title: Oryeongsan suppressed high glucose-induced mesangial fibrosis.
abstract: BACKGROUND
  The pathological change of kidney in diabetic nephropathy is represented hypertrophy, inflammation, and renal fibrosis. Oryeongsan, traditional oriental herbal formula, is widely used for the treatment of nephrosis, dropsy, and uremia. This study was examined whether Oryeongsan attenuate high-glucose (HG)-promoted rat mesangial cell fibrosis and matrix accumulation, major features of diabetic glomerulosclerosis.
  
  
  METHODS
  Oryeongsan was mixed traditional herbal medicine, Alisma orientale Juz, Polyporus umbellatus Fries, Atractylodes macrocephala Koidez, Poria cocos Wolf and Cinnamomum Cassia Presl (5:3:3:1). Renoprotective role in diabetic nephropathy of Oryeongsan was evaluated by [(3)H]-thymidine incorporation, Western blot, RT-qPCR and immunofluorescence microscopy assay.
  
  
  RESULTS
  Rat mesangial cell proliferation induced by HG was significantly accelerated, which was inhibited by Oryeongsan in a dose dependent manner. HG enhanced expression of fibrosis biomarkers such as collagen IV and connective tissue growth factor (CTGF), which was markedly attenuated by Oryeongsan. Oryeongsan increased HG-inhibited membrane type-1 matrix metalloproteinase expression (MT1-MMP) and MMP-2 promotor activity, whereas suppressed HG-induced tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) expression. Moreover, Oryeongsan promoted extracellular matrix degradation through disturbing transforming growth factor β (TGF-β)-Smad signaling. This study further revealed that Oryeongsan ameliorated HG-induced mesangial inflammation accompanying induction of intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Moreover, pretreatment of Oryeongsan inhibited NF-κB translocation in HG-exposed mesangial cell.
  
  
  CONCLUSIONS
  These results demonstrate that Oryeongsan has protective effect against renal proliferation, fibrosis, and inflammation. Therefore Oryeongsan may be specific therapies targeting renal dysfunction leading to diabetic nephropathy.
authors.affiliation: Professional Graduate School of Oriental Medicine and College of Oriental Medicine, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. morality16@hanmail.net.|Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. morality16@hanmail.net.
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Yoon
authors.affiliation: Professional Graduate School of Oriental Medicine and College of Oriental Medicine, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. shrons@wku.ac.kr.|Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. shrons@wku.ac.kr.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Professional Graduate School of Oriental Medicine and College of Oriental Medicine, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. ashny86@hanmail.net.|Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. ashny86@hanmail.net.
authors.forename: So Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Professional Graduate School of Oriental Medicine and College of Oriental Medicine, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. dgkang@wku.ac.kr.|Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. dgkang@wku.ac.kr.|Brain Korea (BK) 21 plus team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, 540-749, Republic of Korea. dgkang@wku.ac.kr.
authors.forename: Dae Gill
authors.initials: DG
authors.lastname: Kang
authors.affiliation: Professional Graduate School of Oriental Medicine and College of Oriental Medicine, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. host@wku.ac.kr.|Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. host@wku.ac.kr.|Brain Korea (BK) 21 plus team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk, 540-749, Republic of Korea. host@wku.ac.kr.
authors.forename: Ho Sub
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005355:Fibrosis; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000473:pathology; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019684:Magnoliopsida; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011124:Polyporaceae; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016328:NF-kappa B; D010936:Plant Extracts; D051785:Smad Proteins; C560823:TIMP2 protein, human; D016212:Transforming Growth Factor beta; C443861:wulingsan; D018799:Intercellular Adhesion Molecule-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D005947:Glucose