title: An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats.
abstract: BACKGROUND
  Currently, no drug is available to directly target the signaling molecules involved in the pathogenesis of diabetic nephropathy (DN); only antihypertensive and antidiabetic drugs are in clinical use. In the present study, the therapeutic effects of a active fraction of tubers from Pueraria tuberosa (hereafter referred to as PTY-2) were investigated in streptozotocin (STZ)-diabetic rats with DN, with particular emphasis on its effects on extracellular matrix (ECM) accumulation and matrix metalloproteinase (Mmp)-9 expression in kidney tissue.
  
  
  METHODS
  Rats were injected with 55 mg/kg, i.p., STZ. After 40 days, rats were divided into groups as follows (n = 6 per group): Group 1, age-matched rats not injected with STZ (non-diabetic control); Group 2, STZ-diabetic DN rats; and Group 3, PTY-2 (30 mg/100 g, p.o.)-treated DN rats. After 20 days treatment, the effects of PTY-2 on serum urea and creatinine concentrations, urinary levels of glucose, creatinine, protein, and ketone bodies, and urine pH were determined. Kidney tissue was evaluated for Mmp-9 expression and histological changes.
  
  
  RESULTS
  Blood glucose, serum urea, creatinine, and urine protein levels were significantly higher, and creatinine clearance was significantly lower, in Group 2 versus Group 1 rats. There was a higher degree of glomerulosclerosis, expansion of the mesangial matrix, and excess ECM deposition and eosinophilic casts in kidneys from Group 2 versus Group 1 rats. Furthermore, Mmp-9 activity and expression were significantly reduced in kidney homogenate of Group 2 versus Group 1 rats. Interestingly, PTY-2 treatment significantly reversed all these changes in DN rats.
  
  
  CONCLUSIONS
  Treatment of DN rats with PTY-2 significantly attenuated the severity of DN by increasing the expression and activity of Mmp-9, consequently degrading the ECM accumulated in kidney tissue.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Varanasi, 221005, India.
authors.forename: Yamini B
authors.initials: YB
authors.lastname: Tripathi
authors.affiliation: Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Varanasi, 221005, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Shukla
authors.affiliation: Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Varanasi, 221005, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Pandey
authors.affiliation: Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Sciences, Varanasi, 221005, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Pandey
authors.affiliation: Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Mohan
authors.initials: M
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D007657:Ketone Bodies / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology*; D035281:Plant Tubers / Q000737:chemistry*; D029908:Pueraria / Q000737:chemistry*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015854:Up-Regulation / Q000187:drug effects; D014508:Urea / Q000097:blood; D014556:Urine / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D007657:Ketone Bodies; D010936:Plant Extracts; D014508:Urea; D003404:Creatinine; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D005947:Glucose
keywords: Ayurveda; Pueraria tuberosa; diabetic nephropathy; functional food; proteinuria