{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:07:25Z","timestamp":1793412445954,"version":"4.5.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T00:00:00Z","timestamp":1638489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    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\n                    <jats:sup>Lep<\/jats:sup>\n                    <jats:italic>db\/db<\/jats:italic>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    CD86\n                    <jats:sup>+<\/jats:sup>\n                    ) to anti-inflammatory M2 ones (F4\/80\n                    <jats:sup>+<\/jats:sup>\n                    CD11b\n                    <jats:sup>+<\/jats:sup>\n                    CD206\n                    <jats:sup>+<\/jats:sup>\n                    )\n                    <jats:italic>in vivo<\/jats:italic>\n                    and in bone marrow-derived macrophages (BMDMs)\n                    <jats:italic>in vitro<\/jats:italic>\n                    , 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-\u03b1) 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\n                    <jats:sup>+<\/jats:sup>\n                    T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells while promoting their differentiation into CD4\n                    <jats:sup>+<\/jats:sup>\n                    IL-4\n                    <jats:sup>+<\/jats:sup>\n                    Th2 and CD4\n                    <jats:sup>+<\/jats:sup>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN\n                    <jats:italic>via<\/jats:italic>\n                    promoting macrophage polarization from an M1 to M2 phenotype and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.733808","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T01:21:44Z","timestamp":1638494504000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":106,"title":["Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus"],"prefix":"10.3389","volume":"12","author":[{"given":"Jialing","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqin","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huazhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Alberto","family":"Moran Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xusheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1991.308","article-title":"Possible Role of Tumor Necrosis Factor and Interleukin-1 in the Development of Diabetic 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