Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 316

P08-058 - Chrysin blocks advanced glycation end products-associated glomerulosclerosis by suppressing autophagy in mesangial cells and db/db mice

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Diabetic nephropathy (DN) is one of the major diabetic complications and the leading cause of end-stage renal diseases. Advanced glycation end products (AGEs) play a causative role in the development of DN via induction of extracellular matrix accumulation. Recent research has demonstrated that autophagy is involved in the development of DN. The aim of this study was to explore the involvement of autophagy and mechanistic actions of chrysin in AGEs-exposed mesangial fibrogenesis.


Methods: The in vitro study incubated human mesangial cells exposed to 33 mM glucose and 100 μg/ml AGEs-BSA for 3 d in the absence and presence of 1-20 μM chrysin (5, 7-dihydroxyflavone) present in bee propolis and herbs. The in vivo study employed type 2 diabetic db/db mice orally administrated for 10 weeks with 10 mg/kg chrysin.


Results: Chrysin attenuated the formation of the stress fiber F-actin in 33 mM glucose- or AGEs-BSA exposed mesangial cells. Chrysin suppressed the induction of microtubule-associated proteins 1A/1B light chain 3B (LC3), beclin-1, and autophagocytosis-associated proteins of Atg3 and Atg7 enhanced by AGEs-exposed in mesangial cells. In addition, chrysin inhibited the mesangial induction of phosphorylated mechanistic target of rapamycin (p-mTOR) by AGEs. Oral supplementation of 10 mg/kg chrysin encumbered the induction of p-mTOR in db/db mouse glomeruli. Moreover, treating db/db mice with chrysin diminished the autophagy enhanced in diabetic glomeruli.


Conclusion: These results demonstrate that chrysin attenuated AGEs-induced mesangial fibrogenesis via mTOR signal-mediated inhibition of autophagy. These findings suggest the possibility that chrysin could be a potential agent for the treatment of diabetic glomerulosclerosis.


CoAuthors: young-hee kang – HALLYM UNIVERSITY

Eun-Jung Lee

student
HALLYM UNIVERSITY
Chuncheon-si, Kangwon-do, Republic of Korea