PMID- 25880429 OWN - NLM STAT- MEDLINE DCOM- 20151029 LR - 20220410 IS - 1472-6882 (Electronic) IS - 1472-6882 (Linking) VI - 15 DP - 2015 Feb 22 TI - Oryeongsan suppressed high glucose-induced mesangial fibrosis. PG - 30 LID - 10.1186/s12906-015-0542-6 [doi] LID - 30 AB - 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 beta (TGF-beta)-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-kappaB translocation in HG-exposed mesangial cell. CONCLUSION: 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. FAU - Yoon, Jung Joo AU - Yoon JJ AD - 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. AD - Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. morality16@hanmail.net. FAU - Lee, Yun Jung AU - Lee YJ AD - 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. AD - Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. shrons@wku.ac.kr. FAU - Lee, So Min AU - Lee SM AD - 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. AD - Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. ashny86@hanmail.net. FAU - Kang, Dae Gill AU - Kang DG AD - 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. AD - Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. dgkang@wku.ac.kr. AD - 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. FAU - Lee, Ho Sub AU - Lee HS AD - 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. AD - Hanbang Body-fluid Research Center, Wonkwang University, Shinyong-dong, Iksan, Jeonbuk, 570-749, Republic of Korea. host@wku.ac.kr. AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150222 PL - England TA - BMC Complement Altern Med JT - BMC complementary and alternative medicine JID - 101088661 RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (Plant Extracts) RN - 0 (Smad Proteins) RN - 0 (TIMP2 protein, human) RN - 0 (Transforming Growth Factor beta) RN - 0 (wulingsan) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.80 (MMP14 protein, human) RN - EC 3.4.24.80 (Matrix Metalloproteinase 14) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Chemokine CCL2/metabolism MH - Diabetic Nephropathies/chemically induced/*drug therapy/metabolism MH - Fibrosis MH - Glomerular Mesangium/*drug effects/pathology MH - Glucose/administration & dosage/*adverse effects/metabolism MH - Inflammation/drug therapy/metabolism MH - Intercellular Adhesion Molecule-1/metabolism MH - *Magnoliopsida MH - Matrix Metalloproteinase 14/metabolism MH - Matrix Metalloproteinase 2/metabolism MH - Mesangial Cells/*drug effects/pathology MH - NF-kappa B/metabolism MH - Phytotherapy MH - Plant Extracts/pharmacology/*therapeutic use MH - *Polyporaceae MH - Rats MH - Signal Transduction/drug effects MH - Smad Proteins/metabolism MH - Tissue Inhibitor of Metalloproteinase-2/metabolism MH - Transforming Growth Factor beta/metabolism PMC - PMC4354744 EDAT- 2015/04/17 06:00 MHDA- 2015/10/30 06:00 PMCR- 2015/02/22 CRDT- 2015/04/17 06:00 PHST- 2014/07/03 00:00 [received] PHST- 2015/01/23 00:00 [accepted] PHST- 2015/04/17 06:00 [entrez] PHST- 2015/04/17 06:00 [pubmed] PHST- 2015/10/30 06:00 [medline] PHST- 2015/02/22 00:00 [pmc-release] AID - 10.1186/s12906-015-0542-6 [pii] AID - 542 [pii] AID - 10.1186/s12906-015-0542-6 [doi] PST - epublish SO - BMC Complement Altern Med. 2015 Feb 22;15:30. doi: 10.1186/s12906-015-0542-6.