Madduma Hewage Susara, Prashar Suvira, Debnath Samir C, O Karmin, Siow Yaw L
Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.
Department of Physiology & Pathophysiology, University of Manitoba, Winnipeg, MB, Canada.
Front Med (Lausanne). 2020 Mar 27;7:80. doi: 10.3389/fmed.2020.00080. eCollection 2020.
Chronic low-grade inflammation is a major stimulus for progression of chronic kidney disease (CKD) in individuals consuming high-fat diet. Currently, there are limited treatment options for CKD other than controlling the progression rate and its associated complications. Lingonberry ( L.) is rich in anthocyanins with demonstrated anti-inflammatory effect. In the current study, we investigated the potential renal protective effect of lingonberry and its anthocyanin (cyanidin-3-glucoside) in high-fat diet fed obese mice and in human proximal tubular cells. Prolonged consumption of high-fat diets is strongly associated with obesity, abnormal lipid and glucose metabolism. Mice (C57BL/6J) fed a high-fat diet (62% kcal fat) for 12 weeks developed renal injury as indicated by an elevation of blood urea nitrogen (BUN) level as well as an increase in renal kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and renin expression. Those mice displayed an activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and increased expression of inflammatory cytokines-monocyte chemoattractant-1 (MCP-1), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) in the kidneys. Mice fed a high-fat diet also had a significant elevation of inflammatory cytokine levels in the plasma. Dietary supplementation of lingonberry for 12 weeks not only attenuated high-fat diet-induced renal inflammatory response but also reduced kidney injury. Such a treatment improved plasma lipid and glucose profiles, reduced plasma inflammatory cytokine levels but did not affect body weight gain induced by high-fat diet feeding. Lingonberry extract or its active component cyanidin-3-glucoside effectively inhibited palmitic acid-induced NF-κB activation and inflammatory cytokine expression in proximal tubular cells. These results suggest that lingonberry supplementation can reduce inflammatory response and prevent chronic kidney injury. Such a renal protective effect by lingonberry and its active component may be mediated, in part, through NF-κB signaling pathway.
慢性低度炎症是食用高脂饮食个体慢性肾脏病（CKD）进展的主要刺激因素。目前，除了控制疾病进展速度及其相关并发症外，CKD的治疗选择有限。越橘富含花青素，具有抗炎作用。在本研究中，我们调查了越橘及其花青素（矢车菊素-3-葡萄糖苷）对高脂饮食喂养的肥胖小鼠和人近端肾小管细胞的潜在肾脏保护作用。长期食用高脂饮食与肥胖、脂质和葡萄糖代谢异常密切相关。喂食高脂饮食（62%千卡脂肪）12周的小鼠（C57BL/6J）出现肾损伤，表现为血尿素氮（BUN）水平升高以及肾损伤分子-1（KIM-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和肾素表达增加。这些小鼠表现出活化B细胞核因子κB（NF-κB）的激活以及肾脏中炎性细胞因子单核细胞趋化蛋白-１（MCP-1）、肿瘤坏死因子α（TNF-α）、白细胞介素-6（IL-6）表达增加。喂食高脂饮食的小鼠血浆中的炎性细胞因子水平也显著升高。饮食中补充越橘12周不仅减轻了高脂饮食诱导的肾脏炎症反应，还减轻了肾脏损伤。这种治疗改善了血浆脂质和葡萄糖谱，降低了血浆炎性细胞因子水平，但不影响高脂饮食喂养引起的体重增加。越橘提取物或其活性成分矢车菊素-3-葡萄糖苷有效抑制棕榈酸诱导的近端肾小管细胞中NF-κB激活和炎性细胞因子表达。这些结果表明，补充越橘可以减轻炎症反应并预防慢性肾损伤。越橘及其活性成分的这种肾脏保护作用可能部分通过NF-κB信号通路介导。
