Alpha-mangostin alleviate renal interstitial fibrosis via suppression of TGF-β1/Smad/ERK signaling axis in vitro and in vivo

α-mangostin (α-MG), a natural derivative of coumarin, exhibits anti-inflammatory, antioxidant and anti-fibrotic effects. This study aimed to determine the effect of α-MG treatment in mediating the process of renal interstitial fibrosis. We found that α-MG could alleviate tubule-interstitial damage a...

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Bibliographic Details
Published in:Biochemical pharmacology 2023-12, Vol.218, p.115935-115935, Article 115935
Main Authors: Juan, Ying-Hsu, Yu, Yung-Luen, Tsai, Yuan-Pei, Lee, Chu-Che, Chen, Yong-Syuan, Ting, Yi-Hsuan, Tsai, Jen-Pi, Hsieh, Yi-Hsien
Format: Article
Language:English
Subjects:
Animals
Epithelial-Mesenchymal Transition
Fibrosis
Kidney - metabolism
Mice
Renal Insufficiency, Chronic - metabolism
Signal Transduction
Smad Proteins - metabolism
Transforming Growth Factor beta1 - metabolism
Ureteral Obstruction - metabolism
Ureteral Obstruction - pathology
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Summary:α-mangostin (α-MG), a natural derivative of coumarin, exhibits anti-inflammatory, antioxidant and anti-fibrotic effects. This study aimed to determine the effect of α-MG treatment in mediating the process of renal interstitial fibrosis. We found that α-MG could alleviate tubule-interstitial damage and decrease fibrotic (α-smooth muscle actin [α-SMA], fibronectin, and collagen I), and epithelial-mesenchymal transition (EMT) protein (N-cadherin, Snail, Slug, TGF-β1 and vimentin) expression in unilateral ureteral obstruction (UUO) mice with chronic kidney disease. α-MG significantly decreased motility as well as inhibited expression of fibrotic- and EMT-related proteins in TGF-β1-induced HK2 cells. To clarify the molecular mechanisms of α-MG in reducing renal interstitial fibrosis, we used a MEK inhibitor (U0126) or Smad inhibitor (SB431542) cotreatment with α-MG. This is the first study is to demonstrate the antifibrotic effects of α-MG by targeting the TGF-β1/ERK/Smad-mediated EMT signaling pathway, is even more effective against renal interstitial fibrosis.
ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2023.115935