PMID- 34925317 OWN - NLM STAT- MEDLINE DCOM- 20220210 LR - 20220210 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus. PG - 733808 LID - 10.3389/fimmu.2021.733808 [doi] LID - 733808 AB - 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 (Lep)db/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-alpha) 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. CI - Copyright (c) 2021 Liu, Zhang, Sheng, Liang, Liu, Moran Guerrero, Lu, Mao, Dai, Liu and Zhang. FAU - Liu, Jialing AU - Liu J AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Nephrology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, China. FAU - Zhang, Yanmei AU - Zhang Y AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Nephrology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Sheng, Hongqin AU - Sheng H AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Nephrology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Liang, Chunling AU - Liang C AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China. FAU - Liu, Huazhen AU - Liu H AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China. FAU - Moran Guerrero, Jose Alberto AU - Moran Guerrero JA AD - Monterrey Institute of Technology, Tecnologico, Monterrey, Mexico. FAU - Lu, Zhaoyu AU - Lu Z AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Nephrology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Mao, Wei AU - Mao W AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Nephrology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Dai, Zhenhua AU - Dai Z AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China. AD - Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Diseases, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Liu, Xusheng AU - Liu X AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Nephrology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zhang, Lei AU - Zhang L AD - State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Nephrology Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Section of Immunology and Joint Immunology Program, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China. AD - Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211203 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Protective Agents) RN - 8O1CR18L82 (hyperoside) RN - 9IKM0I5T1E (Quercetin) SB - IM MH - Animals MH - Cell Polarity/*drug effects MH - Cells, Cultured MH - Diabetes Mellitus, Experimental/*complications MH - Diabetes Mellitus, Type 2/*complications MH - Diabetic Nephropathies/*complications/*drug therapy/immunology MH - Drugs, Chinese Herbal/*administration & dosage MH - Macrophage Activation/*drug effects MH - Macrophages/*immunology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nephritis/*complications/*drug therapy/immunology MH - Phytotherapy/*methods MH - Protective Agents/*administration & dosage MH - Quercetin/administration & dosage/*analogs & derivatives MH - T-Lymphocytes, Regulatory/immunology MH - Th2 Cells/immunology MH - Treatment Outcome PMC - PMC8678409 OTO - NOTNLM OT - Th1 cell OT - Treg cell OT - diabetic nephropathy OT - hyperoside OT - macrophage polarization OT - renal inflammation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/12/21 06:00 MHDA- 2022/02/11 06:00 PMCR- 2021/01/01 CRDT- 2021/12/20 06:06 PHST- 2021/06/30 00:00 [received] PHST- 2021/11/04 00:00 [accepted] PHST- 2021/12/20 06:06 [entrez] PHST- 2021/12/21 06:00 [pubmed] PHST- 2022/02/11 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.733808 [doi] PST - epublish SO - Front Immunol. 2021 Dec 3;12:733808. doi: 10.3389/fimmu.2021.733808. eCollection 2021.