Antroquinonol reduces oxidative stress by enhancing the Nrf2 signaling pathway and inhibits inflammation and sclerosis in focal segmental glomerulosclerosis mice.

Abstract

Oxidative stress, inflammation, and fibrosis are involved in the development and progression of focal segmental glomerulosclerosis (FSGS), a common form of idiopathic nephrotic syndrome that represents a therapeutic challenge because it has a poor response to steroids. Antroquinonol (Antroq), a purified compound, is a major active component of a mushroom, namely Antrodia camphorata, that grows in the camphor tree in Taiwan, and it has inhibitory effects on nitric oxide production and inflammatory reactions. We hypothesized that Antroq might ameliorate FSGS renal lesions by modulating the pathogenic pathways of oxidative stress, inflammation, and glomerular sclerosis in the kidney. We demonstrate that Antroq significantly (1) attenuates proteinuria, renal dysfunction, and glomerulopathy, including epithelial hyperplasia lesions and podocyte injury; (2) reduces oxidative stress, leukocyte infiltration, and expression of fibrosis-related proteins in the kidney; (3) increases renal nuclear factor E2-related factor 2 (Nrf2) and glutathione peroxidase activity; and (4) inhibits renal nuclear factor-κB (NF-κB) activation and decreases levels of transforming growth factor (TGF)-β1 in serum and kidney tissue in a mouse FSGS model. Our data suggest that Antroq might be a potential therapeutic agent for FSGS, acting by boosting Nrf2 activation and suppressing NF-κB-dependent inflammatory and TGF-β1-mediated fibrosis pathways in the kidney.

• Authors: Pei-Yi Tsai, Shuk-Man Ka, Tai-Kuang Chao, Jia-Ming Chang, Shih-Hua Lin, Chen-Yun Li, Mao-Tien Kuo, Peini Chen, Ann Chen
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 50 Issue 11 Pg. 1503-16 (Jun 01 2011) ISSN: 1873-4596 [Electronic] United States
• PMID: 21376112 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• NF-E2-Related Factor 2
• NF-kappa B
• Transforming Growth Factor beta1
• Ubiquinone
• antroquinonol

Topics

• Animals
• Antrodia
• Disease Models, Animal
• Female
• Focal Epithelial Hyperplasia (prevention & control)
• Glomerulosclerosis, Focal Segmental (drug therapy, pathology, physiopathology)
• Humans
• Inflammation (prevention & control)
• Kidney (drug effects, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• NF-E2-Related Factor 2 (genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Oxidative Stress (drug effects)
• Sclerosis (prevention & control)
• Signal Transduction (drug effects)
• Transforming Growth Factor beta1 (metabolism)
• Ubiquinone (administration & dosage, analogs & derivatives)