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

作者：Jialing Liu, Yanmei Zhang, Hongqin Sheng, Chun-Ling Liang, Huazhen Liu, Jose A. Moran-Guerrero, Zhaoyu Lu, Wei Mao, Zhenhua Dai, Xusheng Liu, Lei Zhang · 发表于：Frontiers in Immunology · 年份：2021 · DOI：10.3389/fimmu.2021.733808 · 被引用次数：97 · 研究领域：Immune cells in cancer、Adipokines, Inflammation, and Metabolic Diseases、Chronic Kidney Disease and Diabetes

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-α) and indu...