An anti-inflammatory chalcone derivative prevents heart and kidney from hyperlipidemia-induced injuries by attenuating inflammation
An anti-inflammatory chalcone derivative prevents heart and kidney from hyperlipidemia-induced injuries by attenuating inflammation
复制标题
抗炎查耳酮衍生物可通过减轻炎症来防止心脏和肾脏因高脂血症引起的损伤
DOI：
10.1016/j.taap.2017.11.003
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发表时间：
2018-01-01
影响因子：
3.8
通讯作者：
Liang, Guang
中科院分区：
文献类型：
--
作者：
Chen, Xiong;Yu, Weihui;Liang, Guang
肥胖症在发达国家和发展中国家都是一种日益严重的流行病。肥胖中的脂质过载产生慢性、低度炎症状态。心脏和肾脏组织中的炎症增加已被证明会促进肥胖症患者心脏和肾脏损伤的进展。以前，我们发现一种新的查耳酮衍生物，L 6 H21，抑制脂多糖诱导的炎症反应。在本研究中，我们研究了L 6 H21对炎症反应的影响，在文化和动物模型的脂质过载。我们利用棕榈酸（PA）在小鼠腹腔巨噬细胞和高脂饮食（HFD）喂养的载脂蛋白E敲除（ApoE（-/-））小鼠中进行攻击，以研究L 6 H21是否减轻炎症反应。我们的研究表明，L 6 H21通过抑制丝裂原活化蛋白激酶（MAPK）和核因子-κ B（NF-κ B）信号通路，显著降低PA诱导的巨噬细胞炎性细胞因子的表达。L 6 H21还减少了肾脏和心脏组织中的纤维化，以及喂食HFD的ApoE-/-小鼠中的炎症反应指数。这些体内效应也与L 6 H21对MAPK和NF κ B信号传导的抑制有关。这些发现强烈提示L 6 H21可能是高脂饮食诱导的心脏和肾脏损伤的潜在因子。
Obesity is a growing pandemic in both developed and developing countries. Lipid overload in obesity generates a chronic, low-grade inflammation state. Increased inflammation in heart and renal tissues has been shown to promote the progression of heart and renal damage in obesity. Previously, we found that a novel chalcone derivative, L6H21, inhibited lipopolysaccharide-induced inflammatory response. In the present study, we investigated the effects of L6H21 on inflammatory responses in culture and in animal models of lipid overload. We utilized palmitic acid (PA) challenging in mouse peritoneal macrophages and apolipoprotein E knockout (ApoE(-/-)) mice fed a high fat diet (HFD) to study whether L6H21 mitigates the inflammatory response. Our studies show that L6H21 significantly reduced PA-induced expression of inflammatory cytokines in macrophages by inhibiting mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF kappa B) signaling pathways. L6H21 also reduced fibrosis in the kidney and heart tissues, and indices of inflammatory response in the ApoE-/- mice fed a HFD. These effects in vivo were also associated with inhibition of MAPK and NF kappa B signaling by L6H21. These findings strongly suggest that L6H21 may be a potential agent for high fat diet-induced injuries in heart and kidney.