in APPswe/ PS1dE9 Transgenic Mice via Inhibition of Nuclear Factor-κ B and NLRP3 Inflammasome Activation.

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. [ABSTRACT FROM AUTHOR]