Open AccessIcariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway
Author(s) -
Zhang Lei,
Wang XingZhi,
Li YuShu,
Zhang Lei,
Hao LiRong
Publication year - 2017
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12161
Subject(s) - icariin , epimedium , proinflammatory cytokine , chemistry , medicine , inflammasome , nephropathy , endocrinology , blood urea nitrogen , proteinuria , pharmacology , creatinine , kidney , inflammation , traditional medicine , pathology , alternative medicine , herb , diabetes mellitus , medicinal herbs
Immunoglobulin A nephropathy (Ig AN ) is the most frequent form of glomerulonephritis, which is characterized by glomerular proliferation and renal inflammation. Icariin is a flavonoid from the Chinese herb Epimedium, and its anti‐inflammatory effect has been reported. This study aimed to investigate the effects of icariin on the renal damage in Ig AN rats and the mechanisms behind these effects. Ig AN model was established in Sprague–Dawley rats by oral and intravenous immunization with bovine gamma‐globulin for 12 weeks, and rats were treated with icariin from 12 to 18 weeks. At the end of experimental period, kidneys, urine, and blood samples were collected for further analysis. Our results showed that icariin ameliorated the increase in the levels of proteinuria, serum creatinine, and urea nitrogen without severe side effects. Ig AN rats exhibited significantly increased IgA deposition, mesangial matrix expansion, and glomerular fibrosis, while icariin treatment markedly attenuated these alterations. Moreover, treatment with icariin also dramatically blocked nuclear factor kappa b ( NF ‐κB) nuclear translocation and Nlrp3 inflammasome activation in Ig AN rats, leading to reduced downstream proinflammatory cytokines production. Mechanistically, we found that icariin treatment inhibited IKK β and IκBα phosphorylation and IκBα degradation in Ig AN rats. Our data demonstrate that icariin ameliorates renal damage in Ig AN rats via inhibition of NF ‐κB‐mediated Nlrp3 inflammasome activation. These findings provide insight into an application of icariin for the treatment of Ig AN disease, and represent a novel mechanism behind these effects.