title: Ruscogenin ameliorates diabetic nephropathy by its anti-inflammatory and anti-fibrotic effects in streptozotocin-induced diabetic rat.
abstract: BACKGROUND
  Ruscogenin is a major steroid sapogenin in the traditional Chinese herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have demonstrated that ruscogenin is involved in down-regulation of intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) activation in anti-inflammatory pathways. We hypothesized that ruscogenin protects against diabetic nephropathy (DN) by inhibiting NF-κB-mediated inflammatory pathway. To test this hypothesis, the present study was to examine the effects of ruscogenin in rats with streptozotocin (STZ)-induced DN.
  
  
  METHODS
  Diabetes was induced with STZ (60 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats in the treatment group were orally dosed with 0.3, 1.0 or 3.0 mg/kg ruscogenin for 8 weeks. The normal rats were chosen as nondiabetic control group. The rats were sacrificed 10 weeks after induction of diabetes. Changes in renal function-related parameters in plasma and urine were analyzed at the end of the study. Kidneys were isolated for pathology histology, immunohistochemistry, and Western blot analyses.
  
  
  RESULTS
  Ruscogenin administration did not lower the levels of plasma glucose and glycosylated hemoglobin in STZ-diabetic rats. Diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine clearance, blood urea nitrogen and proteinuria, along with marked elevation in the ratio of kidney weight to body weight, that were reversed by ruscogenin. Ruscogenin treatment was found to markedly improve histological architecture in the diabetic kidney. Renal NF-κB activity, as wells as protein expression and infiltration of macrophages were increased in diabetic kidneys, accompanied by an increase in protein content of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 in kidney tissues. All of the above abnormalities were reversed by ruscogenin treatment, which also decreased the expression of transforming growth factor-β1 and fibronectin in the diabetic kidneys.
  
  
  CONCLUSIONS
  Our data demonstrated that ruscogenin suppressed the inflammation and ameliorated the structural and functional abnormalities of the diabetic kidney in rats might be associated with inhibition of NF-κB mediated inflammatory genes expression.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Lu
authors.forename: Thing-Fong
authors.initials: TF
authors.lastname: Tzeng
authors.forename: Shorong-Shii
authors.initials: SS
authors.lastname: Liou
authors.forename: Sheng
authors.initials: S
authors.lastname: Da Lin
authors.affiliation: Department of Food Science, College of Agriculture, National Pingtung University of Science and Technology, Pingtung County, Taiwan. mcwu@mail.npust.edu.tw.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Wu
authors.forename: I-Min
authors.initials: IM
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D031441:Ophiopogon / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D015398:Signal Transduction; D013150:Spirostans / Q000494:pharmacology* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D005353:Fibronectins; D016328:NF-kappa B; D010936:Plant Extracts; D013150:Spirostans; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; C012541:ruscogenin