title: Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition.
abstract: OBJECTIVE
  Renal fibrosis is the common pathological foundation of many chronic kidney diseases (CKDs). The aim of this study was to investigate whether Hydroxysafflor yellow A (HSYA) can preserve renal function by inhibiting the progression of renal fibrosis and the potential mechanisms.
  
  
  METHODS
  Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on 7-week-old C57BL/6 mice. HSYA (10, 50 and 100 mg/kg) were intragastrically administered. Sham group and model group were administered with the same volume of vehicle. Serum and kidney samples were collected 14 days after the UUO surgery. Serum biochemical indicators were measured by automatic biochemical analyzer. Histological changes were evaluated by HE and Masson staining. In vitro, the anti-fibrotic effect of HSYA was tested on human recombinant transforming growth factor-β1 (TGF-β1) stimulated HK-2 cells. The protein levels of α-SMA, collagen-I and fibronectin in kidney tissue and HK-2 cells were measured by immunohistochemistry and immunofluorescence. The protein levels of apoptosis-relative and TGF-β1/Smad3 signaling were detected by western blot.
  
  
  RESULTS
  HSYA slowed the development of renal fibrosis both in vivo and in vitro. In UUO rats, renal function index suggested that HSYA treatment decreased the level of serum creatinine (Scr) and blood urea nitrogen (BUN) rose by UUO (P<0.05). HE staining and Masson staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration were notably attenuated in the high-dose HSYA group compared with the model group. The expressions of α-SMA, collagen-I and fibronectin were decreased in the UUO kidney and HK-2 cells of the HSYA-treatment group. Moreover, HSYA reduced the apoptotic rate of HK-2 cells stimulated by TGF-β1. Further study revealed that HSYA regulated the TGF-β1/Smads signaling pathway both in kidney tissue and HK-2 cells.
  
  
  CONCLUSIONS
  These results suggested that HSYA had a protective effect against fibrosis in renal cells, at least partly, through inhibiting TGF-β1/smad3-mediated Epithelial-mesenchymal transition signaling pathway.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Naping
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Meiyou
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.|College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis / Q000188:drug therapy / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy; D008297:Male; D008810:Mice, Inbred C57BL; D011809:Quinones / Q000494:pharmacology*; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*; D014517:Ureteral Obstruction / Q000473:pathology
chemical_list: D011809:Quinones; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D053773:Transforming Growth Factor beta1; C085278:hydroxysafflor yellow A; D002599:Chalcone; D003404:Creatinine