Rui Feng, Andong Zhang, Yiming Li, Peng Wang, Hui Guo, Yonghong Hu, Mingyue Tan, Dongliang Xu
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.