High levels of
reactive oxygen species (ROS), systemic T cell activation, and macrophage infiltration in the kidney are implicated in the acceleration and progression of
IgA nephropathy (IgAN), the most frequent type of primary
glomerulonephritis. However, the pathogenic mechanism of IgAN is still little understood, and it remains a challenge to establish a specific therapeutic strategy for this type of glomerular disorder. Recently, we showed that
antroquinonol (Antroq), a pure active compound from Antrodia camphorata mycelium, inhibits renal
inflammation and reduces oxidative stress in a mouse model of renal
fibrosis. But the anti-inflammatory and immune-regulatory effects of Antroq on the acceleration and progression of primary glomerular disorders have not been determined. In this study, we show that Antroq administration substantially impeded the development of severe renal lesions, such as intense glomerular proliferation, crescents,
sclerosis, and periglomerular interstitial
inflammation, in mice with induced accelerated and progressive IgAN (AcP-IgAN). Further mechanistic analysis in AcP-IgAN mice showed that, early in the developmental stage of the AcP-IgAN model, Antroq promoted the Nrf2
antioxidant pathway and inhibited the activation of T cells and NLRP3
inflammasome. Significantly improved
proteinuria/renal function and histopathology in AcP-IgAN mice of an established stage supported potential
therapeutic effects of Antroq on the disease. In addition, Antroq was shown to inhibit activation of NLRP3
inflammasome in vitro by an
IgA immune complex (IC) partly involving a reduced ROS production in
IgA-IC-primed macrophages, and this finding may be helpful in the understanding of the mode of action of Antroq in the treated AcP-IgAN mice.