1,3,6,7-Tetrahydroxy-8-prenylxanthone ameliorates inflammatory responses resulting from the paracrine interaction of adipocytes and macrophages
1,3,6,7-Tetrahydroxy-8-prenylxanthone ameliorates inflammatory responses resulting from the paracrine interaction of adipocytes and macrophages
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DOI：
10.1111/bph.14162
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发表时间：
2018-05-01
影响因子：
7.3
通讯作者：
Lin, Ligen
中科院分区：
文献类型：
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作者：
Li, Dan;Liu, Qianyu;Lin, Ligen
背景和目的脂肪组织的慢性炎症在胰岛素抵抗和2型糖尿病的发生和发展中起关键作用。巨噬细胞对脂肪组织的侵袭和促炎极化在脂肪组织炎症中起着关键作用。山竹(Garcinia Mangostana)的果壳在传统医学中用于治疗各种炎症性疾病。然而，它在调节脂肪组织炎症中的作用尚不清楚。本研究旨在鉴定山竹中具有抗脂肪组织炎症作用的口山梨酮类化合物。采用Western blotting、免疫荧光、实时定量聚合酶链式反应或酶联免疫吸附试验等方法研究山竹中诱导型一氧化氮合酶、细胞因子、趋化因子以及核因子-kappaB和丝裂原活化蛋白激酶途径的组成成分的表达。用Transwell体外实验检测巨噬细胞向脂肪细胞的迁移。采用脂多糖(LPS)诱导的小鼠急性炎症模型，观察了1，3，6，7-四羟基-8-戊烯基口山酮(TPX)对活体脂肪组织炎症反应的影响。结果从山竹中分离得到一系列口山梨酮类化合物，TPX对脂多糖诱导的RAW264.7巨噬细胞产生NO和分泌IL-6有明显的抑制作用。TPX通过抑制MAPKs和NF-kappaB的激活，促进sirtuin 3的表达，从而减轻脂多糖诱导的RAW264.7巨噬细胞的炎症反应，减轻肿瘤坏死因子-α对3T3-L1脂肪细胞的炎症反应。TPX还可阻断RAW264.7巨噬细胞向3T3-L1脂肪细胞的迁移。此外，TPX通过减少促炎细胞因子和阻止巨噬细胞的促炎极化来减轻体内脂肪组织的炎症反应。结论和实施本研究结果表明，TPX破坏了巨噬细胞和脂肪细胞之间的炎症反应，减轻了脂肪组织的炎症反应。
BACKGROUND AND PURPOSEChronic inflammation in adipose tissue is critical in the onset and development of insulin resistance and type 2 diabetes. Macrophage infiltration into adipose tissue and pro-inflammatory polarization play key roles in adipose tissue inflammation. The fruit hull of mangosteen (Garcinia mangostana) is used in traditional medicine to treat various inflammatory diseases. However, its role in regulating adipose tissue inflammation is unexplored. This study was designed to identify xanthones from G.mangostana, which could ameliorate adipose tissue inflammation.EXPERIMENTAL APPROACHExpressions of inducible NOS, cytokines, chemokines and components of the NF-kappa B and MAPKs pathways were evaluated using Western blotting, immunofluorescence, quantitative real-time PCR or ELISA. The migration of macrophages towards adipocytes was tested using Transwell experiments in vitro. A murine model of LPS-induced acute inflammation was used to examine effects of 1,3,6,7-tetrahydroxy-8-prenylxanthone (TPX) on inflammatory responses in adipose tissue in vivo.KEY RESULTSFrom a series of xanthones isolated from G.mangostana, TPX was identified as a potent inhibitor of LPS-induced NO production and IL-6 secretion in RAW264.7 macrophages. TPX ameliorated LPS-induced inflammatory responses in RAW264.7 macrophages, and TNF-alpha mediated inflammation in 3T3-L1 adipocytes, through inhibiting MAPKs and NF-kappa B activation and promoting sirtuin 3 expression. TPX also blocked RAW264.7 macrophages migration towards 3T3-L1 adipocytes in co-cultures. Furthermore, TPX alleviated LPS-induced adipose tissue inflammation in vivo by reducing pro-inflammatory cytokines and preventing the pro-inflammatory polarization of macrophages.CONCLUSIONS AND IMPLICATIONSTaken together, our results indicate that TPX disrupts the inflammatory responses between macrophages and adipocytes, and attenuates adipose tissue inflammation.