A Combination of Geniposide and Chlorogenic Acid Combination Ameliorates Nonalcoholic Steatohepatitis in Mice by Inhibiting Kupffer Cell Activation.

A Combination of Geniposide and Chlorogenic Acid Combination Ameliorates Nonalcoholic Steatohepatitis in Mice by Inhibiting Kupffer Cell Activation.
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DOI:
10.1155/2021/6615881
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发表时间:
2021
影响因子:
--
通讯作者:
Feng Q
Feng Q
中科院分区:
生物学3区
文献类型:
--
作者:
Xin X;Jin Y;Wang X;Cai B;An Z;Hu YY;Feng Q

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非酒精性脂肪性肝炎(NASH)的发病率在全球范围内不断增加。库普弗细胞(KCs)的活化是饮食诱导的NASH发展的核心。我们研究了两种活性化学成分京尼平苷和绿原酸(GC)以特定比例(67:1)的组合是否改善饮食诱导的NASH以及所涉及的潜在机制。研究了暴露于含有胆固醇、胆碱和高糖饮用水的高脂肪和高胆固醇(HFHC)饮食以及用脂多糖(LPS)刺激的RAW 264.7细胞的C57 BL/6 J小鼠。该组合对HFHC诱导的小鼠NASH具有治疗作用。同时发现GC可降低肝巨噬细胞分泌的细胞因子的表达,包括肿瘤坏死因子-α(TNF-α)、白细胞介素-1 α(IL-1α)、IL-1β、IL-6、单核细胞趋化蛋白1(MCP-1)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)。此外,GC减少表达F4/80的KC的数量。GC处理后,RAW264.7细胞TNF-α、诱导型一氧化氮合酶(INOS)、IL-1β、IL-6 mRNA和TNF-α蛋白表达水平均受到抑制。我们的研究结果表明,GC在NASH中具有强烈的抗炎作用,这种作用可以归因于抑制肝脏中的KC活性。
The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide. Activation of Kupffer cells (KCs) is central to the development of diet-induced NASH. We investigated whether a combination of two active chemical components, geniposide and chlorogenic acid (GC), at a specific ratio (67 : 1), ameliorates diet-induced NASH and the underlying mechanisms involved. C57BL/6J mice exposed to a high-fat and high-cholesterol (HFHC) diet containing cholesterol, choline, and high-sugar drinking water, as well as RAW264.7 cells stimulated with lipopolysaccharide (LPS) were studied. The combination exerted a therapeutic effect on HFHC-induced NASH in mice. Simultaneously, GC was found to reduce the expression of cytokines secreted by hepatic macrophages, including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, GC reduced the number of KCs expressing F4/80. Furthermore, TNF-α, inducible nitric oxide synthase (INOS), IL-1β, and IL-6 mRNA and TNF-α protein expression levels were suppressed upon GC treatment in RAW264.7 cells. Our findings suggest that GC has a strong anti-inflammatory effect in NASH, and this effect can be attributed to the suppression of KC activity in the liver.
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