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Evidence-Based Complementary and Alternative Medicine
Volume 2019, Article ID 4509403, 12 pages
Research Article

Protective Effects of Broussonetia kazinoki Siebold Fruit Extract against Palmitate-Induced Lipotoxicity in Mesangial Cells

1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea
2College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea
3Gachon Medical and Convergence Institute, Gachon Gil Medical Center, Incheon 21565, Republic of Korea

Correspondence should be addressed to Hee-Sook Jun;

Received 27 September 2018; Revised 19 December 2018; Accepted 25 December 2018; Published 8 January 2019

Academic Editor: Jian-Li Gao

Copyright © 2019 Donghee Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Diabetic nephropathy is one of the most serious complications of diabetes. Lipotoxicity in glomerular mesangial cells is associated with the progression of diabetic nephropathy. Paper mulberry, Broussonetia kazinoki Siebold (BK), has been used in oriental medicine for human health problems. However, to date, the beneficial effect of BK fruit has not been studied. In this study, we investigated the protective effect of an ethanolic extract of BK fruit (BKFE) against palmitate- (PA-) induced toxicity in mesangial cells. BKFE significantly increased the viability of PA-treated SV40 MES13 cells. BKFE significantly inhibited PA-induced apoptosis and decreased the expression of apoptotic genes, cleaved caspase-3, and cleaved PARP. Moreover, BKFE inhibited the expression of endoplasmic reticulum (ER) stress-related genes, such as BiP, phosphorylated eIF2α, cleaved ATF6, and spliced XBP-1, in PA-treated SV40 MES13 cells. BKFE decreased PA-induced ROS production. In addition, BKFE activated the transcription factor Nrf2 and increased the expression of antioxidant enzymes. However, knockdown of Nrf2 using siRNA suppressed this BKFE-induced increase in antioxidant enzyme expression. Furthermore, the protective effect of BKFE on PA-induced apoptosis was significantly reduced by Nrf2 knockdown. In conclusion, BKFE induced the expression of antioxidant enzymes via activation of Nrf2 and protected against PA-induced lipotoxicity in mesangial cells.