Paeoniflorin of Paeonia lactiflora prevents renal interstitial fibrosis induced by unilateral ureteral obstruction in mice

摘要

Paeoniflorin (PF), the major active constituent of Paeonia lactiflora Pallas, has previously been reported to alleviate hepatic fibrosis. Whether and how it affects renal fibrosis was evaluated in the present study. The experimental renal fibrosis was induced by unilateral ureteral obstruction (UUO) operation in mice, and PF was orally administered for consecutive 7 days. Renal interstitial destruction and fibrosis degree were evaluated by histopathological examination and hydroxyproline assay. It was shown that PF treatment markedly ameliorated renal interstitial fibrotic lesions, attenuated synthesis of collagen and plasminogen activator inhibitor-1 (PAI-1), an important inhibitor of extracellular matrix degrading enzymes, in UUO mice. PF also suppressed epithelial-mesenchymal transition (EMT) by down-regulating TGF-β1 expression and maintaining BMP-7 mRNA expression, and inhibited Smad2/3 activation in fibrotic kidneys induced by UUO. These observations suggest that PF can effectively prevent renal interstitial fibrosis, and the underlying mechanisms are, at least in part, through blocking EMT via BMP-7 recovery and TGF-β/Smad signaling inhibition.