<i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia. The chronic hyperglycemic condition causes hyperinflammation via activation of nucleotide-binding oligomerization domain-like pyrin domain containing receptor 3 (NLRP3) inflammasome and abnormally leads t...

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Main Authors: Ji Eun Park, Heaji Lee, Sun Yeou Kim, Yunsook Lim
Format: Article
Language:English
Published: MDPI AG 2020-02-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/9/2/148
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author Ji Eun Park
Heaji Lee
Sun Yeou Kim
Yunsook Lim
author_facet Ji Eun Park
Heaji Lee
Sun Yeou Kim
Yunsook Lim
author_sort Ji Eun Park
collection DOAJ
description Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia. The chronic hyperglycemic condition causes hyperinflammation via activation of nucleotide-binding oligomerization domain-like pyrin domain containing receptor 3 (NLRP3) inflammasome and abnormally leads to morphological and functional changes in kidney. A previous study showed a protective effect of <i>Lespedeza bicolor</i> extract (LBE) on endothelial dysfunction induced by methylglyoxal glucotoxicity. We aimed to investigate whether LBE ameliorated renal damage through regulation of NLRP3 inflammasome-dependent hyper-inflammation in T2DM mice. After T2DM induction by a high fat diet and low dose of streptozotocin (30 mg/kg), the mice were administered with different dosages of LBE (100 or 250 mg/kg/day) by gavage for 12 weeks. LBE supplementation ameliorated kidney dysfunction demonstrated by urine albumin-creatinine at a low dose and plasma creatinine, blood urea nitrogen (BUN), and glomerular hypertrophy at a high dose. Furthermore, a high dose of LBE supplementation significantly attenuated renal hyper-inflammation associated with NLRP3 inflammasome and oxidative stress related to nuclear factor erythroid 2-related factor 2 (Nrf-2) in T2DM mice. Meanwhile, a low dose of LBE supplementation up-regulated energy metabolism demonstrated by phosphorylation of adenosine monophosphate kinase (AMPK) and Sirtuin (SIRT)-1 in T2DM mice. In conclusion, the current study suggested that LBE, in particular, at a high dose could be used as a beneficial therapeutic for hyperglycemia-induced renal damage in T2DM.
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spelling doaj.art-663d70b072d0478f8e4d7ba268feaacf2023-06-02T00:01:45ZengMDPI AGAntioxidants2076-39212020-02-019214810.3390/antiox9020148antiox9020148<i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic MiceJi Eun Park0Heaji Lee1Sun Yeou Kim2Yunsook Lim3Department of Food and Nutrition, Kyung Hee Univerity, 26 Kyung Hee-Daero, Dongdamun-Gu, Seoul 02447, KoreaDepartment of Food and Nutrition, Kyung Hee Univerity, 26 Kyung Hee-Daero, Dongdamun-Gu, Seoul 02447, KoreaGachon Institute of Pharmaceutical Science, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaDepartment of Food and Nutrition, Kyung Hee Univerity, 26 Kyung Hee-Daero, Dongdamun-Gu, Seoul 02447, KoreaType 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia. The chronic hyperglycemic condition causes hyperinflammation via activation of nucleotide-binding oligomerization domain-like pyrin domain containing receptor 3 (NLRP3) inflammasome and abnormally leads to morphological and functional changes in kidney. A previous study showed a protective effect of <i>Lespedeza bicolor</i> extract (LBE) on endothelial dysfunction induced by methylglyoxal glucotoxicity. We aimed to investigate whether LBE ameliorated renal damage through regulation of NLRP3 inflammasome-dependent hyper-inflammation in T2DM mice. After T2DM induction by a high fat diet and low dose of streptozotocin (30 mg/kg), the mice were administered with different dosages of LBE (100 or 250 mg/kg/day) by gavage for 12 weeks. LBE supplementation ameliorated kidney dysfunction demonstrated by urine albumin-creatinine at a low dose and plasma creatinine, blood urea nitrogen (BUN), and glomerular hypertrophy at a high dose. Furthermore, a high dose of LBE supplementation significantly attenuated renal hyper-inflammation associated with NLRP3 inflammasome and oxidative stress related to nuclear factor erythroid 2-related factor 2 (Nrf-2) in T2DM mice. Meanwhile, a low dose of LBE supplementation up-regulated energy metabolism demonstrated by phosphorylation of adenosine monophosphate kinase (AMPK) and Sirtuin (SIRT)-1 in T2DM mice. In conclusion, the current study suggested that LBE, in particular, at a high dose could be used as a beneficial therapeutic for hyperglycemia-induced renal damage in T2DM.https://www.mdpi.com/2076-3921/9/2/148<i>lespedeza bicolor</i>type 2 diabetesrenal inflammationnlrp3 inflammasomeenergy metabolismoxidative stress
spellingShingle Ji Eun Park
Heaji Lee
Sun Yeou Kim
Yunsook Lim
<i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice
Antioxidants
<i>lespedeza bicolor</i>
type 2 diabetes
renal inflammation
nlrp3 inflammasome
energy metabolism
oxidative stress
title <i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice
title_full <i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice
title_fullStr <i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice
title_full_unstemmed <i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice
title_short <i>Lespedeza bicolor</i> Extract Ameliorated Renal Inflammation by Regulation of NLRP3 Inflammasome-Associated Hyperinflammation in Type 2 Diabetic Mice
title_sort i lespedeza bicolor i extract ameliorated renal inflammation by regulation of nlrp3 inflammasome associated hyperinflammation in type 2 diabetic mice
topic <i>lespedeza bicolor</i>
type 2 diabetes
renal inflammation
nlrp3 inflammasome
energy metabolism
oxidative stress
url https://www.mdpi.com/2076-3921/9/2/148
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