title: Renoprotective effect of Hypericum perforatum against diabetic nephropathy in rats: Insights in the underlying mechanisms.
abstract: Oxidative stress and inflammation play a key role in the initiation and progression of diabetic nephropathy (DN). The present study aimed to investigate the possible protective effect of hypericum perforatum (HP) against DN. Rats were allocated into six groups: control, received normal saline; diabetic untreated (DM), received single dose of streptozotocin (STZ) after injection of nicotinamide (NA); gliclazide, received STZ,NA + gliclazide (10 mg/kg); DM + HP50, DM + HP100, DM + HP200, received STZ,NA and HP 50, 100, 200 mg/kg, respectively. Gliclazide and HP were administered daily via gavage for 8 weeks. Serum glucose, insulin, kidney function and histopathological picture were assessed. Furthermore, oxidative/nitrosative stress, inflammatory cytokines, apoptotic and fibrotic markers were measured. Diabetic untreated group showed increase in serum glucose, urea, creatinine with albuminurea. Renal expression of protein for nuclear factor kappa-B (NF-кB), renal expression of inducible nitric oxide synthase (iNOS), cyclooxygenase II (COXII), collagen IV, fibronectin were elevated. Malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intracellular adhesion molecule (ICAM-1), monocellular chemoattractant protein-1 (MCP-1), tumour growth factor- β (TGF-β), caspase-3 and cytochrome c contents were also increased consequently with decline of serum insulin, expression of peroxisome proliferator-activated receptor (PPARγ), renal reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Treatment with either gliclazide or HP mitigated the deleterious effects of STZ on the tested parameters. These findings indicate for the first time that HP may have a renoprotective effect against DN through reduction of oxidative/nitrosative stress, enhancement of antioxidant defense mechanisms, decline of inflammatory cytokines, antifibrotic, antiapoptotic and blood glucose lowering properties.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Dalia M
authors.identifier: http://orcid.org/0000-0002-4379-6323
authors.initials: DM
authors.lastname: Abd El Motteleb
authors.affiliation: Department of Medical Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Dalia I
authors.initials: DI
authors.lastname: Abd El Aleem
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D024141:Collagen Type IV / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005907:Gliclazide / Q000494:pharmacology; D020902:Hypericum / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000975:Antioxidants; D024141:Collagen Type IV; D005353:Fibronectins; D018836:Inflammation Mediators; D016328:NF-kappa B; D047495:PPAR gamma; D016212:Transforming Growth Factor beta; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D005907:Gliclazide
keywords: 
  hypericum perforatum
  ; NF-кB; PPAR γ; TGF-β; diabetic nephropathy; gliclazide; oxidative stress