Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome

Abstract Background The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. Naringin exhibits anti-inflammatory and anti-oxidation effects among others, b...

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Main Authors: Fenqin Chen, Guozhu Wei, Jiao Xu, Xiaoyu Ma, Qiuyue Wang
Format: Article
Language:English
Published: BMC 2018-06-01
Series:BMC Complementary and Alternative Medicine
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12906-018-2257-y
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author Fenqin Chen
Guozhu Wei
Jiao Xu
Xiaoyu Ma
Qiuyue Wang
author_facet Fenqin Chen
Guozhu Wei
Jiao Xu
Xiaoyu Ma
Qiuyue Wang
author_sort Fenqin Chen
collection DOAJ
description Abstract Background The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. Naringin exhibits anti-inflammatory and anti-oxidation effects among others, but its specific mechanisms are not clear. We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD). Methods To assess the therapeutic potential of naringin and the mechanisms involved, we cultured rat glomerular mesangial cells and grouped them according to different glucose concentrations, different action times, different concentrations of MCC950, and different concentrations of naringin.The cell proliferation was measured by MTT assay. The expression of Interleukin-1β(IL-1β) and Interleukin18 (IL-18) in the cell supernatant were detected by ELISA. The expression and activity of NLPR3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and Caspase-1 were detected by Western Blot. Results The expressions of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in rat glomerular mesangial cells were significantly higher in the high glucose (HG) group than in the control normal glucose (NG) group and exhibited time-dependence activity. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 in different treatment groups were significantly lower compared with the HG group after 48 h of MCC950 pre-treatment (p < 0.05). Pre-treatment with naringin produced the same results. Naringin also inhibited the proliferation of cells. Conclusions The NLRP3-inflammasome potentially plays a role in the process of activation and inflammation of glomerular mesangial cells as induced by high-glucose conditions. Naringin inhibited the proliferation of cells that were induced by high glucose. Further, it reduced the expression of inflammatory factors that are mediated by NLRP3 through the NLRP3-caspase-1-IL-1β/IL-18 signaling pathway, which makes naringin a potentially novel treatment for DKD disease.
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spelling doaj.art-4daf7c7daad64658858da95e128a46572022-12-22T01:46:11ZengBMCBMC Complementary and Alternative Medicine1472-68822018-06-0118111110.1186/s12906-018-2257-yNaringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 InflammasomeFenqin Chen0Guozhu Wei1Jiao Xu2Xiaoyu Ma3Qiuyue Wang4Departments of Geriatric, the First Affiliated Hospital, China Medical UniversityDepartment of Radiology, Orthopedic Hospital of ShenyangDepartments of Geriatric, the First Affiliated Hospital, China Medical UniversityDepartments of Geriatric, the First Affiliated Hospital, China Medical UniversityDepartments of Endocrinology, the First Affiliated Hospital, China Medical UniversityAbstract Background The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. Naringin exhibits anti-inflammatory and anti-oxidation effects among others, but its specific mechanisms are not clear. We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD). Methods To assess the therapeutic potential of naringin and the mechanisms involved, we cultured rat glomerular mesangial cells and grouped them according to different glucose concentrations, different action times, different concentrations of MCC950, and different concentrations of naringin.The cell proliferation was measured by MTT assay. The expression of Interleukin-1β(IL-1β) and Interleukin18 (IL-18) in the cell supernatant were detected by ELISA. The expression and activity of NLPR3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and Caspase-1 were detected by Western Blot. Results The expressions of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in rat glomerular mesangial cells were significantly higher in the high glucose (HG) group than in the control normal glucose (NG) group and exhibited time-dependence activity. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 in different treatment groups were significantly lower compared with the HG group after 48 h of MCC950 pre-treatment (p < 0.05). Pre-treatment with naringin produced the same results. Naringin also inhibited the proliferation of cells. Conclusions The NLRP3-inflammasome potentially plays a role in the process of activation and inflammation of glomerular mesangial cells as induced by high-glucose conditions. Naringin inhibited the proliferation of cells that were induced by high glucose. Further, it reduced the expression of inflammatory factors that are mediated by NLRP3 through the NLRP3-caspase-1-IL-1β/IL-18 signaling pathway, which makes naringin a potentially novel treatment for DKD disease.http://link.springer.com/article/10.1186/s12906-018-2257-yDiabetes mellitusDiabetic kidney diseaseNLRP3 inflammasomeNLRP3-caspase-1-IL-1β/IL-18 signaling pathwayNaringin
spellingShingle Fenqin Chen
Guozhu Wei
Jiao Xu
Xiaoyu Ma
Qiuyue Wang
Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome
BMC Complementary and Alternative Medicine
Diabetes mellitus
Diabetic kidney disease
NLRP3 inflammasome
NLRP3-caspase-1-IL-1β/IL-18 signaling pathway
Naringin
title Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome
title_full Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome
title_fullStr Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome
title_full_unstemmed Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome
title_short Naringin ameliorates the high glucose-induced rat mesangial cell inflammatory reaction by modulating the NLRP3 Inflammasome
title_sort naringin ameliorates the high glucose induced rat mesangial cell inflammatory reaction by modulating the nlrp3 inflammasome
topic Diabetes mellitus
Diabetic kidney disease
NLRP3 inflammasome
NLRP3-caspase-1-IL-1β/IL-18 signaling pathway
Naringin
url http://link.springer.com/article/10.1186/s12906-018-2257-y
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