Artemisinin ameliorates experimental autoimmune prostatitis by suppressing NLRP3 inflammasome-induced pyroptosis via the Nrf2/HO-1 axis.

Abstract

Chronic prostatitis (CP) is common in young males. The etiology is unclear and treatment options are limited. Pyroptosis, a newly identified type of cell death, has been linked to CP pathogenesis, warranting further investigation. Here, the therapeutic effects of artemisinin (ART) on chronic non-specific inflammation were assessed. Comprehensive analyses, including evaluation of chronic pain progression, histopathology, and cytokine levels, revealed that ART significantly and dose-dependently suppressed NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and alleviated pathological damage in experimental autoimmune prostatitis. Mechanistic studies indicated that ART markedly reduced oxidative stress in autoimmune mouse models by stimulating the Nrf2/HO-1 axis. The effects of ART were blocked by a specific Nrf2/HO-1 inhibitor, preventing inflammasome-mediated induction of pyroptosis. Cellular experiments showed that ART elevated Nrf2 levels and suppressed NLRP3 inflammasome-mediated pyroptosis in RAW264.7 macrophages following lipopolysaccharide (LPS) stimulation. In summary, ART mitigates CP by modulating the Nrf2/HO-1 pathway, thereby reducing oxidative stress and suppressing NLRP3-inflammasome-induced pyroptosis.