IgA Nephropathy Benefits from Compound K Treatment by Inhibiting NF-κB/NLRP3 Inflammasome and Enhancing Autophagy and SIRT1
Chung-Yao Wu, Kuo‐Feng Hua, Wan-Han Hsu, Yusuke Suzuki, Lichieh Julie Chu, Yu-Chieh Lee, Akiko Takahata, Sheau-Long Lee, Chia‐Chao Wu, David J. Nikolic‐Paterson, Shuk‐Man Ka, Ann Chen
Abstract
IgA nephropathy (IgAN), the most common primary glomerular disorder, has a relatively poor prognosis yet lacks a pathogenesis-based treatment. Compound K (CK) is a major absorbable intestinal bacterial metabolite of ginsenosides, which are bioactive components of ginseng. The present study revealed promising therapeutic effects of CK in two complementary IgAN models: a passively induced one developed by repeated injections of IgA immune complexes and a spontaneously occurring model of spontaneous grouped ddY mice. The potential mechanism for CK includes 1) inhibiting the activation of NLRP3 inflammasome in renal tissues, macrophages and bone marrow-derived dendritic cells, 2) enhancing the induction of autophagy through increased SIRT1 expression, and 3) eliciting autophagy-mediated NLRP3 inflammasome inhibition. The results support CK as a drug candidate for IgAN.