title: Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy.
abstract: BACKGROUND
  Schisandra chinensis fruit is widely used in Chinese medicine for the treatment of hepatic, renal, heart, cerebrovascular and infectious diseases.
  
  
  OBJECTIVE
  To investigate the effects of Schisandra chinensis fruit extract (SE) on albuminuria and podocyte injury as well as the underlying mechanism in the mouse model of streptozotocin (STZ)-induced diabetic nephropathy and in cultured mouse podocyte cells.
  
  
  METHODS
  SE was orally administrated in STZ-induced diabetic nephropathy mice for 7 weeks, at a daily dose of 5g/kg body weight. The urinary albumin/creatinine ratio and urine albumin excretion rate were measured at the 6th and 9th week of the experiment. The extent of glomerulosclerosis and extracellular matrix deposition were determined by periodic acid-silver methenamine and Masson's trichrome staining. The amount of podocytes and the integrity of the slit diaphragm were detected by immunohistological staining of podocyte markers, Wilms' tumor 1 and nephrin. Alpha-smooth muscle actin, E-cadherin and plasminogen activator inhibitor-1 were measured by western blot and immunohistological staining to evaluate the level of epithelial-to-mesenchymal transition (EMT). Real-time reverse transcription PCR was used to detect the mRNA level of E-cadherin, alpha-SMA and snail in cultured podocyte cells.
  
  
  RESULTS
  Treatment with SE significantly decreased the urine albumin excretion rate and urinary albumin/creatinine ratio. In addition, SE attenuated glomerulosclerosis and protected against podocyte loss and integrity of the slit diaphragm. Furthermore, SE effectively prevented the EMT of podocytes caused by diabetic nephropathy.
  
  
  CONCLUSIONS
  Our studies suggest that SE might be beneficial for diabetic nephropathy. The effects of SE on attenuating albuminuria and glomerulosclerosis are possibly mediated by preserving podocyte integrity through suppressing EMT.
authors.affiliation: Nephrology Division, Gongan Hospital, 78 Nanjin Road, Tianjin 300040, China.
authors.forename: Mianzhi
authors.initials: M
authors.lastname: Zhang
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Xiong
authors.forename: Junbo
authors.initials: J
authors.lastname: Gong
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Tan
mesh_terms: D000284:Administration, Oral; D000419:Albuminuria / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005638:Fruit; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032141:Schisandra / Q000737:chemistry; D013997:Time Factors
chemical_list: D015415:Biomarkers; D010936:Plant Extracts; D020011:Protective Agents; D012333:RNA, Messenger