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FPR2-based anti-inflammatory and anti-lipogenesis activities of novel meroterpenoid dimers from Ganoderma
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2021-09-08 , DOI: 10.1016/j.bioorg.2021.105338
Xing-Rong Peng 1 , Qian Wang 2 , Hui-Rong Wang 3 , Kun Hu 1 , Wen-Yong Xiong 1 , Ming-Hua Qiu 1
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Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (14) with an unprecedented spiro[furo[3,2–b]benzofuran-3,2′-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, 13C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC50 value of 7.93 μM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 μM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-β (C/EBP-β), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation.



中文翻译:

灵芝新型类萜二聚体基于 FPR2 的抗炎和抗脂肪生成活性

四对新颖meroterpenoid二聚体,(±)-applandimeric酸AD(的1 - 4)以前所未有的螺[呋喃并[3,2- b ]苯并呋喃-3,2'-茚]芯从子实体中分离灵芝扁桃体。它们的平面结构是通过广泛的光谱分析明确确定的。它们的相对和绝对构型通过计算的核间距离、耦合常数、具有 DP4 + 分析的13 C NMR 和电子圆二色性 (ECD)得到证实。此外,基于分子对接的方法用于评估它们与与炎症相关的甲酰肽受体 2 (FPR2) 的相互作用。有趣的是,(±)-applandimeric 酸 D ( 4) 可以通过一些关键的氢键与 FPR2 键合。此外,体外生物测定证实4可以抑制FPR2的表达,IC 50值为7.93 μM。此外,与阳性对照 LiCl (20 mM) 相比,4在 20 μM 的浓度下显示出相当的抗脂肪生成活性。同时,4可以抑制过氧化物酶体增殖物激活受体的蛋白水平γ(PPAR- γ),CCAAT /增强子结合蛋白β(C / EBP- β)、脂肪细胞脂肪酸结合蛋白 4 (FABP4) 和脂肪酸合酶 (FAS) 通过激活 AMP 活化蛋白激酶 (AMPK) 信号通路。因此,我们的研究结果表明,化合物4可能是通过抑制脂肪细胞中的脂质积累和减轻炎症来治疗肥胖和肥胖相关疾病的先导化合物。

更新日期:2021-09-12
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