Prophylactic effect of baicalein against renal dysfunction in type 2 diabetic rats

Biochimie. 2014 Nov:106:101-10. doi: 10.1016/j.biochi.2014.08.006. Epub 2014 Aug 20.

Abstract

Despite a tremendous advancement in the management of diabetes mellitus, diabetic nephropathy (DN) is still a significant problem for many patients with diabetes, because of the inefficacy and associated side effects of pharmacological drugs. There is a demand for new therapeutic drugs which on one hand efficiently prevent the development of DN by targeting several metabolic and inflammatory pathways, and on the other hand, are side-effect free. In recent years, many researchers have suggested that inflammation plays an important role in the development of DN, hence, NF-κB has received much attention. We investigated the nephroptotective effects of baicalein (BAC), a flavonoid, in high fat diet/streptozotocin induced type 2 diabetic Wistar rats. BAC (10 mg/kg bw/day and 20 mg/kg bw/day) treatment was given to the diabetic rats by oral gavage for 16 weeks post induction of diabetes. The effect of BAC was compared to a commercial antidiabetic drug rosiglitazone (RZ, 3 mg/kg bw/day). BAC and RZ treatment significantly lowered food intake, body weight and levels of fasting blood glucose, HbA1c and homeostasis model assessment index (HOMA-IR) in diabetic rats. Both, BAC and RZ restored normal renal function and mitigated renal oxidative stress. BAC and RZ also suppressed the activation of NF-κB, decreased expression of iNOS and TGF-β1, and ameliorated the structural changes in renal tissues. Moreover, BAC also normalized the levels of serum pro-inflammatory cytokines and liver function enzymes. However, rosiglitazone treatment produced liver toxicity as was evident from increased serum levels of liver function enzymes; ALP, SGOT and SGPT. Taken together, BAC treatment preserved renal function by anti-hyperglycemic, antioxidant and anti-inflammatory effects. Moreover, BAC was found to be more effective as compared to RZ, suggesting the efficacy of BAC in the treatment of DN.

Keywords: Baicalein; Diabetic nephropathy; Insulin resistance; Oxidative stress; Renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alanine Transaminase / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Aspartate Aminotransferases / blood
  • Aspartate Aminotransferases / metabolism
  • Blood Glucose / metabolism
  • Blotting, Western
  • Body Weight / drug effects
  • Cytokines / blood
  • Diabetes Mellitus, Type 2 / chemically induced
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / prevention & control*
  • Diet, High-Fat
  • Eating / drug effects
  • Flavanones / pharmacology*
  • Hypoglycemic Agents / pharmacology
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney / physiopathology
  • Male
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Rats, Wistar
  • Rosiglitazone
  • Streptozocin
  • Thiazolidinediones / pharmacology
  • Transforming Growth Factor beta1 / metabolism
  • Treatment Outcome

Substances

  • Antioxidants
  • Blood Glucose
  • Cytokines
  • Flavanones
  • Hypoglycemic Agents
  • NF-kappa B
  • Thiazolidinediones
  • Transforming Growth Factor beta1
  • Rosiglitazone
  • baicalein
  • Streptozocin
  • Nitric Oxide Synthase Type II
  • Aspartate Aminotransferases
  • Alanine Transaminase