Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome

Shun Min Yang, Shuk Man Ka, Kuo Feng Hua, Tzu Hua Wu, Yi Ping Chuang, Ya Wen Lin, Feng Ling Yang, Shih Hsiung Wu, Sung Sen Yang, Shih Hua Lin, Jia Ming Chang, Ann Chen

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)285-297
Number of pages13
JournalFree Radical Biology and Medicine
Volume61
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Inflammasomes
T-cells
Immunoglobulin A
T-Lymphocytes
Kidney
Macrophages
Chemical activation
Antigen-Antibody Complex
Reactive Oxygen Species
Antrodia
Inflammation
Oxidative stress
Macrophage Activation
Mycelium
Sclerosis
Therapeutic Uses
Glomerulonephritis
antroquinonol
Proteinuria
Infiltration

Keywords

  • Accelerated and progressive IgA
  • Antroquinonol
  • Free radicals
  • Macrophage
  • nephropathy
  • NLRP3 inflammasome
  • Nrf2
  • ROS
  • T cell

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome. / Yang, Shun Min; Ka, Shuk Man; Hua, Kuo Feng; Wu, Tzu Hua; Chuang, Yi Ping; Lin, Ya Wen; Yang, Feng Ling; Wu, Shih Hsiung; Yang, Sung Sen; Lin, Shih Hua; Chang, Jia Ming; Chen, Ann.

In: Free Radical Biology and Medicine, Vol. 61, 2013, p. 285-297.

Research output: Contribution to journalArticle

Yang, Shun Min ; Ka, Shuk Man ; Hua, Kuo Feng ; Wu, Tzu Hua ; Chuang, Yi Ping ; Lin, Ya Wen ; Yang, Feng Ling ; Wu, Shih Hsiung ; Yang, Sung Sen ; Lin, Shih Hua ; Chang, Jia Ming ; Chen, Ann. / Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome. In: Free Radical Biology and Medicine. 2013 ; Vol. 61. pp. 285-297.
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T1 - Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome

AU - Yang, Shun Min

AU - Ka, Shuk Man

AU - Hua, Kuo Feng

AU - Wu, Tzu Hua

AU - Chuang, Yi Ping

AU - Lin, Ya Wen

AU - Yang, Feng Ling

AU - Wu, Shih Hsiung

AU - Yang, Sung Sen

AU - Lin, Shih Hua

AU - Chang, Jia Ming

AU - Chen, Ann

PY - 2013

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N2 - 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.

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KW - T cell

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