Chrysin Inhibits Advanced Glycation End Products-Induced Kidney Fibrosis in Renal Mesangial Cells and Diabetic Kidneys

• Published in: Nutrients 2018-07, Vol.10 (7), p.882
• Main Authors: Lee, Eun-Jung, Kang, Min-Kyung, Kim, Dong Yeon, Kim, Yun-Ho, Oh, Hyeongjoo, Kang, Young-Hee
• Format: Article
• Language: English
• Subjects: Accumulation; Actin; advanced glycation end products; Advanced glycosylation end products; Animals; bees; Blood Glucose - metabolism; Bovine serum albumin; Cells, Cultured; chrysin; Collagen; Cytoprotection; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetic Nephropathies - etiology; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic Nephropathies - prevention & control; Diabetic nephropathy; Disease Models, Animal; Dose-Response Relationship, Drug; Exposure; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Fibrosis; Flavonoids - pharmacology; Glucose; Glucose - toxicity; glycation; Glycation End Products, Advanced - toxicity; Glycosylation; Growth factors; herbs; Humans; in vitro studies; In vivo methods and tests; in vivo studies; Kidneys; Matrix metalloproteinases; Matrix protein; Mesangial cells; Mesangial Cells - drug effects; Mesangial Cells - metabolism; Mesangial Cells - pathology; metalloproteinases; Mice; Mice, Inbred C57BL; Muscles; Nephropathy; noninsulin-dependent diabetes mellitus; Propolis; protein deposition; Proteins; Receptor for Advanced Glycation End Products - metabolism; Rodents; Serum albumin; Serum Albumin, Bovine - toxicity; Signal Transduction - drug effects; Smad protein; Smad Proteins, Receptor-Regulated - metabolism; Smooth muscle; tissues; Transforming Growth Factor beta - metabolism; transforming growth factor beta 1
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu10070882

Advanced glycation end products (AGEs) play a causative role in the development of diabetic nephropathy via induction of matrix protein deposition in kidneys. This study investigated inhibitory effects of chrysin, present in bee propolis and herbs, on glomerulosclerosis in db/db mice and AGEs-exposed renal mesangial cells. The in vivo study explored the demoting effects of 10 mg/kg chrysin on glomerular fibrosis in a type 2 diabetic model. Oral supplementation of chrysin inhibited the collagen fiber accumulation and α-smooth muscle actin (α-SMA) induction in periodic acid schiff-positive renal tissues of db/db mice. Moreover, treating db/db mice with chrysin diminished the level of AGEs increased in diabetic glomeruli. The in vitro study employed human mesangial cells exposed to 100 μg/mL AGE-BSA for 72 h in the presence of 1⁻20 μM chrysin. Glucose increased mesangial AGE production via induction of receptor for AGEs. Chrysin suppressed the induction of collagens, α-SMA, fibroblast-specific protein-1 and matrix metalloproteinases enhanced by AGE-bovine serum albumin. Furthermore, chrysin blunted transforming growth factor-β1 induction and Smad 2/3 activation in AGEs-exposed mesangial cells. These results demonstrate that chrysin attenuated accumulation of myofibroblast-like cells and matrix proteins in AGEs-laden diabetic glomeruli. Therefore, chrysin may be a potential renoprotective agent targeting glucose-mediated AGEs-associated glomerulosclerosis and fibrosis.