Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 50, Issue 11, Pages 1503-1516Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2011.02.029
Keywords
Antroquinonol; Antrodia camphorata; Glomerular sclerosis; Epithelial hyperplasia lesion; Podocyte injury; Oxidative stress; Nuclear factor E2-related factor 2; Nuclear factor-kappa B; Transforming growth factor-beta 1; Free radicals
Funding
- National Science Council, Executive Yuan [NSC-099-2811-B016]
- Tri-Service General Hospital, Taiwan, ROC [TSGH-C99-011-015-S01]
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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-kappa B (NF-kappa B) activation and decreases levels of transforming growth factor (TGF)-beta 1 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-kappa B-dependent inflammatory and TGF-beta 1-mediated fibrosis pathways in the kidney. (C) 2011 Elsevier Inc. All rights reserved.
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