Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus

Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a v...

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Autores principales:	Jialing Liu, Yanmei Zhang, Hongqin Sheng, Chunling Liang, Huazhen Liu, Jose Alberto Moran Guerrero, Zhaoyu Lu, Wei Mao, Zhenhua Dai, Xusheng Liu, Lei Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	diabetic nephropathy macrophage polarization hyperoside renal inflammation Th1 cell Treg cell Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/75e498ac37674d5eb4c19a6e3c4d4d39
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spelling	oai:doaj.org-article:75e498ac37674d5eb4c19a6e3c4d4d392021-12-03T06:21:27ZHyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus1664-322410.3389/fimmu.2021.733808https://doaj.org/article/75e498ac37674d5eb4c19a6e3c4d4d392021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.733808/fullhttps://doaj.org/toc/1664-3224Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a variety of pharmacological effects, including anti-oxidative and anti-apoptotic activities as well as podocyte-protective effects, its underlying anti-inflammatory mechanisms remain unclear. Herein, we investigated the therapeutic effects of HPS on murine DN and the potential mechanisms responsible for its efficacy. We used C57BLKS/6J Lepdb/db mice and a high glucose (HG)-induced bone marrow-derived macrophage (BMDM) polarization system to investigate the potentially protective effects of HPS on DN. Our results showed that HPS markedly reduced diabetes-induced albuminuria and glomerular mesangial matrix expansion, accompanied with a significant improvement of fasting blood glucose level, hyperlipidaemia and body weight. Mechanistically, pretreatment with HPS effectively regulated macrophage polarization by shifting proinflammatory M1 macrophages (F4/80+CD11b+CD86+) to anti-inflammatory M2 ones (F4/80+CD11b+CD206+) in vivo and in bone marrow-derived macrophages (BMDMs) in vitro, resulting in the inhibition of renal proinflammatory macrophage infiltration and the reduction in expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) while increasing expression of anti-inflammatory cytokine Arg-1 and CD163/CD206 surface molecules. Unexpectedly, pretreatment with HPS suppressed CD4+ T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4+ T cells while promoting their differentiation into CD4+IL-4+ Th2 and CD4+Foxp3+ Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN via promoting macrophage polarization from an M1 to M2 phenotype and CD4+ T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic.Jialing LiuJialing LiuJialing LiuYanmei ZhangYanmei ZhangHongqin ShengHongqin ShengChunling LiangChunling LiangHuazhen LiuHuazhen LiuJose Alberto Moran GuerreroZhaoyu LuZhaoyu LuWei MaoWei MaoZhenhua DaiZhenhua DaiZhenhua DaiZhenhua DaiXusheng LiuXusheng LiuLei ZhangLei ZhangLei ZhangLei ZhangFrontiers Media S.A.articlediabetic nephropathymacrophage polarizationhyperosiderenal inflammationTh1 cellTreg cellImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic nephropathy macrophage polarization hyperoside renal inflammation Th1 cell Treg cell Immunologic diseases. Allergy RC581-607
spellingShingle	diabetic nephropathy macrophage polarization hyperoside renal inflammation Th1 cell Treg cell Immunologic diseases. Allergy RC581-607 Jialing Liu Jialing Liu Jialing Liu Yanmei Zhang Yanmei Zhang Hongqin Sheng Hongqin Sheng Chunling Liang Chunling Liang Huazhen Liu Huazhen Liu Jose Alberto Moran Guerrero Zhaoyu Lu Zhaoyu Lu Wei Mao Wei Mao Zhenhua Dai Zhenhua Dai Zhenhua Dai Zhenhua Dai Xusheng Liu Xusheng Liu Lei Zhang Lei Zhang Lei Zhang Lei Zhang Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus
description	Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a variety of pharmacological effects, including anti-oxidative and anti-apoptotic activities as well as podocyte-protective effects, its underlying anti-inflammatory mechanisms remain unclear. Herein, we investigated the therapeutic effects of HPS on murine DN and the potential mechanisms responsible for its efficacy. We used C57BLKS/6J Lepdb/db mice and a high glucose (HG)-induced bone marrow-derived macrophage (BMDM) polarization system to investigate the potentially protective effects of HPS on DN. Our results showed that HPS markedly reduced diabetes-induced albuminuria and glomerular mesangial matrix expansion, accompanied with a significant improvement of fasting blood glucose level, hyperlipidaemia and body weight. Mechanistically, pretreatment with HPS effectively regulated macrophage polarization by shifting proinflammatory M1 macrophages (F4/80+CD11b+CD86+) to anti-inflammatory M2 ones (F4/80+CD11b+CD206+) in vivo and in bone marrow-derived macrophages (BMDMs) in vitro, resulting in the inhibition of renal proinflammatory macrophage infiltration and the reduction in expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) while increasing expression of anti-inflammatory cytokine Arg-1 and CD163/CD206 surface molecules. Unexpectedly, pretreatment with HPS suppressed CD4+ T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4+ T cells while promoting their differentiation into CD4+IL-4+ Th2 and CD4+Foxp3+ Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN via promoting macrophage polarization from an M1 to M2 phenotype and CD4+ T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic.
format	article
author	Jialing Liu Jialing Liu Jialing Liu Yanmei Zhang Yanmei Zhang Hongqin Sheng Hongqin Sheng Chunling Liang Chunling Liang Huazhen Liu Huazhen Liu Jose Alberto Moran Guerrero Zhaoyu Lu Zhaoyu Lu Wei Mao Wei Mao Zhenhua Dai Zhenhua Dai Zhenhua Dai Zhenhua Dai Xusheng Liu Xusheng Liu Lei Zhang Lei Zhang Lei Zhang Lei Zhang
author_facet	Jialing Liu Jialing Liu Jialing Liu Yanmei Zhang Yanmei Zhang Hongqin Sheng Hongqin Sheng Chunling Liang Chunling Liang Huazhen Liu Huazhen Liu Jose Alberto Moran Guerrero Zhaoyu Lu Zhaoyu Lu Wei Mao Wei Mao Zhenhua Dai Zhenhua Dai Zhenhua Dai Zhenhua Dai Xusheng Liu Xusheng Liu Lei Zhang Lei Zhang Lei Zhang Lei Zhang
author_sort	Jialing Liu
title	Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus
title_short	Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus
title_full	Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus
title_fullStr	Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus
title_full_unstemmed	Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus
title_sort	hyperoside suppresses renal inflammation by regulating macrophage polarization in mice with type 2 diabetes mellitus
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/75e498ac37674d5eb4c19a6e3c4d4d39
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Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus

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