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J Clin Med. 2019 Jul 31;8(8). pii: E1138. doi: 10.3390/jcm8081138.

Therapeutic Potential of Lespedeza bicolor to Prevent Methylglyoxal-Induced Glucotoxicity in Familiar Diabetic Nephropathy.

Author information

1
College of Pharmacy, Gachon University, 191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea.
2
Division of Functional Food Research, Korea Food Research Institute, 245 Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea.
3
College of Pharmacy, Gachon University, 191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. amnaparvin@gmail.com.
4
College of Pharmacy, Gachon University, 191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. sunnykim@gachon.ac.kr.
5
Gachon Institute of Pharmaceutical Science, Gachon University, 191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea. sunnykim@gachon.ac.kr.

Abstract

Lespedeza bicolor (LB) is often used in traditional medicine to remove toxins, replenish energy stores, and regulate various symptoms of diabetes. This study aimed to explore the use of LB as a therapeutic to prevent diabetic nephropathy in methylglyoxal (MGO)-treated models in vitro and in vivo. Western blotting, immunostaining, and biochemical assays were used to obtain several experimental readouts in renal epithelial cells (LLC-PK1) and BALB/c mice. These include: production of reactive oxygen species (ROS), formation of advanced glycation end-products (AGEs), expression of receptor for advanced glycation end-products (RAGE), apoptotic cell death, glucose levels, fatty acid and triglyceride levels, expression of pro-inflammatory cytokines IL-1β and TNF-α, glyoxalase 1 (Glo1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with LB significantly reduced MGO-induced cellular apoptosis, intracellular production of ROS, and formation of AGEs to ameliorate renal dysfunction in vitro and in vivo. Interestingly, administering LB in MGO-treated cells and mice upregulated the expression of Nrf2 and Glo1, and downregulated the expression of IL-1β and TNF-α. Moreover, LB reduced MGO-induced AGE accumulation and RAGE expression in the kidneys, which subsequently reduced AGE-RAGE interactions. Overall, LB ameliorates renal cell apoptosis and corrects renal dysfunction in MGO-treated mice. These findings extend our understanding of the pathogenic mechanism of MGO-induced nephrotoxicity and regulation of the AGE/RAGE axis by Lespedeza bicolor.

KEYWORDS:

Lespedeza bicolor; advanced glycation end-products; diabetic nephropathy; hyperglycemia; methylglyoxal

PMID:
31370192
DOI:
10.3390/jcm8081138
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