title: Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.
abstract: BACKGROUND
  Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells.
  
  
  METHODS
  Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated.
  
  
  RESULTS
  RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-β, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1.
  
  
  CONCLUSIONS
  RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Kampeebhorn
authors.initials: K
authors.lastname: Boonloh
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Yonsei University Wonju College of Medicine, Wonju, 220-701, South Korea.
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Yonsei University Wonju College of Medicine, Wonju, 220-701, South Korea.
authors.forename: Hong Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Yonsei University Wonju College of Medicine, Wonju, 220-701, South Korea.
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Yonsei University Wonju College of Medicine, Wonju, 220-701, South Korea.
authors.forename: You Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Patchareewan
authors.initials: P
authors.lastname: Pannangpetch
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Bunkerd
authors.initials: B
authors.lastname: Kongyingyoes
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongviriyapan
authors.affiliation: Department of Food Technology, Faculty of Technology, Khon Kaen University, Khon Kaen, 40002, Thailand.
authors.forename: Supawan
authors.initials: S
authors.lastname: Thawornchinsombut
authors.affiliation: Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand. veerapol@kku.ac.th.
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Yonsei University Wonju College of Medicine, Wonju, 220-701, South Korea.
authors.forename: Choon Hee
authors.initials: CH
authors.lastname: Chung
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000276:immunology / Q000517:prevention & control*; D005525:Food-Processing Industry / Q000191:economics; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000191:economics / Q000378:metabolism / Q000627:therapeutic use*; D007220:Industrial Waste / Q000032:analysis / Q000191:economics; D007333:Insulin Resistance; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D050527:Mesangial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D012275:Oryza / Q000737:chemistry*; D019441:Plant Epidermis / Q000737:chemistry; D014674:Plant Proteins, Dietary / Q000191:economics / Q000378:metabolism / Q000627:therapeutic use*; D011492:Protein Hydrolysates / Q000191:economics / Q000378:metabolism / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000150:complications / Q000276:immunology / Q000517:prevention & control; D012639:Seeds / Q000737:chemistry; D013785:Thailand
chemical_list: D015415:Biomarkers; D007004:Hypoglycemic Agents; D007220:Industrial Waste; D014674:Plant Proteins, Dietary; D011492:Protein Hydrolysates
keywords: Angiogenesis; Diabetic nephropathy; Fibrosis; Inflammation; Insulin resistance; Rice bran