Dong Yeon Kim, Min-Kyung Kang, Eun-Jung Lee, Yun-Ho Kim, Hyeongjoo Oh, and Young-Hee Kang^*

Department of Food Science and Nutrition, Hallym University, Chuncheon, Kangwon-do 24252, Korea

^*To whom correspondence should be addressed.

Abstract
1 Scope
The maintenance of interpodocyte slit diaphragm is critical in the sieving function of glomerular filtration barrier. Eucalyptol is a natural constituent in aromatic plants with antioxidant properties. This study investigates whether and how eucalyptol inhibits podocyte slit diaphragm malfunction in glucose-exposed podocytes and diabetic mouse kidneys.

2 Methods and results
Podocytes were incubated in media containing 33 mm glucose with 1-20 μm eucalyptol. The in vivo model employed db/db mice orally administrated with 10 mg kg-1 eucalyptol. Nontoxic eucalyptol enhanced podocyte expression of nephrin, podocin, FAT-1, CD2AP, and α-actinin-4 diminished by glucose. Oral administration of eucalyptol augmented the induction of the slit diaphragm proteins, α-actinin-4, and integrin β1 in diabetic kidneys, and ameliorated glomerular fibrosis and foot process effacement. Eucalyptol counteracted the receptor of advanced glycation end products (RAGE) induction in podocytes with glucose or AGE-BSA, and elevated the reduction of the slit diaphragm proteins by AGE-BSA. Eucalyptol attenuated the RAGE induction and AGE accumulation in diabetic kidneys. The blockade of ERK-c-Myc signaling enhanced the nephrin and CD2AP expression downregulated in AGE-exposed podocytes. These results indicate that eucalyptol blocked glucose-induced AGE-RAGE axis and podocyte injury through disturbing RAGE-ERK-c-Myc signaling.

3 Conclusion
Eucalyptol may be a potent agent antagonizing diabetes-associated malformation of interpodocyte slit junction and podocyte actin cytoskeleton.