<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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MDPI AG
2020-02-01
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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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