Alpha-mangostin alleviate renal interstitial fibrosis via suppression of TGF-1/Smad/ERK signaling axis in vitro and in vivo

alpha-mangostin (alpha-MG), a natural derivative of coumarin, exhibits anti-inflammatory, antioxidant and anti-fibrotic effects. This study aimed to determine the effect of alpha-MG treatment in mediating the process of renal interstitial fibrosis. We found that alpha-MG could alleviate tubule-interstitial damage and decrease fibrotic (alpha-smooth muscle actin [alpha-SMA], fibronectin, and collagen I), and epithelial-mesenchymal transition (EMT) protein (N-cadherin, Snail, Slug, TGF-beta 1 and vimentin) expression in unilateral ureteral obstruction (UUO) mice with chronic kidney disease. alpha-MG significantly decreased motility as well as inhibited expression of fibrotic-and EMT-related pro -teins in TGF-beta 1-induced HK2 cells. To clarify the molecular mechanisms of alpha-MG in reducing renal interstitial fibrosis, we used a MEK inhibitor (U0126) or Smad inhibitor (SB431542) cotreatment with alpha-MG. This is the first study is to demonstrate the antifibrotic effects of alpha-MG by targeting the TGF-beta 1/ERK/Smad-mediated EMT signaling pathway, is even more effective against renal interstitial fibrosis.