Baicalin and chrysin mixture imparts cyto-protection against methylglyoxal induced cytotoxicity and diabetic tubular injury by modulating RAGE, oxidative stress and inflammation

Environ Toxicol Pharmacol. 2017 Mar:50:67-75. doi: 10.1016/j.etap.2017.01.013. Epub 2017 Jan 23.

Abstract

Protective effect of mixture of flavonoids baicalin and chrysin (BCH) was studied against methylglyoxal (MG, a precursor of AGEs) induced cytotoxicity in NRK 52E kidney epithelial cells. Flow cytometry and microscopic analysis showed increased ROS generation, compromised antioxidant status, depolarization of mitochondria and apoptosis in MG stressed cells which were significantly transformed (p≤0.01) during BCH co-treatment. In vivo studies in streptozotocin induced diabetic rats increased protein levels of iNOS, protein kinase C (PKC) and decreased IκB which was modulated by oral BCH treatment (75mg baicalin and 10mg chrysin/kg b.wt.). Increased levels of AGEs and their receptor proteins (RAGE) in diabetic rats were reduced significantly (p≤0.01) in BCH treated group. Renal tubular injuries and deranged kidney function were significantly improved in BCH treated animals. The results indicate that the protection accorded by BCH through its antioxidant and anti-inflammatory effects can be explored for management of diabetic nephropathy.

Keywords: Advanced glycation end products; Baicalin; Chrysin; Diabetic nephropathy; Methylglyoxal; Oroxylum indicum.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications*
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / metabolism
  • Drug Therapy, Combination
  • Epithelial Cells / drug effects
  • Flavonoids / administration & dosage*
  • Flavonoids / pharmacology
  • Glycation End Products, Advanced / analysis
  • Male
  • Mitochondria / drug effects
  • Oxidative Stress / drug effects*
  • Pyruvaldehyde / toxicity*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Streptozocin

Substances

  • Flavonoids
  • Glycation End Products, Advanced
  • Reactive Oxygen Species
  • baicalin
  • chrysin
  • Streptozocin
  • Pyruvaldehyde